We checked 7 multidisciplinary journals on Friday, March 28, 2025 using the Crossref API. For the period March 21 to March 27, we retrieved 30 new paper(s) in 7 journal(s).

Annals of the American Academy of Political and Social Science

A Long Battle: Turkey’s Backsliding and Resistance Through Trench Warfare
Murat Somer
Full text
Since 2002, governments led by Recep Tayyip Erdoğan and his party have taken Turkey’s political regime from electoral democracy to electoral autocracy. This has been principally accomplished through legislative capture: control, abuse, and weaponization of Parliament to pass democracy-eroding laws, discredit opposition, and legitimize executive authoritarianism. But other tools, such as executive power grabs, were also used against strong state institutions, civil society, and even by Erdoğan against his own party. Democratic backsliding advanced through crises that polarized the electorate and through fierce political warfare between the incumbent government and its opponents. Like other cases on the legislative capture pathway, opposition parties have resisted backsliding predominantly through electoral mobilization, but their partial access to the legislature has, for the most part, limited their capacity to join forces with grassroots contentious politics. The opposition has not developed solutions for programmatic renewal that might heal formative rifts and lead to sustainable recovery.
Legislative Capture in Hungary: Well-Managed Autocratization
Zsolt Enyedi, BĂĄlint Mikola
Full text
We discuss the case of Hungary’s rapid democratic backsliding under Viktor Orbán as an example of legislative capture. We show that, despite relatively unfavorable conditions for autocratization, Viktor Orbán and his Fidesz party have supervised a well-crafted project of institutional transformation and a comprehensive regrouping of financial resources, all of which have led to an effective and stable concentration of power. This power concentration has its limits, given the country’s membership in the European Union, resistance by parts of the judiciary, media initiatives focused on corruption, and local opposition victories; but the national government’s room for maneuver has increased every year since 2010. We provide an overview of the changes that facilitated democratic erosion and an inventory of the actors that still retain a capacity to hinder further autocratization.
Democratic Backsliding Through Legislative Capture in Serbia: A One-Man Show
Filip Milačić
Full text
Serbia’s democracy has been in a state of continuous erosion since the Serbian Progressive Party and Aleksandar Vučić came to power in 2012. Vučić exploited his popularity as a self-proclaimed defender of the Serbian nation to gain full control of the party and initiate democratic backsliding through “legislative capture.” Vučić’s capture of the parliament and its appointment powers made possible a subsequent capture of many democratic institutions. The rest, mindful of Vučić’s broad electoral appeal, deferred to the executive. Challenges to Serbia’s democratic backsliding were attempted through popular mobilizations and electoral resistance, but they have not been successful. There are several reasons for such an outcome: the uneven playing field, a fragmented and ideologically heterogeneous opposition, a misguided choice of resistance strategies, the absence of an alternative political platform that addressed the issue of Kosovo—the antecedent condition that precipitated backsliding, and insufficient support from external prodemocracy actors.
Elite Collusion and Creeping Authoritarianism in Nicaragua: Lessons on Democratic Backsliding from an Outlier Case
Shelley A. McConnell
Full text
Nicaragua has followed an unusual path from democracy to authoritarianism. In 2000, despite deep political polarization, outgoing Liberal president Arnoldo Alemán colluded with opposition leader Daniel Ortega to convert politically neutral judicial and electoral institutions into partisan tools. Their pact constrained the party system and lowered the electoral threshold, enabling Ortega to win the presidency in 2006. From a minority position in the legislature, Ortega’s Sandinista National Liberation Front (FSLN) party used the politicized judiciary and electoral infrastructure to remove presidential term limits and manipulate elections. After gaining a legislative majority, the FSLN then reformed the constitution to consolidate power. Public resistance to democratic decline came slowly and too late: Initially offset by social spending funded in part by international authoritarian allies, it was ultimately repressed. The Nicaragua case shows that a gradualist pathway toward democratic backsliding may be available to minority parties in poor countries.
The Coalition Against Democratic Backsliding in Bolsonaro’s Brazil
Matias Spektor
Full text
This case study explores democratic backsliding in Brazil that was accompanied by Jair Bolsonaro’s rise to power and his push for autocratization. Bolsonaro’s presidency was characterized by systematic attacks on democratic institutions, including efforts to undermine the judiciary, the legislature, and electoral integrity. A broad prodemocracy coalition of political parties, state governors, civil society, and the judiciary emerged to resist Bolsonaro’s authoritarian drive. The coalition played a pivotal role in preserving Brazil's democratic framework and preventing further erosion of democratic norms, but structural weaknesses in Brazil’s political system—which include growing affective polarization, ineffective governance, and the creeping influence of organized crime—present significant challenges to sustaining democracy. In the face of these enduring threats, maintaining democratic resilience in Brazil will likely be difficult.
Plebiscitary Override in Venezuela: Erosion of Democracy and Deepening Authoritarianism
Laura Gamboa
Full text
Until the 1990s, Venezuela had one of the longest-running democracies in Latin America. Today it is one of the region’s most entrenched authoritarian regimes. I discuss Venezuela’s 25-year autocratization process, focusing on the contingent nature of democratic backsliding. This article is useful to understand how executive power grabs shape the ways in which those who oppose autocrats act to protect a democracy, as well as how the opposition can jeopardize, protect, and open spaces for democratic contestation in both democratic and authoritarian contexts.
Elite Collusion in Indonesia: How It Has Both Enabled and Limited Executive Aggrandizement
Marcus Mietzner
Full text
After a largely successful post-authoritarian transition, Indonesia has experienced democratic backsliding since the 2010s. This backsliding accelerated under the presidency of Joko Widodo (2014-2024), but it has not yet pushed the Indonesian polity into a full-blown autocracy. I argue that Indonesia’s specific pathway to democratic backsliding prefigured this outcome. While elites have colluded to share power and allow the president to engage in executive aggrandizement, they have set limits to the latter’s potential authoritarian ambitions. For example, they rejected Widodo’s attempt to extend his time in power beyond the constitutionally allowed two terms. Thus, elites have both produced executive aggrandizement and contained its scope. This pattern has protected Indonesian democracy from a full collapse, but it has produced a gradual decline, reducing the chances of democratic revitalization through formal or contentious politics.
Backsliding by Elite Collusion: Authoritarianism and Democratic Resurgence in Guatemala
Manuel Meléndez-Sånchez, Lucas Perelló
Full text
Guatemala is a case study in democratic backsliding led not by an aggrandized executive, but by a coalition of elites who collude to maximize and protect their collective power. Beginning in the mid-2010s, a decentralized but deeply entrenched network of elites dismantled democracy when anticorruption efforts threatened their common interests. The 2023 election was widely expected to consolidate this authoritarian turn but, instead, delivered an unexpected democratic resurgence when a moderate anticorruption reformer secured a shocking victory and then successfully resisted a “slow-motion coup” aimed at preventing the transfer of power. The Guatemalan case suggests that, under elite collusion, elites can be more prone to splits and strategic errors than in other authoritarian settings. These missteps provide unexpected opportunities to reverse backsliding, but democrats must be prepared to capitalize on regime errors and repel authoritarian counteroffensives by building broad coalitions that work simultaneously across multiple arenas of democratic contestation.
Legislative Capture and Democratic Careening in Poland
Hubert Tworzecki
Full text
“Democratic careening” aptly captures Poland’s recent oscillation between liberal democracy, illiberalism, and efforts toward the recovery of liberal democratic norms. In contrast to the recent experience of Hungary, Poland’s hard right governing party was unable to amend the nation’s constitution as it attempted to consolidate power, so it relied on ordinary legislation and changes of personnel in the judiciary and other state institutions. This analysis shows how Poland’s complex constitutional framework, its elections, and the contentious politics of resistance contributed to the nation’s democratic resilience. I also reflect on the challenges faced by Poland’s new government in undoing illiberal changes while avoiding legal and political instability, highlighting the broader implications of this case for democratic theory and the study of illiberalism.
Legislative Capture in India: Is Democracy Back from the Brink?
Milan Vaishnav
Full text
The Bharatiya Janata Party (BJP) won consecutive parliamentary majorities in India’s 2014 and 2019 elections, ushering in a period of single-party dominance that has replaced a quarter-century of coalition politics. This new era has been marked by a growing concentration of executive power, crackdowns on dissent, and rising Hindu majoritarianism. The roots of India’s democratic backsliding predate the BJP’s resurgence, but the trends have intensified in the past 10 years. While the party’s disappointing performance in the 2024 elections suggests a possible corrective, legislative capture in India will not easily unravel: The BJP remains in a commanding political position and shows little inclination toward moderation; questions about electoral integrity abound; referee institutions are abdicating their authority; and constraints on civil society endure. Given India’s outsize geopolitical importance, foreign pressure is unlikely to be decisive in reversing these trends.
Pathways of Democratic Backsliding, Resistance, and (Partial) Recoveries
Rachel Beatty Riedl, Jennifer McCoy, Kenneth Roberts, Murat Somer
Full text
We provide an analytical framework that identifies three distinct institutional pathways for democratic backsliding that culminate in executive aggrandizement: legislative capture, plebiscitary override, and executive power grabs. We also identify a fourth pathway of elite collusion that erodes democracy without necessarily concentrating powers in the executive. These four pathways reflect different combinations of ruling and opposition party strength, institutional legitimacy, and levels of popular support and political mobilization. The pathways also open and close different institutional and societal arenas where opposition forces can counter backsliding, and they create different opportunities, challenges, and dilemmas for democratic actors. The 15 case studies featured in this volume illustrate how backsliding occurs along these pathways, and how democratic actors achieved partial reversal in some cases. The cases also suggest focal points of resistance and institutional and programmatic reform that may be helpful to policymakers and advocates working to defend democracy.
Why Resistance to the Executive Power Grab in Tunisia Is Failing
Alexandra Domike Blackman
Full text
Kais Saied’s July 2021 power grab in Tunisia is a clear case of democratic backsliding, and the nation’s judiciary, political parties, and civil society organizations have been unable to slow the democratic erosion that is occurring under the Saied regime. I describe the political resistance to backsliding and why it has failed to date, analyzing the roles of specific institutions and individual actors in that resistance. I argue that two key dynamics explain why efforts to mobilize against Saied’s power grab have failed to slow democratic erosion in Tunisia: top-down regime control of key government institutions and a deep popular frustration with the country’s political class, which limited bottom-up mobilization against Saied’s power grab.
A Tale of a Failed Recovery: Ecuador’s Democratic Stagnation
Paolo Moncagatta, Mateo Pazmiño
Full text
Ecuador experienced a dramatic process of democratic backsliding during Rafael Correa’s decade-long administration, which began in 2007. The Correa administration brought plebiscitary overrides and constitutional reengineering that made the government a hyperpresidential one, weakening political institutions and undermining basic civil liberties. When Correa left power in 2017, Ecuador’s democracy recovered; but, even with the promise of an enduring democratic future, the country has not been able to consolidate a functioning representative democratic regime, and new processes of backsliding have occurred. A combination of weak political institutions, poor democratic culture, and major threats to political stability—including the infiltration of organized crime into the political arena—seems to have stagnated Ecuador at the status of a low-quality delegative democracy.
Elite Collusion and Dismantling Democracy in Benin
Dominika Koter
Full text
After 25 years of successful experience with democracy, Benin entered a phase of democratic backsliding after President Patrice Talon came to power in 2016. According to multiple measures, Benin’s democracy declined continuously between 2016 and 2023. This article highlights how the complacency and weakness of elites in Benin created an environment in which democracy deteriorated. Notably, the influence—or lack of influence—of elites resulted in limited competitiveness of the electoral process and worsening freedom of expression and assembly. Better cooperation of opposition forces in 2023 has helped to halt further backsliding, but it has not reversed the decline.
Lessons About Backsliding and Resistance
Thomas Carothers
Full text
International policymakers and those who provide assistance for the development and stabilization of democracies worldwide have often been slow to recognize and respond to democratic backsliding. Drawing from the case studies in this volume, I identify a set of policy-relevant lessons about processes of democratic backsliding, patterns of prodemocratic resistance, and the role of international actors.
Resisting Executive Power Grabs: Lessons from Malawi
Kim Yi Dionne, Boniface Dulani
Full text
We examine how Malawi’s presidents have attempted to undermine the nation’s democracy between 2000 and 2022, analyzing the ways in which key institutions and actors have resisted executive overreach and power grabs. After a long history of authoritarian rule, Malawi’s 1994 constitution envisioned a robust separation of powers, yet power remains concentrated in the presidency. Presidents have repeatedly attempted to consolidate power but have been rebuffed at crucial moments. Presidents have attempted to constrain political opposition through personalist ties, the bureaucracy, control over executive appointments, regulation, and coercion. But the courts and civil society have been key actors in countering executive overreach, exemplified by the Constitutional Court’s annulment of the 2019 presidential election. Despite recent legal reforms, Malawi’s parliament, opposition parties, and other political institutions still struggle to check the executive.
Legislative Capture and Oligarchic Collusion: Two Pathways of Democratic Backsliding and Recovery in Moldova
Ion Marandici
Full text
I examine two pathways of democratic backsliding in Moldova and the ways in which the country was able to reverse the backsliding trends. The first episode (2001–2009) started with a political party gaining a supermajority in Parliament and setting up a semi-authoritarian system of governance. Prodemocracy protests and coercive attempts by the state to suppress them led to an institutional stalemate, culminating in snap elections that brought a victory for the political opposition. The second backsliding episode (2014–2019) was characterized by oligarchic collusion: Major oligarchs funded and controlled the ruling parties while engaging in grand corruption and contributing to a gradual democratic decline. Recovery from this backsliding episode was enabled by cross-ethnic, transideological protests against corruption, strategic institutional changes, and interoligarchic wars. The analysis underscores how contentious politics, electoral processes, and the empowerment of weakened political institutions can help generate democratic recovery.

Nature

GPT-4o mini: Non-social science research article
Author Correction: Heritable polygenic editing: the next frontier in genomic medicine?
Peter M. Visscher, Christopher Gyngell, Loic Yengo, Julian Savulescu
Full text
GPT-4o mini: Non-social science research article
Publisher Correction: A metagenomic ‘dark matter’ enzyme catalyses oxidative cellulose conversion
Clelton A. Santos, Mariana A. B. Morais, Fernanda Mandelli, Evandro A. Lima, Renan Y. Miyamoto, Paula M. R. Higasi, Evandro A. Araujo, Douglas A. A. PaixĂŁo, Joaquim M. Junior, Maria L. Motta, Rodrigo S. A. Streit, Luana G. MorĂŁo, Claudio B. C. Silva, Lucia D. Wolf, Cesar R. F. Terrasan, Nathalia R. Bulka, Jose A. Diogo, Felipe J. Fuzita, Felippe M. Colombari, Camila R. Santos, Priscila T. Rodrigues, Daiane B. Silva, Sacha Grisel, Juliana S. Bernardes, Nicolas Terrapon, Vincent Lombard, Antonio J. C. Filho, Bernard Henrissat, Bastien Bissaro, Jean-Guy Berrin, Gabriela F. Persinoti, Mario T. Murakami
Full text
GPT-4o mini: Non-social science research article
Author Correction: AI models collapse when trained on recursively generated data
Ilia Shumailov, Zakhar Shumaylov, Yiren Zhao, Nicolas Papernot, Ross Anderson, Yarin Gal
Full text
GPT-4o mini: Non-social science research article
Certified randomness using a trapped-ion quantum processor
Minzhao Liu, Ruslan Shaydulin, Pradeep Niroula, Matthew DeCross, Shih-Han Hung, Wen Yu Kon, Enrique Cervero-MartĂ­n, Kaushik Chakraborty, Omar Amer, Scott Aaronson, Atithi Acharya, Yuri Alexeev, K. Jordan Berg, Shouvanik Chakrabarti, Florian J. Curchod, Joan M. Dreiling, Neal Erickson, Cameron Foltz, Michael Foss-Feig, David Hayes, Travis S. Humble, Niraj Kumar, Jeffrey Larson, Danylo Lykov, Michael Mills, Steven A. Moses, Brian Neyenhuis, Shaltiel Eloul, Peter Siegfried, James Walker, Charles Lim, Marco Pistoia
Full text
Although quantum computers can perform a wide range of practically important tasks beyond the abilities of classical computers 1,2 , realizing this potential remains a challenge. An example is to use an untrusted remote device to generate random bits that can be certified to contain a certain amount of entropy 3 . Certified randomness has many applications but is impossible to achieve solely by classical computation. Here we demonstrate the generation of certifiably random bits using the 56-qubit Quantinuum H2-1 trapped-ion quantum computer accessed over the Internet. Our protocol leverages the classical hardness of recent random circuit sampling demonstrations 4,5 : a client generates quantum ‘challenge’ circuits using a small randomness seed, sends them to an untrusted quantum server to execute and verifies the results of the server. We analyse the security of our protocol against a restricted class of realistic near-term adversaries. Using classical verification with measured combined sustained performance of 1.1 × 10 18 floating-point operations per second across multiple supercomputers, we certify 71,313 bits of entropy under this restricted adversary and additional assumptions. Our results demonstrate a step towards the practical applicability of present-day quantum computers.
GPT-4o mini: Non-social science research article
Plasticity of the mammalian integrated stress response
Chien-Wen Chen, David Papadopoli, Krzysztof J. Szkop, Bo-Jhih Guan, Mohammed Alzahrani, Jing Wu, Raul Jobava, Mais M. Asraf, Dawid Krokowski, Anastasios Vourekas, William C. Merrick, Anton A. Komar, Antonis E. Koromilas, Myriam Gorospe, Matthew J. Payea, Fangfang Wang, Benjamin L. L. Clayton, Paul J. Tesar, Ashleigh Schaffer, Alexander Miron, Ilya Bederman, Eckhard Jankowsky, Christine Vogel, LeoĆĄ Shivaya ValĂĄĆĄek, Jonathan D. Dinman, Youwei Zhang, Boaz Tirosh, Ola Larsson, Ivan Topisirovic, Maria Hatzoglou
Full text
GPT-4o mini: Non-social science research article
A prospective code for value in the serotonin system
Emerson F. Harkin, Cooper D. Grossman, Jeremiah Y. Cohen, Jean-Claude BĂ©ĂŻque, Richard Naud
Full text
GPT-4o mini: Non-social science research article
A coronavirus assembly inhibitor that targets the viral membrane protein
Manon Laporte, Dirk Jochmans, Dorothée Bardiot, Lowiese Desmarets, Oliver J. Debski-Antoniak, Giulia Mizzon, Rana Abdelnabi, Pieter Leyssen, Winston Chiu, Zhikuan Zhang, Norimichi Nomura, Sandro Boland, Umeharu Ohto, Yannick Stahl, Jurgen Wuyts, Steven De Jonghe, Annelies Stevaert, Martijn J. van Hemert, Brenda W. Bontes, Patrick Wanningen, G. J. Mirjam Groenewold, Aneta Zegar, Katarzyna Owczarek, Sanjata Joshi, Mohamed Koukni, Philippe Arzel, Hugo Klaassen, Jean-Christophe Vanherck, Ilse Vandecaetsbeek, Niels Cremers, Kim Donckers, Thibault Francken, Tina Van Buyten, Jasper Rymenants, Joost Schepers, Krzysztof Pyrc, Rolf Hilgenfeld, Jean Dubuisson, Berend-Jan Bosch, Frank Van Kuppeveld, Cecilia Eydoux, Etienne Decroly, Bruno Canard, Lieve Naesens, Birgit Weynand, Eric J. Snijder, Sandrine Belouzard, Toshiyuki Shimizu, Ralf Bartenschlager, Daniel L. Hurdiss, Arnaud Marchand, Patrick Chaltin, Johan Neyts
Full text
GPT-4o mini: Non-social science research article
Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3
Kelvin Y. Chen, Tatsuya Kibayashi, Ambre Giguelay, Mayu Hata, Shunsuke Nakajima, Norihisa Mikami, Yusuke Takeshima, Kenji Ichiyama, Ryusuke Omiya, Leif S. Ludwig, Kunihiro Hattori, Shimon Sakaguchi
Full text
GPT-4o mini: Non-social science research article
A small-molecule SARS-CoV-2 inhibitor targeting the membrane protein
Ellen Van Damme, Pravien Abeywickrema, Yanting Yin, Jiexiong Xie, Sofie Jacobs, Mandeep Kaur Mann, Jordi Doijen, Robyn Miller, Madison Piassek, Simone Marsili, Murali Subramanian, Leah Gottlieb, Rana Abdelnabi, Michiel Van Gool, Nick Van den Broeck, Ines De Pauw, Annick Diels, Peter Vermeulen, Koen Temmerman, Trevor Scobey, Melissa Mattocks, Alexandra SchÀfer, Dirk Jochmans, Steven De Jonghe, Pieter Leyssen, Winston Chiu, Mayra Diosa Toro, Marleen Zwaagstra, Anouk A. Leijs, Heidi L. M. De Gruyter, Christophe Buyck, Klaas Van Den Heede, Frank Jacobs, Christel Van den Eynde, Laura Thijs, Valerie Raeymaekers, Seth Miller, Amanda Del Rosario, Johan Neyts, Danielle Peeters, Ralph S. Baric, Frank J. M. van Kuppeveld, Eric J. Snijder, Martijn J. van Hemert, Mario Monshouwer, Sujata Sharma, Ruxandra Draghia-Akli, Anil Koul, Marnix Van Loock
Full text
The membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly 1,2 . Here we describe the identification of JNJ-9676, a small-molecule inhibitor targeting the coronavirus M protein. JNJ-9676 demonstrates in vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV and sarbecovirus strains from bat and pangolin zoonotic origin. Using cryogenic electron microscopy (cryo-EM), we determined a binding pocket of JNJ-9676 formed by the transmembrane domains of the M protein dimer. Compound binding stabilized the M protein dimer in an altered conformational state between its long and short forms, preventing the release of infectious virus. In a pre-exposure Syrian golden hamster model, JNJ-9676 (25 mg per kg twice per day) showed excellent efficacy, illustrated by a significant reduction in viral load and infectious virus in the lung by 3.5 and 4 log 10 -transformed RNA copies and 50% tissue culture infective dose (TCID 50 ) per mg lung, respectively. Histopathology scores at this dose were reduced to the baseline. In a post-exposure hamster model, JNJ-9676 was efficacious at 75 mg per kg twice per day even when added at 48 h after infection, when peak viral loads were observed. The M protein is an attractive antiviral target to block coronavirus replication, and JNJ-9676 represents an interesting chemical series towards identifying clinical candidates addressing the current and future coronavirus pandemics.
GPT-4o mini: Non-social science research article
Gene-modified pig-to-human liver xenotransplantation
Kai-Shan Tao, Zhao-Xu Yang, Xuan Zhang, Hong-Tao Zhang, Shu-Qiang Yue, Yan-Ling Yang, Wen-Jie Song, De-Sheng Wang, Zheng-Cai Liu, Hai-Min Li, Yong Chen, Rui Ding, Shi-Ren Sun, Ming Yu, Ji-Peng Li, Wei-Xun Duan, Zhe Wang, Jing-Wen Wang, Jia-Yun Liu, Min-Wen Zheng, Xi-Jing Zhang, Wen Yin, Wei-Jun Qin, Dong-Mei Bian, Lin Li, Min Li, Zhi-Bin Lin, Hao Xu, Dan Wei, Hong Zhang, Juan-Li Duan, Deng-Ke Pan, Hai-Long Dong, Lin Wang, Ke-Feng Dou
Full text
GPT-4o mini: Non-social science research article
Witnessing the onset of reionization through Lyman-α emission at redshift 13
Joris Witstok, Peter Jakobsen, Roberto Maiolino, Jakob M. Helton, Benjamin D. Johnson, Brant E. Robertson, Sandro Tacchella, Alex J. Cameron, Renske Smit, Andrew J. Bunker, Aayush Saxena, Fengwu Sun, Stacey Alberts, Santiago Arribas, William M. Baker, Rachana Bhatawdekar, Kristan Boyett, Phillip A. Cargile, Stefano Carniani, StĂ©phane Charlot, Jacopo Chevallard, Mirko Curti, Emma Curtis-Lake, Francesco D’Eugenio, Daniel J. Eisenstein, Kevin N. Hainline, Gareth C. Jones, Nimisha Kumari, Michael V. Maseda, Pablo G. PĂ©rez-GonzĂĄlez, Pierluigi Rinaldi, Jan Scholtz, Hannah Übler, Christina C. Williams, Christopher N. A. Willmer, Chris Willott, Yongda Zhu
Full text
Cosmic reionization began when ultraviolet (UV) radiation produced in the first galaxies began illuminating the cold, neutral gas that filled the primordial Universe 1,2 . Recent James Webb Space Telescope (JWST) observations have shown that surprisingly UV-bright galaxies were in place beyond redshift z = 14, when the Universe was less than 300 Myr old 3–5 . Smooth turnovers of their UV continua have been interpreted as damping-wing absorption of Lyman-α (Ly-α), the principal hydrogen transition 6–9 . However, spectral signatures encoding crucial properties of these sources, such as their emergent radiation field, largely remain elusive. Here we report spectroscopy from the JWST Advanced Deep Extragalactic Survey (JADES 10 ) of a galaxy at redshift z = 13.0 that reveals a singular, bright emission line unambiguously identified as Ly-α, as well as a smooth turnover. We observe an equivalent width of EW Ly-α > 40 Å (rest frame), previously only seen at z < 9 where the intervening intergalactic medium becomes increasingly ionized 11 . Together with an extremely blue UV continuum, the unexpected Ly-α emission indicates that the galaxy is a prolific producer and leaker of ionizing photons. This suggests that massive, hot stars or an active galactic nucleus have created an early reionized region to prevent complete extinction of Ly-α, thus shedding new light on the nature of the earliest galaxies and the onset of reionization only 330 Myr after the Big Bang.
GPT-4o mini: Non-social science research article
The global human impact on biodiversity
François Keck, Tianna Peller, Roman Alther, CĂ©cilia Barouillet, Rosetta Blackman, Eric Capo, Teofana Chonova, Marjorie Couton, Lena Fehlinger, Dominik Kirschner, Mara KnĂŒsel, Lucile Muneret, Rebecca Oester, KĂĄlmĂĄn Tapolczai, Heng Zhang, Florian Altermatt
Full text
Human activities drive a wide range of environmental pressures, including habitat change, pollution and climate change, resulting in unprecedented effects on biodiversity 1,2 . However, despite decades of research, generalizations on the dimensions and extent of human impacts on biodiversity remain ambiguous. Mixed views persist on the trajectory of biodiversity at the local scale 3 and even more so on the biotic homogenization of biodiversity across space 4,5 . We compiled 2,133 publications covering 97,783 impacted and reference sites, creating an unparallelled dataset of 3,667 independent comparisons of biodiversity impacts across all main organismal groups, habitats and the five most predominant human pressures 1,6 . For all comparisons, we quantified three key measures of biodiversity to assess how these human pressures drive homogenization and shifts in composition of biological communities across space and changes in local diversity, respectively. We show that human pressures distinctly shift community composition and decrease local diversity across terrestrial, freshwater and marine ecosystems. Yet, contrary to long-standing expectations, there is no clear general homogenization of communities. Critically, the direction and magnitude of biodiversity changes vary across pressures, organisms and scales at which they are studied. Our exhaustive global analysis reveals the general impact and key mediating factors of human pressures on biodiversity and can benchmark conservation strategies.
GPT-4o mini: Non-social science research article
Synaptic and neural behaviours in a standard silicon transistor
Sebastian Pazos, Kaichen Zhu, Marco A. Villena, Osamah Alharbi, Wenwen Zheng, Yaqing Shen, Yue Yuan, Yue Ping, Mario Lanza
Full text
Hardware implementations of artificial neural networks (ANNs)—the most advanced of which are made of millions of electronic neurons interconnected by hundreds of millions of electronic synapses—have achieved higher energy efficiency than classical computers in some small-scale data-intensive computing tasks 1 . State-of-the-art neuromorphic computers, such as Intel’s Loihi 2 or IBM’s NorthPole 3 , implement ANNs using bio-inspired neuron- and synapse-mimicking circuits made of complementary metal–oxide–semiconductor (CMOS) transistors, at least 18 per neuron and six per synapse. Simplifying the structure and size of these two building blocks would enable the construction of more sophisticated, larger and more energy-efficient ANNs. Here we show that a single CMOS transistor can exhibit neural and synaptic behaviours if biased in a specific (unconventional) manner. By connecting one additional CMOS transistor in series, we build a versatile 2-transistor-cell that exhibits adjustable neuro-synaptic response (which we named neuro-synaptic random access memory cell, or NS-RAM cell). This electronic performance comes with a yield of 100% and an ultra-low device-to-device variability, owing to the maturity of the silicon CMOS platform used—no materials or devices alien to the CMOS process are required. These results represent a short-term solution for the implementation of efficient ANNs and an opportunity in terms of CMOS circuit design and optimization for artificial intelligence applications.
GPT-4o mini: Non-social science research article
Phosphate-enabled mechanochemical PFAS destruction for fluoride reuse
Long Yang, Zijun Chen, Christopher A. Goult, Thomas Schlatzer, Robert S. Paton, VĂ©ronique Gouverneur
Full text
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent, bioaccumulative and anthropogenic pollutants that have attracted the attention of the public and private sectors because of their adverse impact on human health 1 . Although various technologies have been deployed to degrade PFASs with a focus on non-polymeric functionalized compounds (perfluorooctanoic acid and perfluorooctanesulfonic acid) 2–4 , a general PFAS destruction method coupled with fluorine recovery for upcycling is highly desirable. Here we disclose a protocol that converts multiple classes of PFAS, including the fluoroplastics polytetrafluoroethylene and polyvinylidene fluoride, into high-value fluorochemicals. To achieve this, PFASs were reacted with potassium phosphate salts under solvent-free mechanochemical conditions, a mineralization process enabling fluorine recovery as KF and K 2 PO 3 F for fluorination chemistry. The phosphate salts can be recovered for reuse, implying no detrimental impact on the phosphorus cycle. Therefore, PFASs are not only destructible but can now contribute to a sustainable circular fluorine economy.
GPT-4o mini: Non-social science research article
A human brain map of mitochondrial respiratory capacity and diversity
Eugene V. Mosharov, Ayelet M. Rosenberg, Anna S. Monzel, Corey A. Osto, Linsey Stiles, Gorazd B. Rosoklija, Andrew J. Dwork, Snehal Bindra, Alex Junker, Ya Zhang, Masashi Fujita, Madeline B. Mariani, Mihran Bakalian, David Sulzer, Philip L. De Jager, Vilas Menon, Orian S. Shirihai, J. John Mann, Mark D. Underwood, Maura Boldrini, Michel Thiebaut de Schotten, Martin Picard
Full text
GPT-4o mini: Non-social science research article
Glutamate gating of AMPA-subtype iGluRs at physiological temperatures
Anish Kumar Mondal, Elisa Carrillo, Vasanthi Jayaraman, Edward C. Twomey
Full text
GPT-4o mini: Non-social science research article
The other climate crisis
Tiffany A. Shaw, Bjorn Stevens
Full text
GPT-4o mini: Non-social science research article
The P-loop NTPase RUVBL2 is a conserved clock component across eukaryotes
Meimei Liao, Yanqin Liu, Zhancong Xu, Mingxu Fang, Ziqing Yu, Yufan Cui, Zhengda Sun, Ran Huo, Jieyu Yang, Fusheng Huang, Mingming Liu, Qin Zhou, Xiaocui Song, Hui Han, She Chen, Xiaodong Xu, Ximing Qin, Qun He, Dapeng Ju, Tao Wang, Nirav Thakkar, Paul E. Hardin, Susan S. Golden, Eric Erquan Zhang
Full text
GPT-4o mini: Non-social science research article
A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome
Manoj Jangra, Dmitrii Y. Travin, Elena V. Aleksandrova, Manpreet Kaur, Lena Darwish, Kalinka Koteva, Dorota Klepacki, Wenliang Wang, Maya Tiffany, Akosiererem Sokaribo, Brian K. Coombes, Nora VĂĄzquez-Laslop, Yury S. Polikanov, Alexander S. Mankin, Gerard D. Wright
Full text
GPT-4o mini: Non-social science research article
Generalizing arene C−H alkylations by radical−radical cross-coupling
Johannes Großkopf, Chawanansaya Gopatta, Robert T. Martin, Alexander Haseloer, David W. C. MacMillan
Full text
GPT-4o mini: Non-social science research article
Changes in neurotensin signalling drive hedonic devaluation in obesity
Neta Gazit Shimoni, Amanda J. Tose, Charlotte Seng, Yihan Jin, Tamås Lukacsovich, Hongbin Yang, Jeroen P. H. Verharen, Christine Liu, Michael Tanios, Eric Hu, Jonathan Read, Lilly W. Tang, Byung Kook Lim, Lin Tian, Csaba Földy, Stephan Lammel
Full text
Calorie-rich foods, particularly those that are high in fat and sugar, evoke pleasure in both humans and animals 1 . However, prolonged consumption of such foods may reduce their hedonic value, potentially contributing to obesity 2–4 . Here we investigated this phenomenon in mice on a chronic high-fat diet (HFD). Although these mice preferred high-fat food over regular chow in their home cages, they showed reduced interest in calorie-rich foods in a no-effort setting. This paradoxical decrease in hedonic feeding has been reported previously 3–7 , but its neurobiological basis remains unclear. We found that in mice on regular diet, neurons in the lateral nucleus accumbens (NAcLat) projecting to the ventral tegmental area (VTA) encoded hedonic feeding behaviours. In HFD mice, this behaviour was reduced and uncoupled from neural activity. Optogenetic stimulation of the NAcLat→VTA pathway increased hedonic feeding in mice on regular diet but not in HFD mice, though this behaviour was restored when HFD mice returned to a regular diet. HFD mice exhibited reduced neurotensin expression and release in the NAcLat→VTA pathway. Furthermore, neurotensin knockout in the NAcLat and neurotensin receptor blockade in the VTA each abolished optogenetically induced hedonic feeding behaviour. Enhancing neurotensin signalling via overexpression normalized aspects of diet-induced obesity, including weight gain and hedonic feeding. Together, our findings identify a neural circuit mechanism that links the devaluation of hedonic foods with obesity.
GPT-4o mini: Non-social science research article
BRCA2 prevents PARPi-mediated PARP1 retention to protect RAD51 filaments
Sudipta Lahiri, George Hamilton, Gemma Moore, Liana Goehring, Tony T. Huang, Ryan B. Jensen, Eli Rothenberg
Full text
GPT-4o mini: Non-social science research article
Catalytic allylation of native hexoses and pentoses in water with indium
Tapas Adak, Travis Menard, Matthew Albritton, Federico Florit, Martin D. Burke, Klavs F. Jensen, Scott E. Denmark
Full text
GPT-4o mini: Non-social science research article
Solidification of Earth’s mantle led inevitably to a basal magma ocean
Charles-Édouard BoukarĂ©, James Badro, Henri Samuel
Full text
One of the main interpretations of deep-rooted geophysical structures in the mantle 1 is that they stem from the top-down solidification of the primitive basal magma ocean of Earth above the core 2–6 . However, it remains debated whether solids first formed at the bottom of the mantle, solidifying upward, or above the melts, solidifying downward. Here we show that gravitational segregation of dense, iron-rich melts from lighter, iron-poor solids drives mantle evolution, regardless of where melting curves and geotherms intersect. This process results in the accumulation of iron-oxide-rich melts above the core, forming a basal magma ocean. We numerically model mantle solidification using a new multiphase fluid dynamics approach that integrates melting phase relations and geochemical models. This enables estimating the compositional signature and spatial distribution of primordial geochemical reservoirs, which may be directly linked to the isotopic anomalies measured in Archean rocks 7–11 . We find that a substantial amount of solids is produced at the surface of the planet, not at depth, injecting geochemical signatures of shallow silicate fractionation in the deep mantle. This work could serve as a foundation for re-examining the intricate interplay between mantle dynamics, petrology and geochemistry during the first thousand million years of the evolution of rocky planets.
GPT-4o mini: Non-social science research article
The contribution of de novo coding mutations to meningomyelocele
Yoo-Jin Jiny Ha, Ashna Nisal, Isaac Tang, Chanjae Lee, Ishani Jhamb, Cassidy Wallace, Robyn Howarth, Sarah Schroeder, Keng loi Vong, Naomi Meave, Fiza Jiwani, Chelsea Barrows, Sangmoon Lee, Nan Jiang, Arzoo Patel, Krisha Bagga, Niyati Banka, Liana Friedman, Francisco A. Blanco, Seyoung Yu, Soeun Rhee, Hui Su Jeong, Isaac Plutzer, Michael B. Major, BĂ©atrice Benoit, Christian PoĂŒs, Caleb Heffner, Zoha Kibar, Gyang Markus Bot, Hope Northrup, Kit Sing Au, Madison Strain, Allison E. Ashley-Koch, Richard H. Finnell, Joan T. Le, Hal S. Meltzer, Camila Araujo, Helio R. Machado, Roger E. Stevenson, Anna Yurrita, Sara Mumtaz, Awais Ahmed, Mulazim Hussain Khara, Osvaldo M. Mutchinick, JosĂ© RamĂłn Medina-Bereciartu, Friedhelm Hildebrandt, Gia Melikishvili, Ahmed I. Marwan, Valeria Capra, Mahmoud M. Noureldeen, Aida M. S. Salem, Mahmoud Y. Issa, Maha S. Zaki, Libin Xu, Ji Eun Lee, Donghyuk Shin, Anna Alkelai, Alan R. Shuldiner, Stephen F. Kingsmore, Stephen A. Murray, Heon Yung Gee, W. Todd Miller, Kimberley F. Tolias, John B. Wallingford, character(0), Allison E. Ashley Koch, Hal S. Meltzer, Joan T. Le, Kit Sing Au, Philip J. Lupo, Camila AraĂșjo, Tony Magana, Caroline M. Kolvenbach, Shirlee Shril, Yukitoshi Takahashi, Hormos Salimi-Dafsari, H. Westley Phillips, Brian Hanak, BĂŒlent Kara, Ayfer Sakarya GĂŒneƟ, David D. Gonda, Salman Kirmani, Tinatin Tkemaladze, Sangwoo Kim, Joseph G. Gleeson
Full text
GPT-4o mini: Non-social science research article
Long-term impact and biological recovery in a deep-sea mining track
Daniel O. B. Jones, Maria Belen Arias, Loïc Van Audenhaege, Sabena Blackbird, Corie Boolukos, Guadalupe Bribiesca-Contreras, Jonathan T. Copley, Andrew Dale, Susan Evans, Bethany F. M. Fleming, Andrew R. Gates, Hannah Grant, Mark G. J. Hartl, Veerle A. I. Huvenne, Rachel M. Jeffreys, Pierre Josso, Lucas D. King, Erik Simon-Lledó, Tim Le Bas, Louisa Norman, Bryan O’Malley, Thomas Peacock, Tracy Shimmield, Eva C. D. Stewart, Andrew K. Sweetman, Catherine Wardell, Dmitry Aleynik, Adrian G. Glover
Full text
GPT-4o mini: Non-social science research article
Oxidation of retromer complex controls mitochondrial translation
Junbing Zhang, Md Yousuf Ali, Harrison Byron Chong, Pei-Chieh Tien, James Woods, Carolina Noble, Tristan VornbÀumen, Zehra Ordulu, Anthony P. Possemato, Stefan Harry, Jay Miguel Fonticella, Lina Fellah, Drew Harrison, Maolin Ge, Neha Khandelwal, Yingfei Huang, Maëva Chauvin, Anica Tamara Bischof, Grace Marie Hambelton, Magdy Farag Gohar, Siwen Zhang, MinGyu Choi, Sara Bouberhan, Esther Oliva, Mari Mino-Kenudson, Natalya N. Pavlova, Michael Lawrence, Justin F. Gainor, Sean A. Beausoleil, Nabeel Bardeesy, Raul Mostoslavsky, David Pépin, Christopher J. Ott, Brian Liau, Liron Bar-Peled
Full text
GPT-4o mini: Non-social science research article
Connectome-driven neural inventory of a complete visual system
Aljoscha Nern, Frank Loesche, Shin-ya Takemura, Laura E. Burnett, Marisa Dreher, Eyal Gruntman, Judith Hoeller, Gary B. Huang, MichaƂ Januszewski, Nathan C. Klapoetke, Sanna Koskela, Kit D. Longden, Zhiyuan Lu, Stephan Preibisch, Wei Qiu, Edward M. Rogers, Pavithraa Seenivasan, Arthur Zhao, John Bogovic, Brandon S. Canino, Jody Clements, Michael Cook, Samantha Finley-May, Miriam A. Flynn, Imran Hameed, Alexandra M. C. Fragniere, Kenneth J. Hayworth, Gary Patrick Hopkins, Philip M. Hubbard, William T. Katz, Julie Kovalyak, Shirley A. Lauchie, Meghan Leonard, Alanna Lohff, Charli A. Maldonado, Caroline Mooney, Nneoma Okeoma, Donald J. Olbris, Christopher Ordish, Tyler Paterson, Emily M. Phillips, Tobias Pietzsch, Jennifer Rivas Salinas, Patricia K. Rivlin, Philipp Schlegel, Ashley L. Scott, Louis A. Scuderi, Satoko Takemura, Iris Talebi, Alexander Thomson, Eric T. Trautman, Lowell Umayam, Claire Walsh, John J. Walsh, C. Shan Xu, Emily A. Yakal, Tansy Yang, Ting Zhao, Jan Funke, Reed George, Harald F. Hess, Gregory S. X. E. Jefferis, Christopher Knecht, Wyatt Korff, Stephen M. Plaza, Sandro Romani, Stephan Saalfeld, Louis K. Scheffer, Stuart Berg, Gerald M. Rubin, Michael B. Reiser
Full text
Vision provides animals with detailed information about their surroundings and conveys diverse features such as colour, form and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons. Consequently, from flies to humans, visual regions in the brain constitute half its volume. These visual regions often have marked structure–function relationships, with neurons organized along spatial maps and with shapes that directly relate to their roles in visual processing. More than a century of anatomical studies have catalogued in detail cell types in fly visual systems 1–3 , and parallel behavioural and physiological experiments have examined the visual capabilities of flies. To unravel the diversity of a complex visual system, careful mapping of the neural architecture matched to tools for targeted exploration of this circuitry is essential. Here we present a connectome of the right optic lobe from a male Drosophila melanogaster acquired using focused ion beam milling and scanning electron microscopy. We established a comprehensive inventory of the visual neurons and developed a computational framework to quantify their anatomy. Together, these data establish a basis for interpreting how the shapes of visual neurons relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity and expert curation, we classified the approximately 53,000 neurons into 732 types. These types are systematically described and about half are newly named. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron-type catalogue. Overall, this comprehensive set of tools and data unlocks new possibilities for systematic investigations of vision in Drosophila and provides a foundation for a deeper understanding of sensory processing.
GPT-4o mini: Non-social science research article
Deconstruction of rubber via C–H amination and aza-Cope rearrangement
Sydney E. Towell, Maxim Ratushnyy, Lauren S. Cooke, Geoffrey M. Lewis, Aleksandr V. Zhukhovitskiy
Full text
GPT-4o mini: Non-social science research article
irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA
Luca Ducoli, Brian J. Zarnegar, Douglas F. Porter, Robin M. Meyers, Weili Miao, Nicholas M. Riley, Suhas Srinivasan, Leandra V. Jackrazi, Yen-Yu Yang, Zhouxian Li, Yinsheng Wang, Carolyn R. Bertozzi, Ryan A. Flynn, Paul A. Khavari
Full text
GPT-4o mini: Non-social science research article
Macrophages harness hepatocyte glutamate to boost liver regeneration
María del Mar Rigual, Mariana Angulo-Aguado, Sladjana Zagorac, Ruth Álvarez-Díaz, Marta Benítez-Mondéjar, Fengming Yi, Carlos Martínez-Garay, Karla Santos-de-Frutos, Eunjeong Kim, Ramón Campos-Olivas, Nabil Djouder
Full text
GPT-4o mini: Non-social science research article
Multimodal generative AI for medical image interpretation
Vishwanatha M. Rao, Michael Hla, Michael Moor, Subathra Adithan, Stephen Kwak, Eric J. Topol, Pranav Rajpurkar
Full text
GPT-4o mini: Non-social science research article
MFSD6 is an entry receptor for enterovirus D68
Lauren Varanese, Lily Xu, Christine E. Peters, Grigore Pintilie, David S. Roberts, Suyash Raj, Mengying Liu, Yaw Shin Ooi, Jonathan Diep, Wenjie Qiao, Christopher M. Richards, Jeremy Callaway, Carolyn R. Bertozzi, Sabrina Jabs, Erik de Vries, Frank J. M. van Kuppeveld, Claude M. Nagamine, Wah Chiu, Jan E. Carette
Full text
GPT-4o mini: Non-social science research article
STING agonist-based ER-targeting molecules boost antigen cross-presentation
Xiafeng Wang, Zhangping Huang, Lixiao Xing, Liru Shang, Juan Jiang, Caiguanxi Deng, Wei Yu, Lin Peng, Hao Yang, Xiaohong Zheng, Xinmin Liu, Haolan Yang, Yixin Chen, Yongyong Li, Jing Liu, Xi Xie, Wei Xu, Xiaojun Xia, Zezhong Liu, Wanli Liu, Shibo Jiang, Yingyue Zeng, Lu Lu, Ji Wang
Full text
Nature DOI suffix ≠ "/s...": Not a research article
New lasso-shaped antibiotic kills drug-resistant bacteria
Benjamin Thompson, Shamini Bundell
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Lessons from Portugal on effects of cutting research funding
Marc Veldhoen, João T. Barata, Luisa M. Figueiredo, Claus M. Azzalin
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Ship-pollution cuts have an electrifying effect: less lightning at sea
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Ancient shackles testify to brutality of Egypt’s gold mines
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How to get more women into mining
Linqi Huang, Xibing Li, Longjun Dong, Haoxuan Yu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
First map of human brain mitochondria is ‘groundbreaking’ achievement
Nora Bradford
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Why is there more matter than antimatter? CERN result offers tantalizing new clue
Elizabeth Gibney
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Mice give unconscious friends first aid
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Shaking up earthquake safety in Nepal with a folk song
Saugat Bolakhe
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How marathons change runners’ brains: scans point to surprise energy source
Celeste Biever
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Live-cell super-resolution microscopy reveals how molecules enter and exit the nucleus
Bernd Rieger, Enya S. Berrevoets
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Babies make memories — so why don’t we recall them?
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Some assembly required
Russell Nichols
Full text
Nature DOI suffix ≠ "/s...": Not a research article
A superbug rose to the top after gaining a chemical weapon
Full text
Nature DOI suffix ≠ "/s...": Not a research article
AlphaFold is running out of data — so drug firms are building their own version
Ewen Callaway
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Why women are far more likely to develop Alzheimer’s than men
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Meet ‘qudits’: more complex cousins of qubits boost quantum computing
Davide Castelvecchi
Full text
Nature DOI suffix ≠ "/s...": Not a research article
What CERN does next matters for science and for international cooperation
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Microbes can capture carbon and degrade plastic — why aren’t we using them more?
Rino Rappuoli, Nguyen K. Nguyen, David E. Bloom, Charles Brooke, Rachel M. Burckhardt, Alan D. Dangour, Dilfuza Egamberdieva, Gigi K. Gronvall, Trevor D. Lawley, Jay T. Lennon, Ryan Morhard, Aindrila Mukhopadhyay, Raquel Peixoto, Pamela A. Silver, Lisa Y. Stein
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Global marine heatwave of 2023–24 was viewed as unlikely but not impossible given current warming
Full text
Nature DOI suffix ≠ "/s...": Not a research article
A lighthouse galaxy shines unexpectedly through the fog of the cosmic dawn
Michele Trenti
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Recovery of fluoride from ‘forever chemicals’ could lead to circular economy for fluorine
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Crucial meeting: molecule helps vaccine to interact with killer T cells
John T. Wilson
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Give grants to female scientists in war zones
Natalia Tsybuliak, Yana Suchikova
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Exclusive: NIH to cut grants for COVID research, documents reveal
Max Kozlov
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How to know whether a conference is right for you
Christine Ro
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Climate change will send home insurance spiralling. Here’s how to control costs
Scott St. George
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Life-giving oxygen is wafting out of lakes worldwide
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Paralysed man stands again after receiving ‘reprogrammed’ stem cells
Smriti Mallapaty
Full text
Nature DOI suffix ≠ "/s...": Not a research article
A map of mitochondrial biology reveals the energy landscape of the human brain
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Glaciers are not just blocks of ice — plans to save them mustn’t overlook their hidden life
Tom J. Battin, Albert van Wijngaarden, Birgit Sattler, Alexandre M. Anesio, Joseph Cook, Matthias Huss, Arwyn Edwards
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Winds on an ultrahot planet challenge climate models
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Does sharing first authorship on a paper carry a penalty? What the research says
Holly Else
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Track gender ratios in research to keep countries, institutions and publishers accountable
Full text
Nature DOI suffix ≠ "/s...": Not a research article
New antibiotic that kills drug-resistant bacteria discovered in technician’s garden
Smriti Mallapaty
Full text
Nature DOI suffix ≠ "/s...": Not a research article
NIH has cut one mRNA-vaccine grant. Will more follow?
Max Kozlov
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The full lethal impact of massive cuts to international food aid
Saskia Osendarp, Marie Ruel, Emorn Udomkesmalee, Masresha Tessema, Lawrence Haddad
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Fasting for weight loss is all the rage: what are the health benefits?
Nic Fleming
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: The mysterious force pushing galaxies apart might be getting weaker
Jacob Smith
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Reviving the biodiversity around an ancient palace
Ugo Mellone
Full text
Nature DOI suffix ≠ "/s...": Not a research article
‘Boggles the mind’: US defence department slashes research on emerging threats
Smriti Mallapaty
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The expanding Universe — do ongoing tensions leave room for new physics?
Wendy Freedman
Full text
Nature DOI suffix ≠ "/s...": Not a research article
RNA function follows form – why is it so hard to predict?
Diana Kwon
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Gender gap in research publishing is improving — slowly
Rachel Williamson
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Neuronal receptors at body temperature reveal their gating mechanics
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Empower families to lead the design of their ageing loved ones’ health care
Shahmir H. Ali
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Lasso-shaped molecule is a new type of broad-spectrum antibiotic
Lynn L. Silver
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Why Africans should be telling the story of human origins
Abdullahi Tsanni
Full text
Nature DOI suffix ≠ "/s...": Not a research article
‘Anxiety is palpable’: detention of researchers at US border spurs travel worries
Heidi Ledford, Alexandra Witze
Full text
Nature DOI suffix ≠ "/s...": Not a research article
‘All this is in crisis’: US universities curtail staff and spending as Trump cuts take hold
Smriti Mallapaty
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Drugs that target ‘zombie’ cells soothe an aching back
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How a scientist–pop industry partnership slashed a live gig’s carbon emissions by 98%
Esme Hedley
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Why is my cello howling?
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Lesotho matters
Nthabiseng Mokoena-Mokhali, Liteboho Senyane, Brian Stewart, Peter Mitchell
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Mathematician who reshaped theory of symmetry wins Abel Prize
Davide Castelvecchi
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Trump administration sued over huge funding cuts at Columbia University
Jeff Tollefson
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How the Atlantic jet stream has changed in 600 years — and what it means for weather
Matthew P. Dannenberg, Erika K. Wise
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Pregnancy’s true toll on the body: huge birth study paints most detailed picture yet
Celeste Biever
Full text
Nature DOI suffix ≠ "/s...": Not a research article
75% of US scientists who answered Nature poll consider leaving
Alexandra Witze
Full text

Nature Human Behaviour

GPT-4o mini: Non-social science research article
General anaesthesia decreases the uniqueness of brain functional connectivity across individuals and species
Andrea I. Luppi, Daniel Golkowski, Andreas Ranft, Rudiger Ilg, Denis Jordan, Danilo Bzdok, Adrian M. Owen, Lorina Naci, Emmanuel A. Stamatakis, Enrico Amico, Bratislav Misic
Full text
The human brain is characterized by idiosyncratic patterns of spontaneous thought, rendering each brain uniquely identifiable from its neural activity. However, deep general anaesthesia suppresses subjective experience. Does it also suppress what makes each brain unique? Here we used functional MRI scans acquired under the effects of the general anaesthetics sevoflurane and propofol to determine whether anaesthetic-induced unconsciousness diminishes the uniqueness of the human brain, both with respect to the brains of other individuals and the brains of another species. Using functional connectivity, we report that under anaesthesia individual brains become less self-similar and less distinguishable from each other. Loss of distinctiveness is highly organized: it co-localizes with the archetypal sensory–association axis, correlating with genetic and morphometric markers of phylogenetic differences between humans and other primates. This effect is more evident at greater anaesthetic depths, reproducible across sevoflurane and propofol and reversed upon recovery. Providing convergent evidence, we show that anaesthesia shifts the functional connectivity of the human brain closer to the functional connectivity of the macaque brain in a low-dimensional space. Finally, anaesthesia diminishes the match between spontaneous brain activity and cognitive brain patterns aggregated from the Neurosynth meta-analytic engine. Collectively, the present results reveal that anaesthetized human brains are not only less distinguishable from each other, but also less distinguishable from the brains of other primates, with specifically human-expanded regions being the most affected by anaesthesia.
The synergy of embodied cognition and cognitive load theory for optimized learning
Liye Zou, Zhihao Zhang, Myrto Mavilidi, Yanxia Chen, Fabian Herold, Kim Ouwehand, Fred Paas
Full text
Improving mobility data for infectious disease research
Natalya Kostandova, Ronan Corgel, Shweta Bansal, Sophie Bérubé, Eimear Cleary, Chelsea Hansen, Matt D. T. Hitchings, Bernardo García-Carreras, Lauren Gardner, Moritz U. G. Kraemer, Shengjie Lai, Yao Li, Amanda C. Perofsky, Giulia Pullano, Jonathan M. Read, Gabriel Ribeiro dos Santos, Henrik Salje, Saki Takahashi, Cécile Viboud, Jasmine Wang, Derek A. T. Cummings, Amy Wesolowski
Full text
Socio-economic status is a social construct with heritable components and genetic consequences
Abdel Abdellaoui, Hilary C. Martin, Martin Kolk, Adam Rutherford, Michael Muthukrishna, Felix C. Tropf, Melinda C. Mills, Brendan P. Zietsch, Karin J. H. Verweij, Peter M. Visscher
Full text

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Structural elucidation of how ARF small GTPases induce membrane tubulation for vesicle fission
Xiaoyun Pang, Yan Zhang, Kunyou Park, Zhenyu Liao, Jian Li, Jiashu Xu, Minh-Triet Hong, Guoliang Yin, Tongming Zhang, Yaoyu Wang, Edward H. Egelman, Jun Fan, Victor W. Hsu, Seung-Yeol Park, Fei Sun
Full text
ADP-Ribosylation Factor (ARF) small GTPases have been found to act in vesicle fission through a direct ability to tubulate membrane. We have pursued cryoelectron microscopy (EM) to reveal at 3.9 Å resolution how ARF6 assembles into a protein lattice on tubulated membrane. Molecular dynamics simulation studies confirm and extend the cryo-EM findings. The ARF6 lattice exhibits features that are distinct from those formed by other membrane-bending proteins. We identify protein contacts critical for lattice assembly and how membrane insertion results in constricted tubules. The lattice structure also enables docking by GTPase-activating proteins (GAP) to achieve vesiculation. We have also modeled ARF1 onto the ARF6 lattice, and then pursued vesicle reconstitution by the Coat Protein I (COPI) complex to further confirm that the ARF lattice acts in vesicle fission. By elucidating how an ARF protein tubulates membrane at the structural level, we have advanced the molecular understanding of how this class of transport factors promote the fission stage of vesicle formation.
GPT-4o mini: Non-social science research article
Pulsatile flow induces chromatin interaction with lamin-associated proteins to enrich H3K9 methylation in endothelial cells
Li-Jing Chen, Julie Yi-Shuan Li, Phu Nguyen, Gerard Norwich, Yingxiao Wang, Dayu Teng, Yan-Ting Shiu, John Y. J. Shyy, Shu Chien
Full text
Endothelial cells (ECs) are constantly exposed to hemodynamic forces, which play a crucial role in regulating EC functions. Pulsatile laminar shear stress (PS), representing atheroprotective flow, maintains the anti-inflammation and homeostatic phenotype of ECs, but the comprehensive mechanism underlying the PS-repression of inflammatory genes remains to be determined. In this study, we investigated the role of chromatin organization in mediating the effects of PS on inflammatory gene expression in ECs. We demonstrated that PS induced the expression of histone methyltransferase SUV39H1 to promote heterochromatin formation via H3K9 trimethylation (H3K9me3) enrichment, a hallmark gene repression mechanism. SUV39H1 interacts with lamin-associated proteins and facilitates the perinuclear localization of the H3K9me3-enrichment. Silencing the lamin-associated protein emerin (EMD) not only led to the reductions of cytoskeletal F-actin formation and perinuclear H3K9me3 enrichment; but also the impairment of PS-induced SUV39H1 expression, H3K9me3 enrichment at E-selectin and vascular cell adhesion molecule 1 loci to revert their PS-repressed expression. Hence, EMD acts as a hub to transmit mechanical cues from the cytoskeleton to the nucleus and recruits SUV39H1, which regulate nuclear organization, chromatin state, and gene expression. These results accentuate the critical role of nuclear architecture in mechanotransduction and EC responses to mechanical stimuli.
GPT-4o mini: Non-social science research article
Primitive homochiral polyester formation driven by tartaric acid and calcium availability
Chen Chen, Ruiqin Yi, Motoko Igisu, Rehana Afrin, Mahendran Sithamparam, Kuhan Chandru, Yuichiro Ueno, Linhao Sun, Tommaso Laurenzi, Ivano Eberini, Tommaso P. Fraccia, Anna Wang, H. James Cleaves, Tony Z. Jia
Full text
α-hydroxy acids (αHAs), simple and prebiotically plausible organic monomers, were likely present in various environments on and off Earth and could have played a role in directing the emergence of the first homochiral living systems. Some αHAs, which could have been of varying chirality, can undergo dehydration polymerization into polyesters, which could assemble into membraneless microdroplets upon rehydration; understanding these processes is critical for unraveling how simple prebiotic molecules transitioned into more complex systems capable of supporting selective chemical reactions, a key step toward the origin of life. Here, we focused on tartaric acid (TA), a prebiotically relevant αHA with multiple chiral forms, to probe plausible mechanisms by which primitive αHA and polyester-based systems could have participated in selective homochiral polymer synthesis. Enantiopure solutions of d -TA or l -TA polymerize efficiently via dehydration, while racemic dl -TA polymerization is inhibited due to stereochemical incompatibility. We found that Ca 2+ ions influence this process in two significant ways: 1) regulating TA monomer availability through selective crystallization, removing equal amounts of both enantiomers in racemic proportion and thereby enriching the enantiomeric excess of the remaining nonracemic TA solution; and 2) modulating polymerization by suppressing enantiopure TA polymerization while enabling dl -TA polymerization. These findings suggest that the differential availability of simple inorganic ions, such as Ca 2+ , could have indirectly mediated the selection of simple organic chiral monomers and the emergence of homochirality in primitive protocell-forming polymers, offering a pathway from nonliving to living matter in early Earth environments.
GPT-4o mini: Non-social science research article
Correction to Supporting Information for Walters et al., Identification of FSH-regulated and estrous stage–specific transcriptional networks in mouse ovaries
Full text
GPT-4o mini: Non-social science research article
Correction for Magesh et al., Co-zorbs: Motile, multispecies biofilms aid transport of diverse bacterial species
Full text
GPT-4o mini: Non-social science research article
BCFW tilings and cluster adjacency for the amplituhedron
Chaim Even-Zohar, Tsviqa Lakrec, Matteo Parisi, Melissa Sherman-Bennett, Ran Tessler, Lauren Williams
Full text
In 2005, Britto, Cachazo, Feng, and Witten gave a recurrence (now known as the BCFW recurrence) for computing scattering amplitudes in N = 4 super Yang–Mills theory. Arkani-Hamed and Trnka subsequently introduced the amplituhedron to give a geometric interpretation of the BCFW recurrence. Arkani-Hamed and Trnka conjectured that each way of iterating the BCFW recurrence gives a “triangulation” or “tiling” of the m=4 amplituhedron. In this article, we prove the BCFW tiling conjecture of Arkani-Hamed and Trnka. We also prove the cluster adjacency conjecture for BCFW tiles of the amplituhedron, which says that facets of tiles are cut out by collections of compatible cluster variables for the Grassmannian Gr4,n. Moreover we show that each BCFW tile is the subset of the Grassmannian where certain cluster variables have particular signs.
GPT-4o mini: Non-social science research article
Substrate specificities of two ketosynthases in eukaryotic microalgal and prokaryotic marine bacterial DHA synthases
Kaito Ogata, Riku Nakama, Hiyu Kobayashi, Tomoya Kawata, Chitose Maruyama, Takeshi Tsunoda, Tetsuro Ujihara, Yoshimitsu Hamano, Yasushi Ogasawara, Tohru Dairi
Full text
Highly reducing iterative polyketide synthases (HR-iPKSs) are huge enzyme complexes with multiple catalytic domains that biosynthesize polyketides by intrinsically programmed iterative carbon chain extensions and reductions. Unlike most HR-iPKSs, which possess a single ketosynthase (KS) domain for all carbon chain elongations, polyunsaturated fatty acid (PUFA) synthases contain two KS domains. We previously examined the substrate specificities of two KS domains of prokaryotic marine PUFA synthases with several acyl-ACP intermediates and showed that the two KS domains are utilized differentially depending on the carbon chain length. In this study, we investigated two KS domains in a eukaryotic microalgal DHA synthase, KS A and KS B , which show low similarities to those of prokaryotic marine enzymes, together with almost all the acyl-ACP intermediates. C6-, C12-, and C18-ACPs were exclusively accepted by KS A while KS B utilized C-8. C14- and C20-ACPs. In contrast, both KS A and KS B showed activities against C2-, C4-, and C10-ACPs. A general tendency was observed in which both the prokaryotic KS and the eukaryotic KS recognized the acyl structures in the vicinity of the thioester in ACP substrates except for short-chain substrates.
GPT-4o mini: Non-social science research article
Competition response of cloud supersaturation explains diminished Twomey effect for smoky aerosol in the tropical Atlantic
Jeramy L. Dedrick, Christian N. Pelayo, Lynn M. Russell, Dan Lubin, Johannes MĂŒlmenstĂ€dt, Mark Miller
Full text
The Twomey effect brightens clouds by increasing aerosol concentrations, which activates more droplets and decreases cloud supersaturation in response to more competition for water vapor. To quantify this competition response, we used marine low cloud observations in clean and smoky conditions at Ascension Island in the tropical South Atlantic during the Layered Aerosol Smoke Interactions with Cloud (LASIC) campaign. These observations show similar increases in droplet number for increased accumulation-mode particles from surface-based and satellite cloud retrievals, demonstrating the importance of below-cloud aerosol measurements for retrieving aerosol–cloud interactions (ACI) in clean and smoky aerosol conditions. Four methods for estimating cloud supersaturation from aerosol–cloud measurements were compared, with cloud scene-based and parcel-based methods showing sufficient variability for a strong dependence on both aerosol accumulation number concentration and cloud-base updraft velocities. Decomposing aerosol-related changes in cloud albedo and optical depth shows the calculated competition response accounts for dampening the activation response by 12 to 35%, explaining the diminished Twomey effect at high aerosol concentrations observed for smoky conditions at LASIC and previously around the world. This result was consistent for independent supersaturation retrievals by cloud scene-based droplet number and cloud condensation nuclei and parcel-based multimode size-resolving Lagrangian methods. Translating aerosol effects to local radiative forcing with clean conditions as a proxy for preindustrial and smoky conditions for present-day showed that the competition response reduces cooling from the Twomey radiative forcing by 12 to 35%, providing an essential process-specific constraint for improving the representation of aerosol competition in climate model simulation of indirect aerosol forcing.
GPT-4o mini: Non-social science research article
Lysosomal PIP 3 revealed by genetically encoded lipid biosensors
Ayse Z. Sahan, Mingyuan Chen, Qi Su, Qingrong Li, Dong Wang, Jin Zhang
Full text
3-Phosphoinositides (3-PIs), phosphatidylinositol (3,4) bisphosphate [PI(3,4)P 2 ] and phosphatidylinositol (3,4,5) trisphosphate (PIP 3 ), are important lipid second messengers in the Phosphoinositide 3-Kinase (PI3K)/Akt signaling pathway, which is crucial to cell growth and frequently dysregulated in cancer. Emerging evidence suggests these lipid second messengers may be present in membranes beyond the plasma membrane, yet their spatial regulation within other membrane compartments is not well understood. To dissect the spatial regulation of specific 3-PI species, we developed genetically encodable biosensors with selectivity for PIP 3 or PI(3,4)P 2 . Using these biosensors, we showed that PIP 3 significantly accumulated at the lysosome upon growth factor stimulation, in contrast to the conventional view that PIP 3 is exclusively present in the plasma membrane. Furthermore, we showed that lysosomal PIP 3 originates from the plasma membrane and relies on dynamin-dependent endocytosis for lipid internalization. Thus, PIP 3 can exploit dynamic trafficking pathways to access subcellular compartments and regulate signaling in a spatially selective manner.
GPT-4o mini: Non-social science research article
The visuomotor transformations underlying target-directed behavior
Peixiong Zhao, Yuxin Tong, Ivan P. Lazarte, Biswadeep Khan, Guangnan Tian, Kenny K. Y. Chen, Thomas K. C. Lam, Yu Hu, Julie L. Semmelhack
Full text
The visual system can process diverse stimuli and make the decision to execute appropriate behaviors, but it remains unclear where and how this transformation takes place. Innate visually evoked behaviors such as hunting, freezing, and escape are thought to be deeply conserved, and have been described in a range of species from insects to humans. We found that zebrafish larvae would respond to predator-like visual stimuli with immobility and bradycardia, both hallmarks of freezing, in a head-fixed behavioral paradigm. We then imaged the zebrafish visual system while larvae responded to different visual stimuli with hunting, freezing, and escape behaviors and systematically identified visually driven neurons and behaviorally correlated sensorimotor neurons. Our analyses indicate that within the optic tectum, broadly tuned sensory neurons are functionally correlated with sensorimotor neurons which respond specifically during one behavior, indicating that it contains suitable information for sensorimotor transformation. We also identified sensorimotor neurons in four other areas downstream of the tectum, and these neurons are also specific for one behavior, indicating that the segregation of the pathways continues in other areas. While our findings shed light on how sensorimotor neurons may integrate visual inputs, further investigation will be required to determine how sensorimotor neurons in different regions interact and where the decision to behave is made.
GPT-4o mini: Non-social science research article
Revealing the roles of the solid–electrolyte interphase in designing stable, fast-charging, low-temperature Li-ion batteries
Lei Tao, Hanrui Zhang, Sameep Rajubhai Shah, Xixian Yang, Jianwei Lai, Yanjun Guo, Joshua A. Russell, Dawei Xia, Jungki Min, Weibo Huang, Chenguang Shi, Zhaohui Liang, Deyang Yu, Sooyeon Hwang, Hui Xiong, Louis A. Madsen, Kejie Zhao, Feifei Shi, Feng Lin
Full text
Designing the solid–electrolyte interphase (SEI) is critical for stable, fast-charging, low-temperature Li-ion batteries. Fostering a “fluorinated interphase,” SEI enriched with LiF, has become a popular design strategy. Although LiF possesses low Li-ion conductivity, many studies have reported favorable battery performance with fluorinated SEIs. Such a contradiction suggests that optimizing SEI must extend beyond chemical composition design to consider spatial distributions of different chemical species. In this work, we demonstrate that the impact of a fluorinated SEI on battery performance should be evaluated on a case-by-case basis. Sufficiently passivating the anode surface without impeding Li-ion transport is key. We reveal that a fluorinated SEI containing excessive and dense LiF severely impedes Li-ion transport. In contrast, a fluorinated SEI with well-dispersed LiF (i.e., small LiF aggregates well mixed with other SEI components) is advantageous, presumably due to the enhanced Li-ion transport across heterointerfaces between LiF and other SEI components. An electrolyte, 1 M LiPF 6 in 2-methyl tetrahydrofuran (2MeTHF), yields a fluorinated SEI with dispersed LiF. This electrolyte allows anodes of graphite, ÎŒSi/graphite composite, and pure Si to all deliver a stable Coulombic efficiency of 99.9% and excellent rate capability at low temperatures. Pouch cells containing layered cathodes also demonstrate impressive cycling stability over 1,000 cycles and exceptional rate capability down to −20 °C. Through experiments and theoretical modeling, we have identified a balanced SEI-based approach that achieves stable, fast-charging, low-temperature Li-ion batteries.
GPT-4o mini: Non-social science research article
Targeted degradation of α-Synuclein using an evolved botulinum toxin protease
Philipp Sondermann, Christian S. Diercks, Cynthia Rong, Peter G. Schultz
Full text
There is considerable interest in the targeted degradation of proteins implicated in human disease. The use of sequence-specific proteases for this purpose is severely limited by the difficulty in engineering the numerous enzyme–substrate interactions required to yield highly selective proteases while maintaining catalytic activity. Herein, we report a strategy to evolve a protease for the programmed degradation of α-Synuclein, a presynaptic protein closely linked to Parkinson’s disease. Our structure-guided evolution campaign uses the protease from botulinum neurotoxin and showcases the stepwise change of specificity from its native substrate SNAP25 to the selective degradation of α-Synuclein. The protease’s selectivity is further demonstrated in human cells where near complete degradation of overexpressed human α-Synuclein is observed with no significant effects on cell proliferation. This stepwise strategy may serve as a general approach to evolve highly selective proteases targeting dysregulated proteins.
GPT-4o mini: Non-social science research article
Tetrapod species–area relationships across the Cretaceous–Paleogene mass extinction
Roger Adam Close, Bouwe Rutger Reijenga
Full text
Mass extinctions are rare but catastrophic events that profoundly disrupt biodiversity. Widely accepted consequences of mass extinctions, such as biodiversity loss and the appearance of temporary “disaster taxa,” imply that species–area relationships (SARs, or how biodiversity scales with area) should change dramatically across these events: Specifically, both the slope (the rate of accumulation of new species with increasing area) and intercept (the density of species at local scales) of the power–law relationship should decrease. However, these hypotheses have not been tested, and the contribution of variation in the SAR to diversity dynamics in deep time has been neglected. We use fossil data to quantify nested SARs in North American terrestrial tetrapods through the Cretaceous–Paleogene (K/Pg) mass extinction (Campanian–Ypresian). We show that SARs vary substantially through time and among groups. In the pre-extinction interval (Maastrichtian), unusually shallow SAR slopes (indicating low beta diversity or provinciality) drive low total regional diversity in dinosaurs, mammals, and other tetrapods. In the immediate postextinction interval (Danian), the explosive diversification of mammals drove high regional diversity via a large increase in SAR slope (indicating higher beta diversity or provinciality), and only a limited increase in SAR intercept. This contradicts the expectation that postextinction biotas should be regionally homogenized by the spread of disaster taxa and impoverished by diversity loss. This early postextinction increase in SAR slope was followed in the Thanetian–Selandian ( ∌ 4.4. myr later) by increases in the intercept, indicating that diversity dynamics at local and regional scales did not change in synchrony.
GPT-4o mini: Non-social science research article
Allosteric mechanism in the distinctive coupling of G q and G s to the parathyroid hormone type 1 receptor
Xuan Zhang, Ji Young Lee, Jonathan Pacheco, Ieva Sutkeviciute, Anju Krishnan Anitha, Heng Liu, Stephanie Singh, Carlos Ventura, Sofya Savransky, Ashok Khatri, Cheng Zhang, Ivet Bahar, Jean-Pierre Vilardaga
Full text
The mechanism determining the preferential stimulation of one heterotrimeric G protein signaling pathway over another by a ligand remains undetermined. By reporting the cryogenic electron microscopy (cryo-EM) structure of the parathyroid hormone (PTH) type 1 receptor (PTH1R) complexed with Gq and comparing its allosteric dynamics with that of PTH1R in complex with G s , we uncover a mechanism underlying such preferences. We show that an allosteric coupling between the ligand PTH and the C-terminal helix α5 of the Gα subunit controls the stability of the PTH1R complex with the specific G protein, G s or G q . Single-cell-level experiments further validate the G protein–selective effects of the PTH binding pose by demonstrating the differential, G protein–dependent residence times and affinity of this ligand at the PTH1R binding site. The findings deepen our understanding of the selective coupling of PTH1R to G s or G q and how it relates to the stability and kinetics of ligand binding. They explain the observed variability in the ligand-binding affinity of a GPCR when coupled to different G proteins.
GPT-4o mini: Non-social science research article
Molecular design principles for bipolar spindle organization by two opposing motors
Wei-Xiang Chew, François Nédélec, Thomas Surrey
Full text
During cell division in animal cells, a bipolar spindle assembles to segregate the chromosomes. Various motor proteins with different properties are essential for spindle self-organization. The minimal set of components required to organize dynamic microtubules into a bipolar network remains however unknown. Here, we use computer simulations to explore whether two types of microtubule-crosslinking motors with opposite directionality can organize dynamic microtubules into bipolar spindles in three-dimensional space around a local microtubule nucleation source. We find that two motors are indeed sufficient, provided their properties resemble the main human spindle motors kinesin-5 and dynein, revealing the core mechanism of spindle self-organization. It is based on the synergistic interplay of a slow plus-directed symmetric motor and a fast minus-directed asymmetric motor. A hypothetical symmetric minus-directed motor can also support spindle formation together with kinesin-5, but only in a limited and unphysiological parameter range. In agreement with its accessory role in human cells, a minus motor with human kinesin-14 properties does not assemble stable bipolar spindles together with kinesin-5. These results reveal fundamental principles for the self-organization of dynamic bipolar microtubule architectures and highlight how distinct molecular designs of mitotic motors are optimized for their task.
GPT-4o mini: Non-social science research article
Correction for Quach et al., Deep learning–driven bacterial cytological profiling to determine antimicrobial mechanisms in Mycobacterium tuberculosis
Full text
GPT-4o mini: Non-social science research article
ETV5 reduces androgen receptor expression and induces neural stem–like properties during neuroendocrine prostate cancer development
Jongeun Lee, Jiho Park, Yunjung Hur, Dahun Um, Hyung-Seok Choi, Joonyoung Park, Yewon Kim, Jeon-Soo Lee, Kyuha Choi, Eunjeong Kim, Young Bin Park, Jae-Mun Choi, Tae-Kyung Kim, Yoontae Lee
Full text
Neuroendocrine prostate cancer (NEPC), an aggressive subtype induced by hormone therapy, lacks effective treatments. This study explored the role of E26 transformation-specific variant 5 (ETV5) in NEPC development. Analysis of multiple prostate cancer datasets revealed that NEPC is characterized by significantly elevated ETV5 expression compared to other subtypes. ETV5 expression increased progressively under hormone therapy through epigenetic modifications. ETV5 induced neural stem–like features in prostate cancer cells and facilitated their differentiation into NEPC under hormone treatment conditions, both in vitro and in vivo. Our molecular mechanistic study identified PBX3 and TLL1 as target genes of ETV5 that contribute to ETV5 overexpression–induced castration resistance and stemness. Notably, obeticholic acid, identified as an ETV5 inhibitor in this study, exhibited promising efficacy in suppressing NEPC development. This study highlights ETV5 as a key transcription factor that facilitates NEPC development and underscores its potential as a therapeutic target for this aggressive cancer subtype.
GPT-4o mini: Non-social science research article
Magnetic suppression of quantum tunneling: Insights from Fefferman, Shapiro, and Weinstein
Percy A. Deift
Full text
GPT-4o mini: Non-social science research article
Adaptive ATP-induced molecular condensation in membranized protocells
Vincent Mukwaya, Xiaolei Yu, Shuo Yang, Stephen Mann, Hongjing Dou
Full text
Liquid–liquid phase separation (LLPS) has been achieved in various cytomimetic (protocell) models, but controlling molecular condensation using noninert crowders to systematically alter protocell function remains challenging. Intracellular ATP levels influence protein–protein interactions, and dysregulation of ATP can alter cellular crowding dynamics, thereby disrupting the normal formation or dissolution of condensates. Here, we develop a membranized protocell model capable of endogenous LLPS and liquid–gel-like phase separation through precise manipulation of intermolecular interactions within semipermeable polysaccharide-based microcapsules (polysaccharidosomes, P-somes), prepared using microtemplate-guided assembly. We demonstrate that intraprotocellular diffusion-mediated LLPS can be extended into the liquid–gel-like domain by the uptake of the biologically active crowder ATP, resulting in a range of modalities dependent on the fine-tuning of molecular condensation. Endogenous enzyme activity in these crowded polysaccharidosomes is enhanced compared to free enzymes in solution, though this enhancement diminishes at higher levels of intraprotocellular condensation. Additionally, increased molecular crowding inhibits intraprotocell DNA strand displacement reactions. Our findings introduce an expedient and optimized approach to the batch construction of membranized protocell models with controllable molecular crowding and functional diversity. Our mix–incubate–wash protocol for inducing endogenous LLPS in membranized protocells offers potential applications in microreactor technology, environmental sensing, and the delivery and sustained release of therapeutics.
GPT-4o mini: Non-social science research article
Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes
Michael C. Sierant, Sheng Chih Jin, Kaya Bilguvar, Sarah U. Morton, Weilai Dong, Wei Jiang, Ziyu Lu, Boyang Li, Francesc LĂłpez-GirĂĄldez, Irina Tikhonova, Xue Zeng, Qiongshi Lu, Jungmin Choi, Junhui Zhang, Carol Nelson-Williams, James R. Knight, Hongyu Zhao, Junyue Cao, Shrikant Mane, Stanley C. Sedore, Peter J. Gruber, Monkol Lek, Elizabeth Goldmuntz, John Deanfield, Alessandro Giardini, Seema Mital, Mark Russell, J. William Gaynor, Eileen King, Michael Wagner, Deepak Srivastava, Yufeng Shen, Daniel Bernstein, George A. Porter, Jane W. Newburger, Jonathan G. Seidman, Amy E. Roberts, Mark Yandell, H. Joseph Yost, Martin Tristani-Firouzi, Richard Kim, Wendy K. Chung, Bruce D. Gelb, Christine E. Seidman, Martina Brueckner, Richard P. Lifton
Full text
Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent–offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to 4 subtypes. Seven genes were only associated with isolated CHD, while 37 were associated with 1 or more extracardiac abnormalities. Genes selectively expressed in the cardiomyocyte lineage were associated with isolated CHD, while those widely expressed in the brain were also associated with neurodevelopmental delay (NDD). Missense variants introducing or removing cysteines in epidermal growth factor (EGF)-like domains of NOTCH1 were enriched in tetralogy of Fallot and conotruncal defects, unlike the broader CHD spectrum seen with loss of function variants. Transmitted damaging missense variants in MYH6 were enriched in multiple CHD phenotypes and account for ~1% of all probands. Probands with characteristic mutations causing syndromic CHD were frequently not diagnosed clinically, often due to missing cardinal phenotypes. CHD genes that were positively or negatively associated with development of NDD suggest clinical value of genetic testing. These findings expand the understanding of CHD genetics and support the use of molecular diagnostics in CHD.
GPT-4o mini: Non-social science research article
Order–disorder transition in multidirectional crowds
Karol A. Bacik, Grzegorz Sobota, Bogdan S. Bacik, Tim Rogers
Full text
One of the archetypal examples of active flows is a busy concourse crossed by people moving in different directions according to their personal destinations. When the crowd is isotropic—comprising individuals moving in all different directions—the collective motion is disordered. In contrast, if it is possible to identify two dominant directions of motion, for example in a corridor, the crowd spontaneously organizes into contraflowing lanes or stripes. In this article, we characterize the physics of the transition between these two distinct phases by using a synergy of theoretical analysis, numerical simulations, and stylized experiments. We develop a hydrodynamic theory for collisional flows of heterogeneous populations, and we analyze the stability of the disordered configuration. We identify an order–disorder transition occurring as population heterogeneity exceeds a theoretical threshold determined by the collision avoidance maneuvers of the crowd. Our prediction for the onset of pedestrian ordering is consistent with results of agent-based simulations and controlled experiments with human crowds.
GPT-4o mini: Non-social science research article
Observation of odd-parity superconductivity in UTe 2
Zixuan Li, Camilla M. Moir, Nathan J. McKee, Eric Lee-Wong, Ryan E. Baumbach, M. Brian Maple, Ying Liu
Full text
Symmetry properties of the order parameter are among the most fundamental characteristics of a superconductor. UTe 2 , which was found to feature an exceedingly large upper critical field and striking reentrant behavior at low temperatures, is widely believed to possess a spin-triplet pairing symmetry. However, unambiguous evidence for such a pairing symmetry is still lacking, especially at zero and low magnetic fields. The presence of an inversion crystalline symmetry in UTe 2 requires that, if it is indeed a spin-triplet superconductor, the order parameter must be of odd parity. We report here phase-sensitive measurements of the symmetry of the orbital part of the order parameter using the Josephson effect. The selection rule in the orientation dependence of the Josephson coupling between In, an s -wave superconductor, and UTe 2 suggests strongly that UTe 2 possesses the odd-parity pairing state of B 1 u symmetry near zero magnetic field, making it a spin-triplet superconductor. We also report the apparent formation of Andreev surface bound states on the (1−10) surface of UTe 2 .
GPT-4o mini: Non-social science research article
De novo discovery of a molecular glue–like macrocyclic peptide that induces MCL1 homodimerization
Fengwei Li, Mengmeng Zhang, Chao Liu, Jie Cheng, Yawen Yang, Xiangda Peng, Zhifeng Li, Wenfeng Cai, Haipeng Yu, Junjie Wu, Yuyu Guo, Hongkun Geng, Yun Fa, Youming Zhang, Dalei Wu, Yizhen Yin
Full text
Macrocyclic peptides have emerged as promising drug candidates, filling the gap between small molecules and large biomolecules in drug discovery. The antiapoptotic protein myeloid cell leukemia 1 (MCL1) is crucial for numerous cancers, yet it presents challenges for selective targeting by traditional inhibitors. In this study, we identified a macrocyclic peptide, 5L1, that strongly binds to MCL1, with a dissociation constant ( K D ) of 7.1 nM. This peptide shows the potential to specifically inhibit the function of MCL1, and demonstrates effective antitumor activity against several blood tumor cell lines with the half maximal inhibitory concentration (IC 50 ) values for cell-penetrating peptide-conjugated 5L1 in the range of 0.6 to 3 ÎŒM. Structural analysis revealed that it functions similarly to molecular glue, capable of binding to two MCL1 molecules simultaneously and inducing their homodimerization. This unique mechanism of action distinguishes it from traditional small-molecule MCL1 inhibitors, underscoring the potential of macrocyclic peptides functioning as molecular glues. Moreover, it inspires the development of highly selective inhibitors targeting MCL1 and other related targets with this glue-like mechanism.
GPT-4o mini: Non-social science research article
Prediction of phase-separation propensities of disordered proteins from sequence
Sören von BĂŒlow, Giulio Tesei, Fatima Kamal Zaidi, Tanja Mittag, Kresten Lindorff-Larsen
Full text
Phase separation is one possible mechanism governing the selective cellular enrichment of biomolecular constituents for processes such as transcriptional activation, mRNA regulation, and immune signaling. Phase separation is mediated by multivalent interactions of macromolecules including intrinsically disordered proteins and regions (IDRs). Despite considerable advances in experiments, theory, and simulations, the prediction of the thermodynamics of IDR phase behavior remains challenging. We combined coarse-grained molecular dynamics simulations and active learning to develop a fast and accurate machine learning model to predict the free energy and saturation concentration for phase separation directly from sequence. We validate the model using computational and previously measured experimental data, as well as new experimental data for six proteins. We apply our model to all 27,663 IDRs of chain length up to 800 residues in the human proteome and find that 1,420 of these (5%) are predicted to undergo homotypic phase separation with transfer free energies < −2 k B T . We use our model to understand the relationship between single-chain compaction and phase separation and find that changes from charge- to hydrophobicity-mediated interactions can break the symmetry between intra- and intermolecular interactions. We also provide proof of principle for how the model can be used in force field refinement. Our work refines and quantifies the established rules governing the connection between sequence features and phase-separation propensities, and our prediction models will be useful for interpreting and designing cellular experiments on the role of phase separation, and for the design of IDRs with specific phase-separation propensities.
GPT-4o mini: Non-social science research article
Neural basis for individual differences in the attention-enhancing effects of methylphenidate
Peter Manza, Dardo Tomasi, ĆžĂŒkrĂŒ BarÄ±ĆŸ Demiral, Ehsan Shokri-Kojori, Christina Lildharrie, Esther Lin, Gene-Jack Wang, Nora D. Volkow
Full text
Stimulant drugs that boost dopamine, like methylphenidate (MP), enhance attention and are effective treatments for attention-deficit hyperactivity disorder (ADHD). Yet there is large individual variation in attentional capacity and response to MP. It is unclear whether this variation is driven by individual differences in relative density of dopamine receptor subtypes, magnitude of dopamine increases induced by MP, or both. Here, we extensively characterized the brain dopamine system with positron emission tomography (PET) imaging (including striatal dopamine D1 and D2/3 receptor availability and MP-induced dopamine increases) and measured attention task-evoked fMRI brain activity in two separate sessions (placebo and 60 mg oral MP; single-blind, counterbalanced) in 37 healthy adults. A network of lateral frontoparietal and visual cortices was sensitive to increasing attentional (and working memory) load, whose activity positively correlated with performance across individuals (partial r = 0.474, P = 0.008; controlling for age). MP-induced change in activity within this network correlated with MP-induced change in performance (partial r = 0.686, P < 0.001). The ratio of D1-to-D2/3 receptors in dorsomedial caudate positively correlated with baseline attentional network activity and negatively correlated with MP-induced changes in activity (all pFWE < 0.02). MP-induced changes in attentional load network activity mediated the association between D1-to-D2/3 ratio and MP-induced improvements in performance (mediation estimate = 23.20 [95%CI: −153.67 −81.79], P = 0.004). MP attention-boosting effects were not linked to the magnitude of striatal dopamine increases, but rather showed dependence on an individual’s baseline receptor density. Individuals with lower D1-to-D2/3 ratios tended to have lower frontoparietal activity during sustained attention and experienced greater improvement in brain function and task performance with MP.
GPT-4o mini: Non-social science research article
Global phase diagram of D-wave superconductivity in the square-lattice t-J model
Feng Chen, F. D. M. Haldane, D. N. Sheng
Full text
The Hubbard and closely related t-J models are exciting platforms for unconventional superconductivity (SC). Through state-of-the-art density matrix renormalization group calculations using the grand canonical ensemble, we address open issues regarding the ground-state phase diagram of the extended t-J model on a square lattice in the parameter regime relevant to cuprate superconductors. On large 8-leg cylinders, we demonstrate that the pure t-J model with only nearest-neighbor hoppings and superexchange interactions, for a wide range of doping ( ÎŽ = 0.1 to 0.2 ), hosts robust d-wave superconductivity possibly coexisting with weak unidirectional pair density wave. Furthermore, a small next nearest neighbor hopping t 2 suppresses pair and charge density waves, resulting in a uniform d-wave SC phase in both electron- and hole-doped cuprate model systems. Our work validates the t-J model as a proper minimum model for the emergence of superconductivity in cuprate superconductors.
GPT-4o mini: Non-social science research article
Isolated steady solutions of the 3D Euler equations
Alberto Enciso, Willi Kepplinger, Daniel Peralta-Salas
Full text
We show that there exist closed three-dimensional Riemannian manifolds where the incompressible Euler equations exhibit smooth steady solutions that are isolated in the C 1 -topology. The proof of this fact combines ideas from dynamical systems, which appear naturally because these isolated states have strongly chaotic dynamics, with techniques from spectral geometry and contact topology, which can be effectively used to analyze the steady Euler equations on carefully chosen Riemannian manifolds. Interestingly, much of this strategy carries over to the Euler equations in Euclidean space, leading to the weaker result that there exist analytic steady solutions on T 3 such that the only analytic steady Euler flows in a C 1 -neighborhood must belong to a certain linear space of dimension six. For comparison, note that in any C k -neighborhood of a shear flow, there are infinitely many linearly independent analytic shears.
GPT-4o mini: Non-social science research article
The Mediator subunit OsMED23 associates with the histone demethylase OsJMJ703 and the transcription factor OsWOX3A to control grain size and yield in rice
Luojiang Huang, Na Fang, Limin Zhang, Ran Xu, Baolan Zhang, Penggen Duan, Guansong Li, Yuehua Luo, Yunhai Li
Full text
Seed size is one of the important yield traits, and size control is also a fundamental developmental question. The knowledge about the genetic and molecular mechanisms that govern seed size is crucial for improving crop yield. Here, we report that the Mediator subunit OsMED23 associates with the histone demethylase OsJMJ703 and the transcription factor OsWOX3A to control grain size and weight in rice. Loss of function of OsMED23 or OsJMJ703 causes narrow and light grains, while overexpression of OsMED23 or OsJMJ703 results in large and heavy grains. OsMED23 physically interacts with OsJMJ703 and the transcription factor OsWOX3A. OsMED23, OsJMJ703, and OsWOX3A associate with the common promoter regions of two key grain size genes GW2 and OsLAC and repress their transcription by influencing H3K4me3 levels. Field trials demonstrate that overexpression of OsMED23 or OsJMJ703 can significantly increase grain yield. Therefore, our findings identify a mechanism by which the transcriptional repressor complex OsJMJ703-OsMED23-OsWOX3A determines grain size and weight by regulating gene expression and influencing H3K4me3 levels in rice, suggesting that this pathway has a great potential for improving grain yield in key crops.
GPT-4o mini: Non-social science research article
Control of circadian muscle glucose metabolism through the BMAL1–HIF axis in obesity
Claire A. Chaikin, Abhishek V. Thakkar, Adam W. T. Steffeck, Eric M. Pfrender, Kaitlyn Hung, Pei Zhu, Nathan J. Waldeck, Rino Nozawa, Weimin Song, Christopher R. Futtner, Mattia Quattrocelli, Joseph Bass, Issam Ben-Sahra, Clara B. Peek
Full text
Disruptions of circadian rhythms are widespread in modern society and lead to accelerated and worsened symptoms of metabolic syndrome. In healthy mice, the circadian clock factor BMAL1 is required for skeletal muscle function and metabolism. However, the importance of muscle BMAL1 in the development of metabolic diseases, such as diet-induced obesity (DIO), remains unclear. Here, we demonstrate that skeletal muscle–specific BMAL1-deficient mice exhibit worsened glucose tolerance upon high-fat diet feeding, despite no evidence of increased weight gain. Metabolite profiling from Bmal1 -deficient muscles revealed impaired glucose utilization specifically at early steps in glycolysis that dictate the switch between anabolic and catabolic glucose fate. We provide evidence that this is due to abnormal control of the nutrient stress–responsive hypoxia-inducible factor (HIF) pathway. Genetic HIF1α stabilization in muscle Bmal1 -deficient mice restores glucose tolerance and expression of 217/736 dysregulated genes during DIO, including glycolytic enzymes. Together, these data indicate that during DIO, skeletal muscle BMAL1 is an important regulator of HIF-driven glycolysis and metabolic flexibility, which influences the development of high-fat-diet-induced glucose intolerance.
GPT-4o mini: Non-social science research article
Matrix degradation enhances stress relaxation, regulating cell adhesion and spreading
Badri Narayanan Narasimhan, Stephanie I. Fraley
Full text
In native extracellular matrices (ECM), cells utilize matrix metalloproteinases (MMPs) to degrade and remodel their microenvironment. Accordingly, synthetic matrices have been engineered to permit MMP-mediated cleavage, facilitating cell spreading, migration, and interactions. However, the interplay between matrix degradability and mechanical properties remains underexplored. We hypothesized that MMP activity induces immediate mechanical alterations in the ECM, which are subsequently detected by cells. We observed that both fibrillar collagen and synthetic degradable matrices exhibit enhanced stress relaxation following MMP exposure. Cells responded to these variations in relaxation by modulating their spreading and focal adhesions. Furthermore, we demonstrated that stress relaxation and cell spreading can be precisely controlled through the rational design of matrix degradability. These findings establish a fundamental link between matrix degradability and stress relaxation, with potential implications for a broad spectrum of biological applications.
GPT-4o mini: Non-social science research article
Actuating superparamagnetic nanoparticle monolayers
Edward P. Esposito, Hector Manuel Lopez Rios, Monica Olvera de la Cruz, Heinrich M. Jaeger
Full text
Magnetically responsive, mechanically flexible microstructures are desirable for applications ranging from smart sensors to remote-controlled actuation for surgery or robotics. Embedding magnetic nanoparticles into a thin matrix of elastic material enables high flexibility while exploiting the magnetic response of the individual particles. However, in the ultrathin limit of such nanocomposite materials, the particles become too small to sustain a permanent dipole moment. This implies that now large magnetic field gradients are required for actuation, which are difficult to achieve with externally applied fields. Here, we demonstrate through experiment and simulation that monolayer sheets of close-packed paramagnetic nanoparticles in a uniform applied field can generate large local field gradients through particle interactions. As a result, a strong collective magnetization is obtained that leads to large deflections of freestanding sheets already in moderate applied fields. Exploiting the vector nature of the applied field, we furthermore find that it is possible to induce more complex curvature and twist the sheets. Finally, we show that paramagnetic nanoparticle monolayers applied as coatings can generate sufficient force to deflect strips of nonmagnetic material that is several orders of magnitude thicker.
GPT-4o mini: Non-social science research article
The PVD neuron has male-specific structure and mating function in Caenorhabditis elegans
Yael Iosilevskii, David H. Hall, Menachem Katz, Benjamin Podbilewicz
Full text
Neurons display unique shapes and establish intricate networks, which may differ between sexes. In complex organisms, studying sex differences in structure and function of individual neurons is difficult. The nematode Caenorhabditis elegans hermaphrodites and males present an exceptional model for studying neuronal morphogenesis in a simple, sexually dimorphic system. We focus on the polymodal sensory bilateral neuron pair PVD, which forms a complex but stereotypic dendritic tree composed of multiple subunits that resemble candelabra. PVD is well studied in hermaphrodites, but not in males. We show here that during larval development, male PVD extends a similar architecture to the hermaphrodite utilizing the sexually shared Menorin patterning mechanism. In early adulthood, however, male PVD develops a unique extension into the copulatory tail structure. Alongside established tail ray neurons RnA and RnB, we show PVD is a third, previously unrecognized, neuron within the tail rays. Unlike RnA and RnB, PVD extends anterogradely, branches and turns within the ray hypodermis, and is nonciliated. This PVD sexually dimorphic arborization is absent in mutant backgrounds which perturb the Menorin guidance complex. SAX-7/L1CAM, a hypodermal component of this complex, shows a male-specific expression pattern which precedes PVD extension, and its presence allows PVD to enter the tail rays. Further, our results reveal that genetically altered arborization or ablation of the PVD results in male mating behavioral defects, particularly as males turn around the hermaphrodite. These results uncover an adult-stage sexual dimorphism of dendritic branching and a function for PVD in male sexual behavior.
GPT-4o mini: Non-social science research article
Cytoplasmic Mg 2+ supersedes carbon source preference to dictate Salmonella metabolism
Nick D. Pokorzynski, Katarina A. Jones, Shawn R. Campagna, Eduardo A. Groisman
Full text
Glucose is the preferred carbon source of most studied microorganisms. However, we now report that glucose loses preferred status when the intracellular pathogen Salmonella enterica serovar Typhimurium experiences cytoplasmic magnesium (Mg 2+ ) starvation. We establish that this infection-relevant stress drastically reduces synthesis of cyclic adenosine monophosphate (cAMP), the allosteric activator of the cAMP receptor protein (CRP), master regulator of carbon utilization. The resulting reduction in cAMP concentration, which is independent of carbon source, decreases transcription of CRP-cAMP-activated carbon utilization genes, hinders carbon source uptake, and restricts metabolism, rendering wild-type bacteria phenotypically CRP − . A cAMP-independent allele of CRP overcame the transcriptional, uptake, and metabolic restrictions caused by cytoplasmic Mg 2+ starvation and significantly increased transcription of the glucose uptake gene when S. Typhimurium was inside murine macrophages. The reduced preference for glucose exhibited by S. Typhimurium inside macrophages reflects that transcription of the glucose uptake gene requires higher amounts of active CRP-cAMP than transcription of uptake genes for preferred carbon sources, such as gluconate and glycerol. By reducing CRP-cAMP activity, low cytoplasmic Mg 2+ alters carbon source preference, adjusting metabolism and growth.
GPT-4o mini: Non-social science research article
Correction for Ganguli et al., A culture-free biphasic approach for sensitive and rapid detection of pathogens in dried whole-blood matrix
Full text
GPT-4o mini: Non-social science research article
Nanosilica supplementation in tomato increases oviposition on stems and caterpillar mortality in the tomato pinworm
Kokou R. Fiaboe, Fathiya M. Khamis, Xavier Cheseto, Abdullahi A. Yusuf, Baldwyn Torto
Full text
Silicon-induced responses play a key role in plant defense against herbivory, though the underlying mechanisms remain underexplored. In this study, we examined how mesoporous silica nanoparticles (MSNs) affect tomato ( Solanum lycopersicum ) defense against an invasive and highly destructive lepidopteran herbivore, the tomato pinworm (TPW), Phthorimaea absoluta . In tomato plants supplemented with MSN, prior exposure to TPW oviposition shifted subsequent egg-laying from a preference for leaves to an even distribution between stems and leaves. This shift was not observed in nonsilicon-supplemented plants. Prolonged oviposition triggered pigmentation in the basal cells of type I glandular trichomes on the stems of silicon-supplemented plants. Chemical analysis by coupled gas chromatography-mass spectrometry revealed that the pigmented trichome was rich in soluble sugars (sucrose and l -arabinose) and waxes, dominated by the saturated hydrocarbon tetracosane. Bioassays with the crude extract of the pigmented trichome and a three-component sugar–wax blend replicated the oviposition and caterpillar response observed with the pigmented trichome, while individual components produced variable effects. While l -arabinose alone replicated the oviposition effects of the three-component sugar–wax blend, sucrose increased oviposition and caterpillar feeding and survival, while l -arabinose and tetracosane caused the highest caterpillar mortality. Additionally, these treatments altered caterpillar gut microbiota composition and influenced frass volatiles, which attracted the TPW natural enemies, Nesidiocoris tenuis (predator) and Neochrysocharis formosa (parasitoid). Our findings suggest that silicon supplementation increases tomato defense against TPW through oviposition-induced responses, which promotes recruitment of natural enemies.
GPT-4o mini: Non-social science research article
Age-dependent cytokine surge in blood precedes cancer diagnosis
Guangbo Chen, Azam Mohsin, Hong Zheng, Yael Rosenberg-Hasson, Cindy Padilla, Kavita Y. Sarin, Cornelia L. Dekker, Philip Grant, Holden T. Maecker, Ying Lu, David Furman, Shai Shen-Orr, Purvesh Khatri, Mark M. Davis
Full text
Aging is associated with increased variability and dysregulation of the immune system. We performed a system-level analysis of serum cytokines in a longitudinal cohort of 133 healthy individuals over 9 y. We found that cancer incidence is a major contributor to increased cytokine abundance variability. Circulating cytokines increase up to 4 y before a cancer diagnosis in subjects with age over 80 y. We also analyzed cytokine expression in 10 types of early-stage cancers from The Cancer Genome Atlas. We found that a similar set of cytokines is upregulated in tumor tissues, specifically after the age of 80 y. Similarly, cellular senescence activity and CDKN1A/p21 expression increase with age in cancer tissues. Finally, we demonstrated that the cytokine levels in serum can be used to predict cancers among subjects age at 80+ y. Our results suggest that latent senescent cancers contribute to age-related chronic inflammation.
GPT-4o mini: Non-social science research article
High-density CRISPRi screens reveal diverse routes to improved acclimation in cyanobacteria
Andrew Hren, Nicole Lollini, Dana L. Carper, Paul E. Abraham, Jeffrey C. Cameron, Jerome M. Fox, Carrie A. Eckert
Full text
Cyanobacteria are the oldest form of photosynthetic life on Earth and contribute to primary production in nearly every habitat, from permafrost to hot springs. Despite longstanding interest in the acclimation of these microbes, it remains poorly understood and challenging to rewire. This study uses a high-density, genome-wide CRISPR interference screen to examine the influence of gene-specific transcriptional variation on the growth of Synechococcus sp. PCC 7002 under environmental extremes. Surprisingly, many partial knockdowns enhanced fitness under cold monochromatic conditions. Transcriptional repression of genes for core subunits of the NDH-1 complex, which are important for photosynthesis and carbon uptake, improved growth rates under both red and blue light but at distinct, color-specific optima. Most genes with fitness-improving knockdowns were distinct to each light color, and dual-target transcriptional repression produced nonadditive effects. Findings reveal diverse routes to improved acclimation in cyanobacteria (e.g., attenuation of genes involved in CO 2 uptake, light harvesting, translation, and purine metabolism) and provide an approach for using gradients in sgRNA activity to pinpoint biochemically influential transcriptional changes in cells.
GPT-4o mini: Non-social science research article
Decoding in-cell respiratory enzyme dynamics by label-free in situ electrochemistry
Yoshihide Tokunou, Tomohiko Yamazaki, Takashi Fujikawa, Akihiro Okamoto
Full text
Deciphering metabolic enzyme catalysis in living cells remains a formidable challenge due to the limitations of in vivo assays, which focus on enzymes isolated from respiration. This study introduces an innovative whole-cell electrochemical assay to reveal the Michaelis–Menten landscape of respiratory enzymes amid complex molecular interactions. We controlled the microbial current generation’s rate-limiting step, extracting in vivo kinetic parameters ( K m , K i , and k cat ) for the periplasmic nitrite (NrfA) and fumarate (FccA) reductases. Notably, while NrfA kinetics mirrored those of its purified form, FccA exhibited unique kinetic behavior. Further exploration using a mutant strain lacking CymA, a periplasmic hub protein, revealed its crucial role in modulating FccA’s kinetics, challenging the prevailing view that molecular crowding is the main cause of discrepancies between in vivo and in vitro enzyme kinetics. This platform offers a groundbreaking approach to studying cellular respiratory enzymatic kinetics, paving the way for future research in bioenergetics and medicine.
GPT-4o mini: Non-social science research article
Accelerated peptide bond formation at air–water interfaces
Deming Xia, Fanqi Zeng, Wanting Chen, Hui Zhao, Hong-bin Xie, Jingwen Chen, Joseph S. Francisco
Full text
Peptides and proteins, essential components of living organisms, are composed of amino acids linked by peptide bonds. However, the mechanism of peptide bond formation during the prebiotic era remains unclear. In this study, advanced Born–Oppenheimer molecular dynamics (BOMD) simulations were used to investigate the mechanisms and kinetics of peptide bond formation at air–water interfaces using diglycine, the simplest dipeptide, as a model molecule. The results show that peptide bonds can be rapidly formed via a unique isomerization-then-OH − -elimination pathway. In this mechanism, the diglycine initially isomerizes into its acidic form at the air–water interface, followed by a reaction that releases an OH − anion rather than the previously hypothesized H 2 O. The free-energy barriers for the interfacial pathway with the assistance of an interfacial electric field are much lower than those in the gas phase by >25 kcal/mol. Further calculations suggest that this mechanism can be extended to the formation of some larger peptides, such as tetraglycine. This pathway offers insights into the origin of life and could inform the development of methods for peptide synthesis.
GPT-4o mini: Non-social science research article
In This Issue
Full text
GPT-4o mini: Non-social science research article
Rolling vesicles: From confined rotational flows to surface-enabled motion
Paula Magrinya, Pablo Palacios-Alonso, Pablo Llombart, Rafael Delgado-Buscalioni, Alfredo Alexander-Katz, Laura R. Arriaga, Juan L. Aragones
Full text
Friction forces are essential for cell movement, yet they also trigger numerous active cellular responses, complicating their measurement in vivo. Here, we introduce a synthetic model designed to measure friction forces between biomimetic membranes and substrates. The model consists of a vesicle with precisely controlled properties, fabricated via microfluidics, encapsulating a single ferromagnetic particle that is magnetically driven to rotate. The rotation of the particle generates a confined rotational flow, setting the vesicle membrane into motion. By adjusting the magnetic field frequency and vesicle size, the rotation frequency of the vesicle can be finely controlled, resulting in a rolling vesicle that functions as an effective tribological tool across a wide frequency range. At low frequencies, molecular contact between the membrane and substrate dominates frictional interactions, which enables determination of the contact friction coefficient. At higher frequencies, lubrication becomes predominant, causing the vesicles to slip rather than roll. Adjusting membrane fluidity and incorporating specific ligand–receptor interactions within this model will enable detailed studies of frictional forces in more complex biomimetic systems, providing key insights into the mechanisms of cell movement and mechanotransduction.
GPT-4o mini: Non-social science research article
Structure of ATP synthase from an early photosynthetic bacterium Chloroflexus aurantiacus
Xin Zhang, Jingyi Wu, Zhenzhen Min, Jiamao Wang, Xin Hong, Xinkai Pei, Zihe Rao, Xiaoling Xu
Full text
F-type ATP synthase (F 1 F O ) catalyzes proton motive force-driven ATP synthesis in mitochondria, chloroplasts, and bacteria. Different from the mitochondrial and bacterial enzymes, F 1 F O from photosynthetic organisms have evolved diverse structural and mechanistic details to adapt to the light-dependent reactions. Although complete structure of chloroplast F 1 F O has been reported, no high-resolution structure of an F 1 F O from photosynthetic bacteria has been available. Here, we report cryo-EM structures of an intact and functionally competent F 1 F O from Chloroflexus aurantiacus ( Ca F 1 F O ), a filamentous anoxygenic phototrophic bacterium from the earliest branch of photosynthetic organisms. The structures of Ca F 1 F O in its ADP-free and ADP-bound forms for three rotational states reveal a previously unrecognized architecture of ATP synthases. A pair of peripheral stalks connect to the Ca F 1 head through a dimer of ή-subunits, and associate with two membrane-embedded a-subunits that are asymmetrically positioned outside and clamp Ca F O ’s c 10 -ring. The two a-subunits constitute two proton inlets on the periplasmic side and two proton outlets on the cytoplasmic side, endowing Ca F 1 F O with unique proton translocation pathways that allow more protons being translocated relative to single a-subunit F 1 F O . Our findings deepen understanding of the architecture and proton translocation mechanisms of F 1 F O synthases and suggest innovative strategies for modulating their activities by altering the number of a-subunit.
GPT-4o mini: Non-social science research article
The architecture of sponge choanocyte chambers is well adapted to mechanical pumping functions
Takumi Ogawa, Shuji Koyama, Toshihiro Omori, Kenji Kikuchi, HĂ©lĂšne de Maleprade, Raymond E. Goldstein, Takuji Ishikawa
Full text
Sponges, the basalmost members of the animal kingdom, exhibit a range of complex architectures in which microfluidic channels connect multitudes of spherical chambers lined with choanocytes, flagellated filter-feeding cells. Choanocyte chambers can possess scores or even hundreds of such cells, which drive complex flows entering through porous walls and exiting into the sponge channels. One of the mysteries of the choanocyte chamber is its spherical shape, as it seems inappropriate for inducing directional transport since many choanocyte flagella beat in opposition to such a flow. Here, we combine direct imaging of choanocyte chambers in living sponges with computational studies of many-flagella models to understand the connection between chamber architecture and directional flow. We find that those flagella that beat against the flow play a key role in raising the pressure inside the choanocyte chamber, with the result that the flow rate and mechanical pumping efficiency reach a maximum at a small outlet opening angle. Comparison between experimental observations and the results of numerical simulations reveal that the chamber diameter, flagellar wave number, and the outlet opening angle of the freshwater sponge Ephydatia muelleri , as well as several other species, are related in a manner that maximizes the mechanical pumping functions. These results indicate the subtle balances at play during morphogenesis of choanocyte chambers, and give insights into the physiology and body design of sponges.
GPT-4o mini: Non-social science research article
Using net-zero carbon debt to track climate overshoot responsibility
Setu Pelz, Gaurav Ganti, Robin Lamboll, Luke Grant, Chris Smith, Shonali Pachauri, Joeri Rogelj, Keywan Riahi, Wim Thiery, Matthew J. Gidden
Full text
Current emissions trends will likely deplete a 1.5 °C consistent carbon budget around the year 2030, resulting in at least a temporary exceedance, or overshoot. To clarify responsibilities for this budget exceedance, we consider “net-zero carbon debt,” a forward-looking measure of the extent to which a party is expected to breach its “fair share” of the remaining budget by the time it achieves net-zero carbon emissions. We apply this measure to all vetted mitigation scenarios assessed in the Intergovernmental Panel on Climate Change’s Sixth Assessment Report and two scenarios that model current policies and pledges, using an illustrative equal per capita allocation of a remaining 1.5 °C carbon budget starting in 1990. The resulting regional carbon debt estimates inform i) the scale and pace of regional carbon drawdown obligations necessary to address budget exceedance and ii) relative regional responsibilities for increased lifetime exposure to extreme heatwaves across age cohorts due to budget exceedance. Our work strengthens intergenerational equity considerations within an international climate equity discourse and informs the implementation of effort-sharing mechanisms that persist beyond the exhaustion of a rapidly dwindling remaining carbon budget.
GPT-4o mini: Non-social science research article
Large-scale combination screens reveal small-molecule sensitization of antibiotic-resistant gram-negative ESKAPE pathogens
Megan W. Tse, Meilin Zhu, Benjamin Peters, Efrat Hamami, Julie Chen, Kathleen P. Davis, Samuel Nitz, Juliane Weller, Thulasi Warrier, Diana K. Hunt, Yoelkys Morales, Tomohiko Kawate, Jeffrey L. Gaulin, Jon H. Come, Juan Hernandez-Bird, Wenwen Huo, Isabelle Neisewander, Xiao Yu, Jose A. Aceves-Salvador, Laura L. Kiessling, Deborah T. Hung, Joan Mecsas, Bree B. Aldridge, Ralph R. Isberg, Paul C. Blainey
Full text
Antibiotic resistance, especially in multidrug-resistant ESKAPE pathogens, remains a worldwide problem. Combination antimicrobial therapies may be an important strategy to overcome resistance and broaden the spectrum of existing antibiotics. However, this strategy is limited by the ability to efficiently screen large combinatorial chemical spaces. Here, we deployed a high-throughput combinatorial screening platform, DropArray, to evaluate the interactions of over 30,000 compounds with up to 22 antibiotics and 6 strains of gram-negative ESKAPE pathogens, totaling to over 1.3 million unique strain-antibiotic-compound combinations. In this dataset, compounds more frequently exhibited synergy with known antibiotics than single-agent activity. We identified a compound, P2-56, and developed a more potent analog, P2-56-3, which potentiated rifampin (RIF) against antibiotic-resistant strains of Acinetobacter baumannii and Klebsiella pneumoniae . Using phenotypic assays, we showed P2-56-3 disrupts the outer membrane of A. baumannii . To identify pathways involved in the mechanism of synergy between P2-56-3 and RIF, we performed genetic screens in A. baumannii . CRISPRi-induced partial depletion of lipooligosaccharide transport genes ( lptA - D , lptFG ) resulted in hypersensitivity to P2-56-3/RIF treatment, demonstrating the genetic dependency of P2-56-3 activity and RIF sensitization on lpt genes in A. baumannii. Consistent with outer membrane homeostasis being an important determinant of P2-56-3/RIF tolerance, knockout of maintenance of lipid asymmetry complex genes and overexpression of certain resistance-nodulation-division efflux pumps—a phenotype associated with multidrug-resistance—resulted in hypersensitivity to P2-56-3. These findings demonstrate the immense scale of phenotypic antibiotic combination screens using DropArray and the potential for such approaches to discover new small molecule synergies against multidrug-resistant ESKAPE strains.
GPT-4o mini: Non-social science research article
The FBXW7–KMT2 axis in cancer-associated fibroblasts controls tumor growth via an epigenetic-paracrine mechanism
Lu Yin, Jiagui Zhang, Zhipeng Zhu, Xiaojuan Peng, Huiyin Lan, Alex Ayoub, Mingjia Tan, Bo Zhou, Yaohui He, Siyuan Wang, Yan Lu, Wen Liu, Xiufang Xiong, Jing Huang, Yali Dou, Fengbiao Mao, Yi Sun
Full text
F-box and WD repeat domain-containing 7 (FBXW7) is a tumor suppressor that targets various oncoproteins for degradation, but its role in modulating cancer-associated fibroblasts (CAFs) in the tumor microenvironment remains elusive. Here, we report that FBXW7 expression is gradually downregulated in CAFs during the progression of human pancreatic and lung cancers. Mechanically, FBXW7 inhibits histone lysine methyltransferase 2 (KMT2) methyltransferase activity via retinoblastoma binding protein 5 (RbBP5) binding, whereas FBXW7 depletion abrogates the binding to activate KMT2, leading to increased H3K4 methylations and global upregulation of gene expression. Activation of the interleukin-17 (IL-17) signaling pathway triggers the secretion of cytokines and chemokines to promote migration, invasion, and sphere formation of lung cancer cells. Coinjection of Fbxw7-depleted mouse embryonic fibroblasts with cancer cells enhances in vivo tumor growth, demonstrating a paracrine effect. Hypoxia downregulates CAF FBXW7 via ETS proto-oncogene 1 (ETS1) to increase H3K4 methylation, whereas conditioned media from hypoxia-exposed CAFs promotes migration and invasion of pancreatic cancer cells, highlighting FBXW7’s tumor-suppressing role through KMT2 inactivation.
GPT-4o mini: Non-social science research article
In situ cavitation bubble manometry reveals a lack of light-activated guard cell turgor modulation in bryophytes
Craig R. Brodersen, Tim J. Brodribb, Uri Hochberg, N. Michele Holbrook, Scott A. M. McAdam, Joseph Zailaa, Brett A. Huggett, Philippe Marmottant
Full text
Diversification of plant hydraulic architecture and stomatal function coincides with radical changes in the Earth’s atmosphere over the past 400 my. Due to shared stomatal anatomy with the earliest land plants, bryophyte stomatal behavior may provide insights into the evolution of stomatal function, but significant uncertainty remains due to technical limitations of measuring guard cell turgor pressure in situ. Here, we introduce a method for monitoring cell turgor pressure by nucleating microbubbles within the guard cells of intact plant tissue and then examining microbubble growth and dissolution dynamics. First, we show that maximum microbubble radius decreases with increasing pressure as the pressure of the surrounding fluid constrains its growth according to a modified version of the Epstein–Plesset equation. We then apply this method to monitor turgor pressure in dark- vs. light-acclimated guard cells across bryophyte taxa with stomata, where their role in gas-exchange remains ambiguous, and in vascular plants with well-documented light-dependent turgor modulation. Our findings show no light-activated change in turgor in bryophyte guard cells, with pressures not significantly different than neighboring epidermal cells. In contrast, vascular plants show distinct pressure modulation in response to light that drives reversible changes in stomatal aperture. Complete guard cell turgor loss had no effect on bryophyte stomatal aperture but resulted in partial or complete closure in vascular plants. These results suggest that despite conserved stomatal morphology, the sampled bryophytes lack dynamic control over guard cell turgor that is critical for sustaining photosynthesis and inhibiting desiccation.
GPT-4o mini: Non-social science research article
An atlas of protein phosphorylation dynamics during interferon signaling
Idoia Busnadiego, Marie Lork, Sonja Fernbach, Samira Schiefer, Nikos Tsolakos, Benjamin G. Hale
Full text
Interferons (IFNs, types I-III) have pleiotropic functions in promoting antiviral and antitumor responses, as well as in modulating inflammation. Dissecting the signaling mechanisms elicited by different IFNs is therefore critical to understand their phenotypes. Here, we use mass spectrometry to investigate the early temporal dynamics of cellular protein phosphorylation in a human lung epithelial cell-line as it responds to stimulation with IFNα2, IFNÎČ, IFNω, IFNÎł, or IFNλ1, representing all IFN types. We report an atlas of over 700 common or unique phosphorylation events reprogrammed by these different IFNs, revealing both previously known and uncharacterized modifications. While the proteins differentially phosphorylated following IFN stimulation have diverse roles, there is an enrichment of factors involved in chromatin remodeling, transcription, and RNA splicing. Functional screening and mechanistic studies identify that several proteins modified in response to IFNs contribute to host antiviral responses, either directly or by supporting IFN-stimulated gene or protein production. Among these, phosphorylation of PLEKHG3 at serine-1081 creates a phospho-regulated binding motif for the docking of 14-3-3 proteins, and together these factors contribute to coordinating efficient IFN-stimulated gene expression independent of early Janus kinase/signal transducer and activator of transcription signaling. Our findings map the global phosphorylation landscapes regulated by IFN types I, II, and III, and provide a key resource to explore their functional consequences.
GPT-4o mini: Non-social science research article
Potassium-sensitive loss of muscle force in the setting of reduced inward rectifier K + current: Implications for Andersen–Tawil syndrome
Nathaniel Elia, Marbella Quiñonez, Fenfen Wu, Ekaterina Mokhonova, Marino DiFranco, Melissa J. Spencer, Stephen C. Cannon
Full text
Andersen–Tawil syndrome (ATS) is an ion channelopathy with variable penetrance for the triad of periodic paralysis, arrhythmia, and dysmorphia. Dominant-negative mutations of KCNJ2 encoding the Kir2.1 potassium channel subunit are found in 60% of ATS families. As with most channelopathies, episodic attacks in ATS are frequently triggered by environmental stresses: exercise for periodic paralysis or stress with adrenergic stimulation for arrhythmia. Fluctuations in K + , either low or high, are potent triggers for attacks of weakness in other variants of periodic paralysis (hypokalemic periodic paralysis or hyperkalemic periodic paralysis). For ATS, the [K + ] dependence is less clear; with reports describing weakness in high-K + or low-K + . Patient trials with controlled K + challenges are not possible, due to arrhythmias. We have developed two mouse models (genetic and pharmacologic) with reduced Kir currents, to address the question of K + -sensitive loss of force. These animal models and computational simulations both show K + -dependent weakness occurs only when Kir current is <30% of wildtype. As the Kir deficit becomes more severe, the phenotype shifts from high-K + -induced weakness to a combination where either high-K + or low-K + triggers weakness. A K + channel agonist, retigabine, protects muscle from K + -sensitive weakness in our mouse models of the skeletal muscle involvement in ATS.
GPT-4o mini: Non-social science research article
Bridging the human–AI knowledge gap through concept discovery and transfer in AlphaZero
Lisa Schut, Nenad TomaĆĄev, Thomas McGrath, Demis Hassabis, Ulrich Paquet, Been Kim
Full text
AI systems have attained superhuman performance across various domains. If the hidden knowledge encoded in these highly capable systems can be leveraged, human knowledge and performance can be advanced. Yet, this internal knowledge is difficult to extract. Due to the vast space of possible internal representations, searching for meaningful new conceptual knowledge can be like finding a needle in a haystack. Here, we introduce a method that extracts new chess concepts from AlphaZero, an AI system that mastered chess via self-play without human supervision. Our method excavates vectors that represent concepts from AlphaZero’s internal representations using convex optimization, and filters the concepts based on teachability (whether the concept is transferable to another AI agent) and novelty (whether the concept contains information not present in human chess games). These steps ensure that the discovered concepts are useful and meaningful. For the resulting set of concepts, prototypes (chess puzzle–solution pairs) are presented to experts for final validation. In a preliminary human study, four top chess grandmasters (all former or current world chess champions) were evaluated on their ability to solve concept prototype positions. All grandmasters showed improvement after the learning phase, suggesting that the concepts are at the frontier of human understanding. Despite the small scale, our result is a proof of concept demonstrating the possibility of leveraging knowledge from a highly capable AI system to advance the frontier of human knowledge; a development that could bear profound implications and shape how we interact with AI systems across many applications.
GPT-4o mini: Non-social science research article
Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing
Andrey Damianov, Chia-Ho Lin, Jian Zhang, James L. Manley, Douglas L. Black
Full text
Myelodysplastic syndromes and other cancers are often associated with mutations in the U2 snRNP protein SF3B1. Common SF3B1 mutations, including K700E, disrupt SF3B1 interaction with the protein SUGP1 and induce aberrant activation of alternative 3â€Č splice sites (ss), presumably resulting from aberrant U2/branch site (BS) recognition by the mutant spliceosome. Here, we apply a method of U2 IP-seq to profile BS binding across the transcriptome of K562 leukemia cells carrying the SF3B1 K700E mutation. For alternative 3â€Č ss activated by K700E, we identify their associated BSs and show that they are indeed shifted from the WT sites. Unexpectedly, we also identify thousands of additional changes in BS binding in the mutant cells that do not alter splicing. These new BSs are usually very close to the natural sites, occur upstream or downstream, and either exhibit stronger base-pairing potential with U2 snRNA or are adjacent to stronger polypyrimidine tracts than the WT sites. The widespread imprecision in BS recognition induced by K700E with limited changes in 3â€Č ss selection expands the physiological consequences of this oncogenic mutation.
GPT-4o mini: Non-social science research article
Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination
Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf, Gregory Strout, Xiangming Fang, Marco Colonna
Full text
We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the Trem2 gene in mice impairs remyelination. Here, we blocked TREM2 function acutely with an antibody during both the demyelination and remyelination phases of the CPZ model and analyzed the impact of the antibody treatment on myelination and gene expression in single cells. We found that blocking TREM2 depleted a distinct population of microglia with high expression of the transcription factor MAFB during remyelination. The loss of these MAFB-high microglia was linked to impaired generation of myelinating oligodendrocytes. Importantly, we identified MAFB + microglia in acute and acute-chronic brain lesions from individuals with multiple sclerosis (MS), but not in inactive lesions. We conclude that TREM2 is essential for maintaining a population of MAFB-high microglia that is associated with myelin repair. This finding has significant implications for understanding demyelinating diseases like MS and suggests that stimulating TREM2 could be a promising therapeutic approach for myelin repair.
GPT-4o mini: Non-social science research article
Bacteria on steroids
Natalia Mrnjavac, William F. Martin
Full text
GPT-4o mini: Non-social science research article
Active matter as the underpinning agency for extraordinary sensitivity of biological membranes to electric fields
Anand Mathew, Yashashree Kulkarni
Full text
Interaction of electric fields with biological cells is indispensable for many physiological processes. Thermal electrical noise in the cellular environment has long been considered as the minimum threshold for detection of electrical signals by cells. However, there is compelling experimental evidence that the minimum electric field sensed by certain cells and organisms is many orders of magnitude weaker than the thermal electrical noise limit estimated purely under equilibrium considerations. We resolve this discrepancy by proposing a nonequilibrium statistical mechanics model for active electromechanical membranes and hypothesize the role of activity in modulating the minimum electrical field that can be detected by a biological membrane. Active membranes contain proteins that use external energy sources to carry out specific functions and drive the membrane away from equilibrium. The central idea behind our model is that active mechanisms, attributed to different sources, endow the membrane with the ability to sense and respond to electric fields that are deemed undetectable based on equilibrium statistical mechanics. Our model for active membranes is capable of reproducing different experimental data available in the literature by varying the activity. Elucidating how active matter can modulate the sensitivity of cells to electric signals can open avenues for a deeper understanding of physiological and pathological processes.
GPT-4o mini: Non-social science research article
Coarse-graining bacterial diffusion in disordered media to surface states
Henry H. Mattingly
Full text
Bacterial motility in spatially structured environments impacts a variety of natural and engineering processes. Constructing models to predict, control, and design bacterial motility for these processes remains challenging because bacteria and active swimmers have complex interactions with surfaces and because the precise environment geometry is unknown. Here, we present a method for deriving bacterial diffusion coefficients in disordered media in terms of cell and environmental parameters. The approach abstracts the dynamics in the full geometry to “surface states,” which encode how cells interact with surfaces in the environment. Then, a long-time diffusion equation can be derived analytically from the state model. Applying this method to a run-and-tumble particle in a 2D Lorentz gas environment provides analytical predictions that show good agreement with particle simulations. Like past studies, we observe that the diffusivity depends nonmonotonically on the cell’s run length. Using the analytical expressions, we derive the optimal run length, revealing an intuitive dependence on environmental length scales. Furthermore, we find that rescaling length and time by the average distance and time between trap events collapses all of the diffusivities onto a single curve, which we derive analytically. Thus, our approach extracts interpretable, macroscopic diffusive behavior from complex microscopic dynamics, and provides tools and intuitions for understanding bacterial diffusion in disordered media.
GPT-4o mini: Non-social science research article
Climate change amplifies neurotoxic methylmercury threat to Asian fish consumers
Mengjie Wu, Xinda Wu, Alfonso Saiz-Lopez, Paul J. Blanchfield, Hongqiang Ren, Huan Zhong
Full text
Climate change is intricately influencing the accumulation of neurotoxic methylmercury (MeHg) in human food webs, potentially leading to uneven exposure risks across regions. Here, we reveal that climate change will elevate MeHg risks in China, with implications for regional inequalities in Asia through a climate-mercury-food-health nexus. Using a compiled fish mercury dataset from 13,000 samples and machine learning, we find that freshwater wild fish—an essential component of the Asian diet—is an underappreciated MeHg source. Specifically, MeHg concentrations in freshwater wild fish are 2.9 to 6.2 times higher than in freshwater farmed fish and 1.7 times higher than in marine wild fish. Individual climate factors influence MeHg accumulation differently, while their combined effects significantly increase MeHg concentrations in freshwater wild fish. Under SSP2–4.5 and SSP5–8.5 by 2031 to 2060, national average MeHg concentrations in freshwater wild fish are projected to increase by about 60%, adding a maximum annual economic loss of US$18 million (2022 USD) from intelligence quotient decrements in Chinese newborns. This loss may vary regionally within China and among Asian countries, disproportionately affecting less developed areas. Coordinating climate action with mercury emission reduction strategies could mitigate these overlooked regional risks, reduce regional inequalities in food safety, and ultimately contribute to sustainable development.
GPT-4o mini: Non-social science research article
Striking the balance: Complexity, simplicity, and credibility in mathematical biology
Cristobal Rodero, Steven A. Niederer
Full text
GPT-4o mini: Non-social science research article
Long-chain alkanes preserved in a Martian mudstone
Caroline Freissinet, Daniel P. Glavin, P. Douglas Archer, Samuel Teinturier, Arnaud Buch, Cyril Szopa, James M. T. Lewis, Amy J. Williams, Rafael Navarro-Gonzalez, Jason P. Dworkin, Heather. B. Franz, Maëva Millan, Jennifer L. Eigenbrode, R. E. Summons, Christopher H. House, Ross H. Williams, Andrew Steele, Ophélie McIntosh, Felipe Gómez, Benito Prats, Charles A. Malespin, Paul R. Mahaffy
Full text
Organic molecules preserved in ancient Martian rocks provide a critical record of the past habitability of Mars and could be chemical biosignatures. Experiments conducted by the Sample Analysis at Mars instrument onboard the Curiosity rover have previously reported several classes of indigenous chlorinated and sulfur-containing organic compounds in Gale crater sedimentary rocks, with chemical structures of up to six carbons. Here, we report the detection of decane (C 10 H 22 ), undecane (C 11 H 24 ), and dodecane (C 12 H 26 ) at the tens of pmol level, released from the Cumberland drilled mudstone sample, using a modified SAM analytical procedure optimized for the detection of larger organic molecules. Laboratory experiments support the hypothesis that the alkanes detected were originally preserved in the mudstone as long-chain carboxylic acids. The origin of these molecules remains uncertain, as they could be derived from either abiotic or biological sources.
GPT-4o mini: Non-social science research article
Central TYK2 inhibition identifies TYK2 as a key neuroimmune modulator
Tyler P. Molitor, Genki Hayashi, Mei-Yao Lin, Carissa J. Dunn, Nathan G. Peterson, Robert G. Poston, Michael P. Kurnellas, David A. Traver, Seona Patel, Zeynep Akgungor, Virginia Leonardi, Colizel Lewis, Joshua S. Segales, Dylan S. Bennett, Anh P. Truong, Manjari Dani, Swati Naphade, Jamie K. Wong, Annie E. McDermott, Sarah M. Kovalev, Gillian L. Ciaccio, Saud A. Sadiq, Zhonghua Pei, Stephen Wood, Arash Rassoulpour
Full text
GWAS have identified tyrosine kinase 2 (TYK2) variants in multiple inflammatory disorders, specifically a protective hypomorphic TYK2 allele (P1104A) in multiple sclerosis (MS). Impaired TYK2 signaling within the central nervous system (CNS) may impart the protective effects of TYK2 P1104A allele in MS. We deployed brain-penetrant TYK2 inhibitors (cTYK2i) alongside the peripherally restricted TYK2 inhibitor (pTYK2i; BMS-986165) to untangle the contributions of central TYK2 inhibition in diverse models of neuroinflammation. While pTYK2i had little impact, cTYK2i reduced clinical score, lymphoid cell infiltration, and cytokines/chemokines in experimental autoimmune encephalomyelitis (EAE). Microglial activation was attenuated in cTYK2i-treated EAE spinal cords and circulating neurofilament light (NfL) was reduced in plasma and cerebral spinal fluid (CSF). Additionally, cTYK2i was protective in an antibody-mediated mouse model of primary progressive MS (PPMS). Finally, we demonstrate TYK2 inhibition has a robust impact on a unique subset of activated astrocytes termed Interferon-Responsive-Reactive-Astrocytes (IRRA). The data presented herein identify a key role for CNS TYK2 signaling in regulating neuroinflammation and solidify TYK2 as a potential therapeutic target for MS.
GPT-4o mini: Non-social science research article
Elevated extinction risk in over one-fifth of native North American pollinators
Tara Cornelisse, David W. Inouye, Rebecca E. Irwin, Sarina Jepsen, Jonathan R. Mawdsley, Margaret Ormes, Jaret Daniels, Diane M. Debinski, Terry Griswold, John Klymko, Michael C. Orr, Leif Richardson, Nicole Sears, Dale Schweitzer, Bruce E. Young
Full text
Pollinators are critical for food production and ecosystem function. Although native pollinators are thought to be declining, the evidence is limited. This first, taxonomically diverse assessment for mainland North America north of Mexico reveals that 22.6% (20.6 to 29.6%) of the 1,579 species in the best-studied vertebrate and insect pollinator groups have elevated risk of extinction. All three pollinating bat species are at risk and bees are the insect group most at risk (best estimate, 34.7% of 472 species assessed, range 30.3 to 43.0%). Substantial numbers of butterflies (19.5% of 632 species, range 19.1 to 21.0%) and moths (16.1% of 142 species, range 15.5 to 19.0%) are also at risk, with flower flies (14.7% of 295 species, range 11.5 to 32.9%), beetles (12.5% of 18 species, range 11.1 to 22.2%), and hummingbirds (0% of 17 species) more secure. At-risk pollinators are concentrated where diversity is highest, in the southwestern United States. Threats to pollinators vary geographically: climate change in the West and North, agriculture in the Great Plains, and pollution, agriculture, and urban development in the East. Woodland, shrubland/chaparral, and grassland habitats support the greatest numbers of at-risk pollinators. Strategies for improving pollinator habitat are increasingly available, and this study identifies species, habitats, and threats most in need of conservation actions at state, provincial, territorial, national, and continental levels.
A national megastudy shows that email nudges to elementary school teachers boost student math achievement, particularly when personalized
Angela L. Duckworth, Ahra Ko, Katherine L. Milkman, Joseph S. Kay, Eugen Dimant, Dena M. Gromet, Aden Halpern, Youngwoo Jung, Madeline K. Paxson, Ramon A. Silvera Zumaran, Ron Berman, Ilana Brody, Colin F. Camerer, Elizabeth A. Canning, Hengchen Dai, Marcos Gallo, Hal E. Hershfield, Matthew D. Hilchey, Ariel Kalil, Kathryn M. Kroeper, Amy Lyon, Benjamin S. Manning, Nina Mazar, Michelle Michelini, Susan E. Mayer, Mary C. Murphy, Philip Oreopoulos, Sharon E. Parker, Renante Rondina, Dilip Soman, Christophe Van den Bulte
Full text
In response to the alarming recent decline in US math achievement, we conducted a national megastudy in which 140,461 elementary school teachers who collectively taught 2,992,027 students were randomly assigned to receive a variety of behaviorally informed email nudges aimed at improving students’ progress in math. Specifically, we partnered with the nonprofit educational platform Zearn Math to compare the impact of 15 different interventions with a reminder-only megastudy control condition. All 16 conditions entailed weekly emails delivered to teachers over 4-wk in the fall of 2021. The best-performing intervention, which encouraged teachers to log into Zearn Math for an updated report on how their students were doing that week, produced a 5.06% increase in students’ math progress (3.30% after accounting for the winner’s curse). In exploratory analyses, teachers who received any behaviorally informed email nudge (vs. a reminder-only megastudy control) saw their students’ math progress boosted by an average of 1.89% during the 4-wk intervention period; emails referencing personalized data (i.e., classroom-specific statistics) outperformed emails that did not by 2.26%. While small in size, these intervention effects were consistent across school socioeconomic status and school type (public, private, etc.) and, further, persisted in the 8-wk post-intervention period. Collectively, these findings underscore both how difficult it is to change behavior and the need for large-scale, rigorous, empirical research of the sort undertaken in this megastudy.
Superficial auditory (dis)fluency biases higher-level social judgment
Robert Walter-Terrill, Joan Danielle K. Ongchoco, Brian J. Scholl
Full text
When talking to other people, we naturally form impressions based not only on what they say but also on how they say it—e.g., how confident they sound. In modern life, however, the sounds of voices are often determined not only by intrinsic qualities (such as vocal anatomy) but also by extrinsic properties (such as videoconferencing microphone quality). Here, we show that such superficial auditory properties can have surprisingly deep consequences for higher-level social judgments. Listeners heard short narrated passages (e.g., from job application essays) and then made various judgments about the speakers. Critically, the recordings were modified to simulate different microphone qualities, while carefully equating listeners’ comprehension of the words. Though the manipulations carried no implications about the speakers themselves, common disfluent auditory signals (as in “tinny” speech) led to decreased judgments of intelligence, hireability, credibility, and romantic desirability. These effects were robust across speaker gender and accent, and they occurred for both human and clearly artificial (computer-synthesized) speech. Thus, just as judgments from written text are influenced by factors such as font fluency, judgments from speech are not only based on its content but also biased by the superficial vehicle through which it is delivered. Such effects may become more relevant as daily communication via videoconferencing becomes increasingly widespread.
Climate change impacts have potentially big repercussions for kids’ education
Saima Sidik
Full text
Social control drove ant evolution
Timothy A. Linksvayer
Full text
Most Christian American religious leaders silently believe in climate change, and informing their congregation can help open dialogue
Stylianos Syropoulos, Gregg Sparkman
Full text
Religious leaders shape the attitudes and beliefs of their congregations. In a nationally representative sample of U.S. religious leaders ( N = 1,600), the majority of which were of a Christian faith, we find that nearly 90% believe in anthropogenic climate change to some degree. From this 90%, a total of 60% believe humans play a major role and an additional 30% believe they play a role, but a more minor one. Yet roughly half have never discussed it with their congregation, and only a quarter have mentioned it more than once or twice. In a sample of Christian Americans representative of the proportions of major national denominations ( N = 987), we find that Christians underestimate the prevalence of their leaders who believe in climate change by 39 to 45 percentage points. Conversely, having a religious leader who talks about climate change predicts greater willingness to discuss it with fellow churchgoers and attend climate events. In an experimental intervention on another sample matching major Christian American denomination ( N = 959), we find that providing the actual consensus level of religious leaders’ belief in climate change reduces congregants’ misperception of religious leaders, increases their perception that other church members believe in and are open to discussing climate change, and leads Christians to believe that taking climate action is consistent with their church’s values while voting for politicians who will not take climate action is not.
The narrow search effect and how broadening search promotes belief updating
Eugina Leung, Oleg Urminsky
Full text
Information search platforms, from Google to AI-assisted search engines, have transformed information access but may fail to promote a shared factual foundation. We demonstrate that the combination of users’ prior beliefs influencing their search terms and the narrow scope of search algorithms can limit belief updating from search. We test this “narrow search effect” across 21 studies (14 preregistered) using various topics (e.g., health, financial, societal, political) and platforms (e.g., Google, ChatGPT, AI-powered Bing, our custom-designed search engine and AI chatbot interfaces). We then test user-based and algorithm-based interventions to counter the “narrow search effect” and promote belief updating. Studies 1 to 5 show that users’ prior beliefs influence the direction of the search terms, thereby generating narrow search results that limit belief updating. This effect persists across various domains (e.g., beliefs related to coronavirus, nuclear energy, gas prices, crime rates, bitcoin, caffeine, and general food or beverage health concerns; Studies 1a to 1b, 2a to 2g, 3, 4), platforms (e.g., Google—Studies 1a to 1b, 2a to 2g, 4, 5; ChatGPT, Study 3), and extends to consequential choices (Study 5). Studies 6 and 7 demonstrate the limited efficacy of prompting users to correct for the impact of narrow searches on their beliefs themselves. Using our custom-designed search engine and AI chatbot interfaces, Studies 8 and 9 show that modifying algorithms to provide broader results can encourage belief updating. These findings highlight the need for a behaviorally informed approach to the design of search algorithms.

Science

GPT-4o mini: Non-social science research article
Full freedom-of-motion actuators as advanced haptic interfaces
Kyoung-Ho Ha, Jaeyoung Yoo, Shupeng Li, Yuxuan Mao, Shengwei Xu, Hongyuan Qi, Hanbing Wu, Chengye Fan, Hanyin Yuan, Jin-Tae Kim, Matthew T. Flavin, Seonggwang Yoo, Pratyush Shahir, Sangjun Kim, Hak-Young Ahn, Edward Colgate, Yonggang Huang, John A. Rogers
Full text
The sense of touch conveys critical environmental information, facilitating object recognition, manipulation, and social interaction, and can be engineered through haptic actuators that stimulate cutaneous receptors. An unfulfilled challenge lies in haptic interface technologies that can engage all the various mechanoreceptors in a programmable, spatiotemporal fashion across large areas of the body. Here, we introduce a small-scale actuator technology that can impart omnidirectional, superimposable, dynamic forces to the surface of skin, as the basis for stimulating individual classes of mechanoreceptors or selected combinations of them. High-bit haptic information transfer and realistic virtual tactile sensations are possible, as illustrated through human subject perception studies in extended reality applications that include advanced hand navigation, realistic texture reproduction, and sensory substitution for music perception.
GPT-4o mini: Non-social science research article
A geographic history of human genetic ancestry
Michael C. Grundler, Jonathan Terhorst, Gideon S. Bradburd
Full text
Describing the distribution of genetic variation across individuals is a fundamental goal of population genetics. We present a method that capitalizes on the rich genealogical information encoded in genomic tree sequences to infer the geographic locations of the shared ancestors of a sample of sequenced individuals. We used this method to infer the geographic history of genetic ancestry of a set of human genomes sampled from Europe, Asia, and Africa, accurately recovering major population movements on those continents. Our findings demonstrate the importance of defining the spatiotemporal context of genetic ancestry when describing human genetic variation and caution against the oversimplified interpretations of genetic data prevalent in contemporary discussions of race and ancestry.
GPT-4o mini: Non-social science research article
A wheat tandem kinase and NLR pair confers resistance to multiple fungal pathogens
Ping Lu, Gaohua Zhang, Jing Li, Zhen Gong, Gaojie Wang, Lingli Dong, Huaizhi Zhang, Guanghao Guo, Min Su, Ke Wang, Yueming Wang, Keyu Zhu, Qiuhong Wu, Yongxing Chen, Miaomiao Li, Baoge Huang, Beibei Li, Wenling Li, Lei Dong, Yikun Hou, Xuejia Cui, Hongkui Fu, Dan Qiu, Chengguo Yuan, Hongjie Li, Jian-Min Zhou, Guan-Zhu Han, Yuhang Chen, Zhiyong Liu
Full text
Tandem kinase proteins underlie the innate immune systems of cereal plants, but how they initiate plant immune responses remains unclear. This report identifies wheat protein wheat tandem NBD 1 (WTN1), a noncanonical nucleotide-binding leucine-rich repeat (NLR) receptor featuring tandem nucleotide binding adaptor shared by APAF-1, plant R proteins, and CED-4 (NB-ARC) domains, required for WTK3-mediated disease resistance. Both WTK3 and its allelic variant Rwt4—known for conferring resistance to wheat powdery mildew and blast, respectively—are capable of recognizing the blast effector PWT4. They activate WTN1 to form calcium-permeable channels, akin to ZAR1 and Sr35. Thus, tandem kinase proteins and their associated NLRs operate as “sensor-executor” pairs against fungal pathogens. Additionally, evolutionary analyses reveal a coevolutionary trajectory of the tandem kinase-NLR module, highlighting their cooperative role in triggering plant immunity.
GPT-4o mini: Non-social science research article
A wheat tandem kinase activates an NLR to trigger immunity
Renjie Chen, Jian Chen, Oliver R. Powell, Megan A. Outram, Taj Arndell, Karthick Gajendiran, Yan L. Wang, Jibril Lubega, Yang Xu, Michael A. Ayliffe, Cheryl Blundell, Melania Figueroa, Jana Sperschneider, Thomas Vanhercke, Kostya Kanyuka, Dingzhong Tang, Guitao Zhong, Catherine Gardener, Guotai Yu, Spyridon Gourdoupis, Ɓukasz Jaremko, Oadi Matny, Brian J. Steffenson, Willem H. P. Boshoff, Wilku B. Meyer, Stefan T. Arold, Peter N. Dodds, Brande B. H. Wulff
Full text
The role of nucleotide-binding leucine-rich repeat (NLR) receptors in plant immunity is well studied, but the function of a class of tandem kinases (TKs) that confer disease resistance in wheat and barley remains unclear. In this study, we show that the SR62 locus is a digenic module encoding the Sr62 TK TK and an NLR (Sr62 NLR ), and we identify the corresponding AvrSr62 effector. AvrSr62 binds to the N-terminal kinase 1 of Sr62 TK , triggering displacement of kinase 2, which activates Sr62 NLR . Modeling and mutation analysis indicated that this is mediated by overlapping binding sites (i) on kinase 1 for binding AvrSr62 and kinase 2 and (ii) on kinase 2 for binding kinase 1 and Sr62 NLR . Understanding this two-component resistance complex may help engineering and breeding plants for durable resistance.
GPT-4o mini: Non-social science research article
Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety
Zhenggang Zhu, Rong Gong, Vicente Rodriguez, Kathleen T. Quach, Xinyu Chen, Scott M. Sternson
Full text
Hedonic eating is defined as food consumption driven by palatability without physiological need. However, neural control of palatable food intake is poorly understood. We discovered that hedonic eating is controlled by a neural pathway from the peri–locus ceruleus to the ventral tegmental area (VTA). Using photometry-calibrated optogenetics, we found that VTA dopamine (VTA DA ) neurons encode palatability to bidirectionally regulate hedonic food consumption. VTA DA neuron responsiveness was suppressed during food consumption by semaglutide, a glucagon-like peptide receptor 1 (GLP-1R) agonist used as an antiobesity drug. Mice recovered palatable food appetite and VTA DA neuron activity during repeated semaglutide treatment, which was reversed by consumption-triggered VTA DA neuron inhibition. Thus, hedonic food intake activates VTA DA neurons, which sustain further consumption, a mechanism that opposes appetite reduction by semaglutide.
GPT-4o mini: Non-social science research article
Running a genetic stop sign accelerates oxygen metabolism and energy production in horses
Gianni M. Castiglione, Xin Chen, Zhenhua Xu, Nadir H. Dbouk, Anamika A. Bose, David Carmona-Berrio, Emiliana E. Chi, Lingli Zhou, Tatiana N. Boronina, Robert N. Cole, Shirley Wu, Abby D. Liu, Thalia D. Liu, Haining Lu, Ted Kalbfleisch, David Rinker, Antonis Rokas, Kyla Ortved, Elia J. Duh
Full text
Horses are among nature’s greatest athletes, yet the ancestral molecular adaptations fueling their energy demands are poorly understood. Within a clinically important pathway regulating redox and metabolic homeostasis (NRF2/KEAP1), we discovered an ancient mutation—conserved in all extant equids—that increases mitochondrial respiration while decreasing tissue-damaging oxidative stress. This mutation is a de novo premature opal stop codon in KEAP1 that is translationally recoded into a cysteine through previously unknown mechanisms, producing an R15C mutation in KEAP1 that is more sensitive to electrophiles and reactive oxygen species. This recoding enables increased NRF2 activity, which enhances mitochondrial adenosine 5â€Č-triphosphate production and cellular resistance to oxidative damage. Our study illustrates how recoding of a de novo stop codon, a strategy thought restricted to viruses, can facilitate adaptation in vertebrates.
GPT-4o mini: Non-social science research article
A high-temperature nanostructured Cu-Ta-Li alloy with complexion-stabilized precipitates
B. C. Hornbuckle, J. A. Smeltzer, S. Sharma, S. Nagar, C. J. Marvel, P. R. Cantwell, M. P. Harmer, K. Solanki, K. A. Darling
Full text
We present a bulk nanocrystalline copper alloy that can operate at near-melting temperatures with minimal coarsening and creep deformation. The thermal stability of the Cu-3Ta-0.5Li atomic % (at %) alloy is attributed to coherent, ordered L1 2 Cu 3 Li precipitates surrounded by a tantalum-rich atomic bilayer phase boundary complexion. Adding 0.5 at % lithium to the immiscible Cu-Ta system changes the morphology of the nanoscale precipitates from spherical to cuboidal while simultaneously tailoring the phase boundary. The resultant complexion-stabilized nanoscale precipitates provide excellent thermal stability, strength, and creep resistance. The underlying alloy design principles may guide the development of next-generation copper alloys for high-temperature applications such as heat exchangers.
GPT-4o mini: Non-social science research article
Abrupt sea level rise and Earth’s gradual pole shift reveal permanent hydrological regime changes in the 21st century
Ki-Weon Seo, Dongryeol Ryu, Taehwan Jeon, Kookhyoun Youm, Jae-Seung Kim, Earthu H. Oh, Jianli Chen, James S. Famiglietti, Clark R. Wilson
Full text
Rising atmospheric and ocean temperatures have caused substantial changes in terrestrial water circulation and land surface water fluxes, such as precipitation and evapotranspiration, potentially leading to abrupt shifts in terrestrial water storage. The European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis v5 (ERA5) soil moisture (SM) product reveals a sharp depletion during the early 21st century. During the period 2000 to 2002, soil moisture declined by approximately 1614 gigatonnes, much larger than Greenland’s ice loss of about 900 gigatonnes (2002–2006). From 2003 to 2016, SM depletion continued, with an additional 1009-gigatonne loss. This depletion is supported by two independent observations of global mean sea level rise (~4.4 millimeters) and Earth’s pole shift (~45 centimeters). Precipitation deficits and stable evapotranspiration likely caused this decline, and SM has not recovered as of 2021, with future recovery unlikely under present climate conditions.
GPT-4o mini: Non-social science research article
Complex-frequency excitations in photonics and wave physics
Seunghwi Kim, Alex Krasnok, Andrea AlĂč
Full text
Closed, lossless optical cavities are characterized by a Hamiltonian that obeys Hermiticity, resulting in strictly real-valued resonance frequencies. By contrast, non-Hermitian wave systems are characterized by Hamiltonians with poles and zeros at complex frequencies, whose control through precise engineering of material loss and gain can lead to exotic scattering phenomena. Notably, excitation signals that oscillate at complex-valued frequencies can mimic the emergence of gain and loss, facilitating access to these non-Hermitian responses without material modifications. These findings have been advancing the fundamental understanding of wave-matter interactions and are enabling breakthroughs in metamaterials, imaging, sensing, and computing. This Review examines theoretical advances and experimental discoveries in this emerging field, demonstrating how tailored time-domain excitations offer new opportunities for wave manipulation and control.
GPT-4o mini: Non-social science research article
Chromatin accessibility landscape of mouse early embryos revealed by single-cell NanoATAC-seq2
Mengyao Li, Zhenhuan Jiang, Xueqiang Xu, Xinglong Wu, Yun Liu, Kexuan Chen, Yuhan Liao, Wen Li, Xiao Wang, Yuqing Guo, Bo Zhang, Lu Wen, Kehkooi Kee, Fuchou Tang
Full text
In mammals, fertilized eggs undergo genome-wide epigenetic reprogramming to generate the organism. However, our understanding of epigenetic dynamics during preimplantation development at single-cell resolution remains incomplete. Here, we developed scNanoATAC-seq2, a single-cell assay for transposase-accessible chromatin using long-read sequencing for scarce samples. We present a detailed chromatin accessibility landscape of mouse preimplantation development, revealing distinct chromatin signatures in the epiblast, primitive endoderm, and trophectoderm during lineage segregation. Differences between zygotes and two-cell embryos highlight reprogramming in chromatin accessibility during the maternal-to-zygotic transition. Single-cell long-read sequencing enables in-depth analysis of chromatin accessibility in noncanonical imprinting, imprinted X chromosome inactivation, and low-mappability genomic regions, such as repetitive elements and paralogs. Our data provide insights into chromatin dynamics during mammalian preimplantation development and lineage differentiation.
GPT-4o mini: Non-social science research article
Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins
Aakriti Jain, Isaac Heremans, Gilles Rademaker, Tyler C. Detomasi, Peter Rohweder, Dashiell Anderson, Justin Zhang, Grace A. Hernandez, Suprit Gupta, Teresa von Linde, Mike Lange, Martina Spacci, Jiayi Luo, Y. Rose Citron, James A. Olzmann, David W. Dawson, Charles S. Craik, Guido Bommer, Rushika M. Perera, Roberto Zoncu
Full text
Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic datasets, we identified lysosomal leucine aminopeptidase (LyLAP; formerly phospholipase B domain–containing 1) as the hydrolase most tightly associated with elevated endocytosis. Untargeted metabolomics and biochemical reconstitution demonstrated that LyLAP is a processive monoaminopeptidase with preference for amino-terminal leucine. This activity was necessary and sufficient for the breakdown of hydrophobic transmembrane domains. LyLAP was up-regulated in pancreatic ductal adenocarcinoma (PDA), which relies on macropinocytosis for nutrient uptake. In PDA cells, LyLAP ablation led to the buildup of undigested hydrophobic peptides, lysosomal membrane damage, and growth inhibition. Thus, LyLAP enables lysosomal degradation of membrane proteins and protects lysosomal integrity in highly endocytic cancer cells.
GPT-4o mini: Non-social science research article
Selective filtering of photonic quantum entanglement via anti–parity-time symmetry
Mahmoud A. Selim, Max Ehrhardt, Yuqiang Ding, Hediyeh M. Dinani, Qi Zhong, Armando Perez‐Leija, ƞahin K. Özdemir, Matthias Heinrich, Alexander Szameit, Demetrios N. Christodoulides, Mercedeh Khajavikhan
Full text
Entanglement is a key resource for quantum computing, sensing, and communication, but it is susceptible to decoherence. To address this, research in quantum optics has explored filtering techniques such as photon ancillas and Rydberg atom blockade to restore entangled states. We introduce an approach to entanglement retrieval that exploits the features of non-Hermitian systems. By designing an anti–parity-time two-state guiding configuration, we demonstrate efficient extraction of entanglement from any input state. This filter is implemented on a lossless waveguide network and achieves near-unity fidelity under single- and two-photon excitation and is scalable to higher photon levels, remaining robust against decoherence during propagation. Our results offer an approach to using non-Hermitian symmetries to address central challenges in quantum technologies.
GPT-4o mini: Non-social science research article
Isotopic and compositional constraints on the source of basalt collected from the lunar farside
Xiaochao Che, Tao Long, Alexander Nemchin, Shiwen Xie, Le Qiao, Zengsheng Li, Yiyi Ban, Runlong Fan, Chun Yang, Dunyi Liu
Full text
Volcanism on the Moon has produced surface basalt deposits, which record lunar interior processes. The Chang’e-6 mission retrieved samples from the South Pole–Aitken basin (SPA) on the Moon’s far side. We analyzed basalt fragments collected by Chang’e-6 and found that their composition resembles that of low-titanium basalts previously sampled by the Apollo missions. Uranium-lead (U-Pb) dating indicated a basalt age of 2823.0 ± 5.9 million years and a source 238 U/ 204 Pb ratio (ÎŒ-value) of 480 ± 56. This high ÎŒ-value indicates that the source contained materials that formed during the late stages of lunar magma ocean (LMO) crystallization. The results are consistent with the LMO model, but the Chang’e-6 basalt deviates from the trend in Apollo mission samples of younger basalts having higher ÎŒ-values. We suggest that this indicates post-LMO modification of the mantle by the SPA impact.
GPT-4o mini: Non-social science research article
Epithelial polarization by the planar cell polarity complex is exclusively non–cell autonomous
Lena P. Basta, Bradley W. Joyce, Eszter Posfai, Danelle Devenport
Full text
For cells to polarize collectively along a tissue plane, asymmetrically localized planar cell polarity (PCP) complexes must form intercellular contacts between neighboring cells. Yet, it is unknown whether asymmetric segregation of PCP complexes requires cell-cell contact, or if cell autonomous, antagonistic interactions are sufficient for polarization. To test this, we generated mouse chimeras consisting of dual PCP-reporter cells mixed with unlabeled cells that cannot form PCP bridges. In the absence of intercellular interactions, PCP proteins failed to polarize cell autonomously. Rather, PCP-mediated contacts along single cell-cell interfaces were sufficient to sort PCP components to opposite sides of the junction, independent of junction orientation. Thus, intercellular binding of PCP complexes is the critical step that initiates sorting of opposing PCP complexes to generate asymmetry.
GPT-4o mini: Non-social science research article
Hippocampal encoding of memories in human infants
Tristan S. Yates, Jared Fel, Dawoon Choi, Juliana E. Trach, Lillian Behm, Cameron T. Ellis, Nicholas B. Turk-Browne
Full text
Humans lack memories for specific events from the first few years of life. We investigated the mechanistic basis of this infantile amnesia by scanning the brains of awake infants with functional magnetic resonance imaging while they performed a subsequent memory task. Greater activity in the hippocampus during the viewing of previously unseen photographs was related to later memory-based looking behavior beginning around 1 year of age, suggesting that the capacity to encode individual memories comes online during infancy. The availability of encoding mechanisms for episodic memory during a period of human life that is later lost from our autobiographical record implies that postencoding mechanisms, whereby memories from infancy become inaccessible for retrieval, may be more responsible for infantile amnesia.
GPT-4o mini: Non-social science research article
Regulatory T cells constrain T cells of shared specificity to enforce tolerance during infection
David E. J. Klawon, Nicole Pagane, Matthew T. Walker, Nicole K. Ganci, Christine H. Miller, Eric Gai, Donald M. Rodriguez, Bridgett K. Ryan-Payseur, Ryan K. Duncombe, Erin J. Adams, Mark Maienschein-Cline, Nancy E. Freitag, Ronald N. Germain, Harikesh S. Wong, Peter A. Savage
Full text
During infections, CD4 + Foxp3 + regulatory T (T reg ) cells must control autoreactive CD4 + conventional T (T conv ) cell responses against self-peptide antigens while permitting those against pathogen-derived “nonself” peptides. We defined the basis of this selectivity using mice in which T reg cells reactive to a single prostate-specific self-peptide were selectively depleted. We found that self-peptide–specific T reg cells were dispensable for the control of T conv cells of matched specificity at homeostasis. However, they were required to control such T conv cells and prevent autoimmunity toward the prostate after exposure to elevated self-peptide during infection. Notably, the T reg cell response to self-peptide did not affect protective T conv cell responses to a pathogen-derived peptide. Thus, self-peptide–specific T reg cells promoted self-nonself discrimination during infection by selectively controlling T conv cells of shared self-specificity.
Science abstract < 200 char.: Not a research article
ADHD, at 42
Nina Ockendon-Powell
Full text
Science abstract < 200 char.: Not a research article
Guiding science in China
Andrew Kennedy
Full text
Increasing emphasis on national priorities creates tension with curiosity-driven research
Science abstract < 200 char.: Not a research article
Mars rover detects long-chain carbon molecules
Paul Voosen
Full text
Fatty acid byproducts that Curiosity found in an ancient lakebed could be the remains of microbes—or not
Science abstract < 200 char.: Not a research article
Women-driven community education in Nepal
Arya Gautam, Sandesh Ghimire, Aashish R. Jha
Full text
Science abstract < 200 char.: Not a research article
News at a glance
Full text
Science abstract < 200 char.: Not a research article
Safety in the smoke
Warren Cornwall
Full text
Science abstract < 200 char.: Not a research article
How did cow flu start? Scientists still don’t know
Kai Kupferschmidt
Full text
One year later, how H5N1 spills over into dairy cattle—and how often—remains a mystery
Science abstract < 200 char.: Not a research article
In Science Journals
Melisa Yashinski, Leslie K. Ferrarelli, Marc S. Lavine, Madeleine Seale, Jake S. Yeston, Ekeoma Uzogara, Ian S. Osborne, Di Jiang, Stella M. Hurtley, Yevgeniya Nusinovich, Jesse Smith, Sacha Vignieri, Peter Stern, Corinne N. Simonti, Amos Matsiko, Orla Smith, Claire Olingy
Full text
Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
In the ashes
Warren Cornwall
Full text
After wildfires burned houses and brush alike in Los Angeles, researchers have mobilized to understand the health risks posed by urban conflagrations
Science abstract < 200 char.: Not a research article
U.S. cuts hamper disease surveillance worldwide
Jon Cohen
Full text
Many efforts to prevent outbreaks and track diseases are suddenly in limbo
Science abstract < 200 char.: Not a research article
New data fill long-standing gaps in the study of policing
Dean Knox, Jonathan Mummolo
Full text
Data show discrimination, but analysis must be more policy relevant
Science abstract < 200 char.: Not a research article
Furor over quantum computing claim heats up
Zack Savitsky
Full text
Physicists cast doubt on measurements said to show Microsoft chip uses exotic Majorana quasiparticles
Science abstract < 200 char.: Not a research article
The meaning of our meals How the World Eats: A Global Food Philosophy Julian Baggini Pegasus, 2025. 464 pp.
Stefania Pizzirani
Full text
A philosopher confronts how factors from culture to capitalism affect the foods we eat
Science abstract < 200 char.: Not a research article
In Other Journals
Caroline Ash, Corinne Simonti, Ian S. Osborne, Jelena Stajic, L. Bryan Ray, Priscilla N. Kelly, Jack Huang
Full text
Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
In Mexico, a whale of a controversy over gas port
Alexa Robles-Gil
Full text
Researchers want better studies of how planned LNG terminal would affect marine life
Science abstract < 200 char.: Not a research article
South Africa caught in new tsunami of NIH grant cuts
Jon Cohen, Sara Reardon
Full text
Agency moves to terminate nearly 1000 projects, including many involving “DEI” and LGBTQ health
Science abstract < 200 char.: Not a research article
Mapping a complex evolutionary history
Simon Gravel
Full text
Tracking the geographic origins of genetic ancestors reveals past human migrations
Science abstract < 200 char.: Not a research article
Beyond hedonic eating
Dana M. Small
Full text
A dopaminergic brain circuit drives food consumption in mice
Science abstract < 200 char.: Not a research article
Lined up for entanglement
Evgeny Moiseev, Kai Wang
Full text
A framework widely used in classical contexts provides new insights into solving an important challenge in quantum technology
Science abstract < 200 char.: Not a research article
AAAS names 2024 Fellows
Full text
Science abstract < 200 char.: Not a research article
Equitable access needed in clinical research
Gisa Dang, Christophe Perrin, Jennifer Furin
Full text
Science abstract < 200 char.: Not a research article
An end to human exceptionalism The Decline and Fall of the Human Empire: Why Our Species Is on the Edge of Extinction Henry Gee St. Martin’s Press, 2025. 288 pp.
Adrian Woolfson
Full text
Our species’ extinction is inevitable, argues a paleontologist
Science abstract < 200 char.: Not a research article
Romanian brown bear management regresses
Mihai I. Pop, Ruben Iosif, Barbara Promberger-FĂŒrpass, Silviu Chiriac, Ágnes Keresztesi, Laurentiu Rozylowicz, Viorel D. Popescu
Full text
Science abstract < 200 char.: Not a research article
Permanent shifts in the global water cycle
Luis Samaniego
Full text
Decades of terrestrial water-storage changes reveal an irreversible decline in soil moisture
Science abstract < 200 char.: Not a research article
The Moon is nearly as old as Earth
Paul Voosen
Full text
Studies of Apollo rocks push back Moon-forming collision by more than 100 million years
Science abstract < 200 char.: Not a research article
Poland’s border policies imperil river ecosystems
Ignacy Kitowski, Agnieszka Sujak, Mariusz Drygaƛ
Full text
Science abstract < 200 char.: Not a research article
My crisis Ph.D.
Paige Nicklas
Full text
Science abstract < 200 char.: Not a research article
Isolated atoms, but entangled
Guido Pupillo, Gavin Brennen
Full text
Confined light connects atomic qubits to enable networked quantum processors
Science abstract < 200 char.: Not a research article
Uncertainty abounds, what now? The Art of Uncertainty: How to Navigate Chance, Ignorance, Risk, and Luck David Spiegelhalter Norton, 2025. 336 pp.
Dov Greenbaum, Mark Gerstein
Full text
A statistician offers insight into risk, probability, and decision-making
Science abstract < 200 char.: Not a research article
New antibody studies boost hope for an HIV cure
Jon Cohen
Full text
Pioneering trials discover potential strategy to keep the virus in check after stopping antiretroviral treatment
Science abstract < 200 char.: Not a research article
News at a glance
Full text
High-frequency location data show that race affects citations and fines for speeding
Pradhi Aggarwal, Alec Brandon, Ariel Goldszmidt, Justin Holz, John A. List, Ian Muir, Gregory Sun, Thomas Yu
Full text
Prior research on racial profiling has found that in encounters with law enforcement, minorities are punished more severely than white civilians. Less is known about the causes of these encounters and their implications for our understanding of racial profiling. Using high-frequency location data of rideshare drivers in Florida ( N = 222,838 individuals), we estimate the effect of driver race on citations and fines for speeding using 19.3 million location pings. Compared with a white driver traveling the same speed, we find that racial or ethnic minority drivers are 24 to 33% more likely to be cited for speeding and pay 23 to 34% more money in fines. We find no evidence that accident and reoffense rates explain these estimates, which suggests that an animus against minorities underlies our results.

Science Advances

Generic title: Not a research article
Erratum for the Research Article: “Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy” by S. Li et al .
Full text
Generic title: Not a research article
Erratum for the Research Article: “Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell–based cartilage tissue engineering” by J. Lee et al .
Full text
GPT-4o mini: Non-social science research article
Particle-armored liquid robots
Hyobin Jeon, Keunhwan Park, Jeong-Yun Sun, Ho-Young Kim
Full text
It is challenging to emulate biological forms and functions with artificial machines: Fluidity and adaptability seen in cellular organisms, characterized by their ability to deform, split, merge, and engulf, are hard to recapitulate with traditional rigid robotic structures. A promising avenue to tackle this problem is harnessing the supreme deformability of liquids while providing stable yet flexible shells around them. Here, we report a highly robust liquid-particle composite, named a Particle-armored liquid roBot (PB), featuring a liquid blob coated with unusually abundant superhydrophobic particles. The enhanced deformability and structural stability of our millimetric PBs enable a range of versatile robotic functions, such as navigating through complex environments, engulfing and transporting cargoes, merging, and adapting to various environments. We use both theoretical analysis and experimental approaches to develop a framework for predicting the shape evolution, dynamics, and robotic functions of PBs. The forms and functions of our liquid robots mark an essential hallmark toward miniature biomachines that perform like cells.
GPT-4o mini: Non-social science research article
CD38-mediated metabolic reprogramming promotes the stability and suppressive function of regulatory T cells in tumor
Ishita Sarkar, Debashree Basak, Puspendu Ghosh, Anupam Gautam, Arpita Bhoumik, Praveen Singh, Anwesha Kar, Shaun Mahanti, Snehanshu Chowdhury, Lagnajita Chakraborty, Soumya Mondal, Ramanuj Mukherjee, Shikhar Mehrotra, Saikat Majumder, Shantanu Sengupta, Sandip Paul, Shilpak Chatterjee
Full text
In the tumor microenvironment (TME), regulatory T cells (T regs ) adapt their metabolism to thrive in low-glucose, high-lactate conditions, but the mechanisms remain unclear. Our study identifies CD38 as a key regulator of this adaptation by depleting nicotinamide adenine dinucleotide (oxidized form) (NAD + ), redirecting lactate-derived pyruvate toward phosphoenolpyruvate and bypassing the tricarboxylic acid (TCA) cycle. This prevents accumulation of α-ketoglutarate, which destabilizes T regs by inducing hypermethylation at the Foxp3 locus. Restoring NAD + with nicotinamide mononucleotide reverses this adaptation, pushing T regs back to the TCA cycle and reducing their suppressive function. In YUMM1.7 melanoma-bearing mice, small-molecule CD38 inhibition selectively destabilizes intratumoral T regs , sparking robust antitumor immunity. These findings reveal that targeting the CD38-NAD + axis disrupts T regs metabolic adaptation and offers a strategy to enhance antitumor responses.
GPT-4o mini: Non-social science research article
Evidence and quantification of memory effects in competitive first-passage events
Maxim Dolgushev, Toni Vieira Mendes, Benjamin Gorin, Kaili Xie, Nicolas Levernier, Olivier Bénichou, Hamid Kellay, Raphaël Voituriez, Thomas Guérin
Full text
Splitting probabilities quantify the likelihood of a given outcome out of competitive events. This key observable of random walk theory, historically introduced as the gambler’s ruin problem, is well understood for memoryless (Markovian) processes. However, in complex systems such as polymer fluids, the motion of a particle should typically be described as a process with memory, for which splitting probabilities are much less characterized analytically. Here, we introduce an analytical approach that provides the splitting probabilities for one-dimensional isotropic non-Markovian Gaussian processes with stationary increments, in the case of two targets. This analysis shows that splitting probabilities are controlled by the out-of-equilibrium trajectories observed after the first passage. This is directly evidenced in a prototypical experimental reaction scheme in viscoelastic fluids. These results are extended to d -dimensional processes in large confining volumes, opening a path toward the study of competitive events in complex media.
GPT-4o mini: Non-social science research article
A low-temperature, one-step synthesis for monazite can transform monazite into a readily usable advanced nuclear waste form
Yunping Zhoujin, Hunter B. Tisdale, Navindra Keerthisinghe, Gregory Morrison, Mark D. Smith, Joke Hadermann, Theodore M. Besmann, Jake Amoroso, Hans-Conrad zur Loye
Full text
It has been demonstrated that monazite-type materials are excellent candidates for nuclear waste forms, and hence, their facile synthesis is of great importance for the needed sequestration of existing nuclear waste. The synthesis of monazite, LaPO 4 , requires inconveniently high temperatures near 1000°C and generally involves the conversion of the presynthesized rhabdophane, LaPO 4 ‱nH 2 O, to the LaPO 4 monazite phase. During this structure transformation, the rhabdophane converts irreversibly to the thermodynamically stable monoclinic monazite structure. A low-temperature (185° to 260°C) mild hydrothermal acid-promoted synthesis of monazite is described that can both transform presynthesized rhabdophane or assemble reagents to the monoclinic monazite structure. The pH dependence of this reaction is detailed, and its applicability to the Ln PO 4 ( Ln  = La, Ce, Pr, Nd, Sm-Gd), Ca 0.5 Th 0.5 PO 4 , and Sr 0.5 Th 0.5 PO 4 systems is discussed. The crystal growth of Ca 0.5 Th 0.5 PO 4 and Sr 0.5 Th 0.5 PO 4 is described, and their crystal structures were reported. In situ x-ray diffraction studies, performed as a function of temperature, provide insight into the structure transformation process.
GPT-4o mini: Non-social science research article
Selective promotion of sensory innervation–mediated immunoregulation for tissue repair
Kaicheng Xu, Kaile Wu, Liang Chen, Yubin Zhao, Hengyuan Li, Nong Lin, Zhaoming Ye, Jianbin Xu, Donghua Huang, Xin Huang
Full text
Sensory innervation triggers the regenerative response after injury. However, dysfunction and impairment of sensory nerves, accompanied by excessive inflammation impede tissue regeneration. Consequently, specific induction of sensory innervation to mediate immunoregulation becomes a promising therapeutic approach. Herein, we developed a cell/drug-free strategy to selectively boost endogenous sensory innervation to harness immune responses for promoting tissue rehabilitation. Specifically, a dual-functional phage was constructed with a sensory nerve–homing peptide and a ÎČ-subunit of nerve growth factor (ÎČ-NGF)–binding peptide. These double-displayed phages captured endogenic ÎČ-NGF and localized to sensory nerves to promote sensory innervation. Furthermore, regarding bone regeneration, phage-loaded hydrogels achieved rapid sensory nerve ingrowth in bone defect areas. Mechanistically, sensory neurotization facilitated M2 polarization of macrophages through the Sema3A/XIAP/PAX6 pathway, thus decreasing the M1/M2 ratio to induce the dissipation of local inflammation. Collectively, these findings highlight the essential role of sensory innervation in manipulating inflammation and provide a conceptual framework based on neuroimmune interactions for promoting tissue regeneration.
GPT-4o mini: Non-social science research article
Emergence of a senescent and inflammatory pulmonary CD4 + T cell population prior to lung allograft failure
Sajad Moshkelgosha, Liran Levy, Shahideh Safavi, Sumiha Karunagaran, Gavin Wilson, Benjamin Renaud-Picard, Goodness Madu, Rashi Ramchandani, Jillian Oliver, Tatsuaki Watanabe, Ke Fan Bei, Betty Joe, Qixuan Li, Ella Huszti, May Cheung, David Hedley, Jonathan Yeung, Shaf Keshavjee, Tereza Martinu, Stephen Juvet
Full text
Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD), an alloimmune fibrotic process leading to death or retransplantation after a median of 6 years. Immunosuppression fails to prevent CLAD, suggesting the existence of drug-resistant alloimmune pathways. We used time-of-flight mass cytometry to identify cells enriched in the bronchoalveolar lavage of patients with subsequent acute lung allograft dysfunction (ALAD), a risk factor for CLAD. We show that CD4 + CD57 + PD1 + T cells emerge in stable patients, conferring risks for ALAD, CLAD, and death. These cells are senescent, secrete inflammatory cytokines, and fall into two oligoclonal subsets with putative cytotoxic and follicular helper functions. Last, they are associated with fibrosis in mouse and human lung allografts, where they localize near airway epithelium and B cells. Together, our findings reveal an inflammatory T cell population that predicts future lung allograft dysfunction and may represent a rational therapeutic target.
GPT-4o mini: Non-social science research article
Nanosecond-pulsed electroluminescence from high current–driven quantum-dot light-emitting diodes
Tianhong Zhou, Fengshou Tian, Shuming Chen
Full text
Ultrashort optical emission, with pulse duration ranging from nanoseconds to femtoseconds, is usually obtained from lasers. In this work, we achieve nanosecond-pulsed electroluminescence (EL) from a solution-processed fast-response quantum dot light-emitting diode (QLED). By modeling the QLED with a resistor-capacitor equivalent circuit and analyzing the transient current of the circuit, the dynamic of the carrier injection and transport process that fundamentally affects the transient EL of QLED is revealed, which helps to guide the optimization of fast-response QLED. Driven by a high current source, the optimized QLED can output stable and repeatable ultrashort EL with a pulse duration of 20 nanoseconds, a repetition rate of 50 kilohertz, and a high radiant exitance of 5.4 watts per square centimeter. Enabled by the nanosecond-pulsed EL, the developed QLED can be directly used as an instantaneous excitation source for time-resolved fluorescence spectroscopy. Meanwhile, its use as an exposure flash for high-speed imaging is also demonstrated.
GPT-4o mini: Non-social science research article
Distinct attentional characteristics of neurons with visual feature coding in the primate brain
Jie Zhang, Runnan Cao, Xiaocang Zhu, Huihui Zhou, Shuo Wang
Full text
Visual attention and object recognition are two critical cognitive functions that shape our perception of the world. While these neural processes converge in the temporal cortex, the nature of their interactions remains largely unclear. Here, we systematically investigated the interplay between visual attention and stimulus feature coding by training macaques to perform a free-gaze visual search task with natural stimuli. Recording from a large number of units across multiple brain areas, we found that units exhibiting visual feature coding showed stronger attentional modulation of responses and spike–local field potential coherence than units without feature coding. Across brain areas, attention directed toward search targets enhanced the neuronal pattern separation of stimuli, with this enhancement more pronounced for units encoding visual features. Together, our results suggest a complex interplay between visual feature and attention coding in the primate brain, likely driven by interactions between brain areas engaged in these processes.
GPT-4o mini: Non-social science research article
Proteogenomic discovery of RB1 -defective phenocopy in cancer predicts disease outcome, response to treatment, and therapeutic targets
Jacopo Iacovacci, Rachel Brough, Fatemeh Ahmadi Moughari, John Alexander, Harriet Kemp, Andrew N. J. Tutt, Rachael Natrajan, Christopher J. Lord, Syed Haider
Full text
Genomic defects caused by truncating mutations or deletions in the Retinoblastoma tumor suppressor gene ( RB1 ) are frequently observed in many cancer types leading to dysregulation of the RB pathway. Here, we propose an integrative proteogenomic approach that predicts cancers with dysregulation in the RB pathway. A subset of these cancers, which we term as “RBness,” lack RB1 genomic defects and yet phenocopy the transcriptional profile of RB1 -defective cancers. We report RBness as a pan-cancer phenomenon, associated with patient outcome and chemotherapy response in multiple cancer types, and predictive of CDK4/6 inhibitor response in estrogen-positive breast cancer. Using RNA interference and a CRISPR-Cas9 screen in isogenic models, we find that RBness cancers also phenocopy synthetic lethal vulnerabilities of cells with RB1 genomic defects. In summary, our findings suggest that dysregulation of the RB pathway in cancers lacking RB1 genomic defects provides a molecular rationale for how these cancers could be treated.
GPT-4o mini: Non-social science research article
Demographic bias of expert-level vision-language foundation models in medical imaging
Yuzhe Yang, Yujia Liu, Xin Liu, Avanti Gulhane, Domenico Mastrodicasa, Wei Wu, Edward J. Wang, Dushyant Sahani, Shwetak Patel
Full text
Advances in artificial intelligence (AI) have achieved expert-level performance in medical imaging applications. Notably, self-supervised vision-language foundation models can detect a broad spectrum of pathologies without relying on explicit training annotations. However, it is crucial to ensure that these AI models do not mirror or amplify human biases, disadvantaging historically marginalized groups such as females or Black patients. In this study, we investigate the algorithmic fairness of state-of-the-art vision-language foundation models in chest x-ray diagnosis across five globally sourced datasets. Our findings reveal that compared to board-certified radiologists, these foundation models consistently underdiagnose marginalized groups, with even higher rates seen in intersectional subgroups such as Black female patients. Such biases present over a wide range of pathologies and demographic attributes. Further analysis of the model embedding uncovers its substantial encoding of demographic information. Deploying medical AI systems with biases can intensify preexisting care disparities, posing potential challenges to equitable healthcare access and raising ethical questions about their clinical applications.
GPT-4o mini: Non-social science research article
Assessing cancer therapeutic efficacy in vivo using [ 2 H 7 ]glucose deuterium metabolic imaging
Mario C. Chang, Vinay R. Malut, Rohit Mahar, Anna Rushin, Marc A. McLeod, Geraldine L. Pierre, Indu R. Malut, Stephen J. Staklinski, Max E. Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D. Rao, Brian K. Law, Michael S. Kilberg, James H. P. Collins, Vikram D. Kodibagkar, James A. Bankson, Ralph J. DeBerardinis, Matthew E. Merritt
Full text
Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[ 18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6- 2 H 2 ]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [ 2 H 7 ]glucose. Imaging 2 H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or anti-glycolytic BRAFi and MEKi therapy, and contralateral healthy tissue. Control tumors generated the most 2 H-signal and HDO. To our knowledge this is the first application of DMRI with [ 2 H 7 ]glucose for tumoral treatment monitoring. This approach demonstrates HDO as a marker of tumor glucose utilization and suggests translational capability in humans due to its safety, noninvasiveness, and suitability for serial monitoring.
GPT-4o mini: Non-social science research article
Macrophage-targeted Mms6 mRNA-lipid nanoparticles promote locomotor functional recovery after traumatic spinal cord injury in mice
Chunyan Fu, Xiaoqin Jin, Kangfan Ji, Ke Lan, Xingjia Mao, Zhaobo Huang, Jian Chen, Fengdong Zhao, Pengfei Li, Xuefei Hu, Liwen Sun, Ning Lu, Jinjie Zhong, Yingying Chen, Linlin Wang
Full text
Traumatic spinal cord injury (SCI) causes severe central nervous system damage. M2 macrophages within the lesion are crucial for SCI recovery. Our previous research revealed that M2 macrophages transfected with magnetotactic bacteria–derived Mms6 gene can resist ferroptosis and enhance SCI recovery. To address the limitations of M2 macrophage transplantation, we developed lipid nanoparticles (LNPs) encapsulating Mms6 mRNA targeting macrophages ( Mms6 mRNA-PS/LNPs). The targeting efficiency and therapeutic effect of these LNPs in SCI mice were evaluated. Intravenous administration of Mms6 mRNA-PS/LNPs delivered more Mms6 mRNAs to lesion-site macrophages than those in the Mms6 mRNA-LNP group, which resulted in enhancing motor function recovery, reducing lesion area and scar formation, and promoting neuronal survival and nerve fiber repair. These effects were nullified when macrophages were depleted. These findings suggest that macrophage-targeted delivery of Mms6 mRNA is a promising therapeutic strategy for promoting spinal cord repair and motor function recovery in patients with traumatic SCI.
GPT-4o mini: Non-social science research article
A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells
Mariana Bustamante Eduardo, Gannon Cottone, Curtis W. McCloskey, Shiyu Liu, Flavio R. Palma, Maria Paula Zappia, Abul B.M.M.K. Islam, Peng Gao, Joel Setya, Saya Dennis, Hongyu Gao, Qian Zhang, Xiaoling Xuei, Yuan Luo, Jason Locasale, Marcelo G. Bonini, Rama Khokha, Maxim V. Frolov, Elizaveta V. Benevolenskaya, Navdeep S. Chandel, Seema A. Khan, Susan E. Clare
Full text
Lipid metabolism and the serine, one-carbon, glycine (SOG) and methionine pathways are independently and significantly correlated with estrogen receptor–negative breast cancer (ERneg BC). Here, we propose a link between lipid metabolism and ERneg BC through phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the de novo serine pathway. We demonstrate that the metabolism of the paradigmatic medium-chain fatty acid octanoic acid leads to a metabolic shift toward the SOG and methionine pathways. PHGDH plays a role in both the forward direction, contributing to the production of S-adenosylmethionine, and the reverse direction, generating the oncometabolite 2-hydroxyglutarate, leading to epigenomic reprogramming and phenotypic plasticity. The methionine cycle is closely linked to the transsulfuration pathway. Consequently, we observe that the shift increases the antioxidant glutathione, which mitigates reactive oxygen species (ROS), enabling survival of a subset of cells that have undergone DNA damage. These metabolic changes contribute to several hallmarks of cancer.
GPT-4o mini: Non-social science research article
Simultaneous head-mounted imaging of neural and hemodynamic activities at high spatiotemporal resolution in freely behaving mice
Ningbo Chen, Zhiqiang Xu, Zheng Song, Jiuling Liao, Hongdong Zhang, Jiahao Li, Taofeng Wu, Weilei Ma, Tiancheng Lei, Liangjian Liu, Guangying Ma, Hui Liao, Shiwei Ye, Jing Meng, Liang Song, Puxiang Lai, Yingjie Zhu, Kenneth K. Y. Wong, Hairong Zheng, Wei Zheng, Chengbo Liu
Full text
Exploring the relationship between neural activity and cerebral hemoglobin-oxygenation responses in freely behaving mice can advance our understanding of neurovascular coupling. Head-mounted microscopes enable neuroimaging in freely behaving mice; however, investigating neurovascular dynamics remains challenging because of a lack of hemodynamic information, especially blood oxygenation, or insufficient resolution. Here, we report a head-mounted microscope for neurovascular imaging that enables the simultaneous recording of neuronal burst firing and multiparametric hemodynamics such as vascular oxygen saturation at high spatiotemporal resolution. The 1.7-gram lightweight microscope integrates confocal fluorescence and photoacoustic microscopy, allowing recordings at 0.78 hertz with 1.5-micrometer lateral resolution across a field of view of 400 micrometers by 400 micrometers. We identified cell type–specific neurovascular responses to hypoxic challenges, observed active regulation of arterioles during sensory stimuli, and detected abnormal oxygen depletion and vasodilation preceding burst neuronal discharges in epileptic disorders. This technique provides valuable insights into neurovascular coupling and holds potential for studying the pathology of neurological brain diseases.
GPT-4o mini: Non-social science research article
SIP2 is the master transcription factor of Plasmodium merozoite formation
Tsubasa Nishi, Izumi Kaneko, Masao Yuda
Full text
Malaria, one of the most serious infectious diseases worldwide, is caused by the proliferation of Plasmodium parasites through repeated cycles of intraerythrocytic development. The parasite replicates via schizogony in host erythrocytes, producing multiple progeny merozoites that invade new erythrocytes. Although merozoite formation is the most crucial step in malaria pathogenesis, its molecular mechanism remains unclear. SIP2 is an AP2 transcription factor expressed during schizogony and is particularly conserved among erythrocyte-infecting apicomplexan parasites. Here, we reveal that SIP2 in Plasmodium berghei (PbSIP2) functions as the master transcription factor for merozoite formation. Conditional disruption of pbsip2 resulted in developmental arrest before merozoite formation and notable down-regulation of merozoite-related genes. ChIP-seq showed that PbSIP2 comprehensively activated merozoite-related genes by binding to previously reported cis-regulatory elements of merozoite invasion-related genes, including the bipartite motif (TGCAN 4–6 GTGCA). Collectively, our results indicate that SIP2 is a transcription factor that establishes erythrocyte infectivity and may have an evolutionary origin from the common ancestor of erythrocyte-infecting apicomplexan parasites.
GPT-4o mini: Non-social science research article
AMPK-dependent Parkin activation suppresses macrophage antigen presentation to promote tumor progression
Xinyu Wang, Yiyi Li, Yan Li, Xiumei Wang, Hongrui Song, Yingzhao Wang, Chunliu Huang, Chengzhou Mao, Lixiang Wang, Cheng Zhong, Di Yu, Zijin Xia, Yongyi Feng, Jingjing Duan, Yujia Liu, Juanjuan Ou, Congzhou Luo, Wenhao Mai, Hai Hong, Weibin Cai, Limin Zheng, Jean-François Trempe, Edward A. Fon, Jing Liao, Wei Yi, Jun Chen
Full text
The constrained cross-talk between myeloid cells and T cells in the tumor immune microenvironment (TIME) restricts cancer immunotherapy efficacy, whereas the underlying mechanism remains elusive. Parkin, an E3 ubiquitin ligase renowned for mitochondrial quality control, has emerged as a regulator of immune response. Here, we show that both systemic and macrophage-specific ablations of Parkin in mice lead to attenuated tumor progression and prolonged mouse survival. By single-cell RNA-seq and flow cytometry, we demonstrate that Parkin deficiency reshapes the TIME through activating both innate and adaptive immunities to control tumor progression and recurrence. Mechanistically, Parkin activation by AMP-activated protein kinase rather than PTEN-induced kinase 1 mediated major histocompatibility complex I down-regulation on macrophages via Autophagy related 5–dependent autophagy. Furthermore, Parkin deletion synergizes with immune checkpoint blockade treatment and Park2 −/− signature aids in predicting the prognosis of patients with solid tumor. Our findings uncover Parkin’s involvement in suppressing macrophage antigen presentation for coordinating the cross-talk between macrophages and T cells.
GPT-4o mini: Non-social science research article
Chiral ruthenium complex/Ph 2 P(2-furyl)–catalyzed asymmetric nucleophilic addition of aryl aldehyde hydrazones to simple ketones
Chenghao Zhu, Zihao Ye, Haining Wang, Da Ma, Zhiming Li, Chao-Jun Li, Junliang Zhang
Full text
An efficient synthesis of chiral tertiary alcohols through asymmetric nucleophilic addition reaction of aldehyde hydrazones to simple ketones (especially aryl/methyl ketones) has been well established. Aryl aldehydes could be used as latent benzyl carbanion equivalents via reductive polarity reversal. The key to the success of the asymmetric reaction was the combination of an achiral monophosphine ligand Ph 2 P(2-furyl) with a chiral diamine derivative, which enhanced the enantioselectivity and reactivity. Density functional theory calculations revealed the hydrogen bond interactions between the chiral diamine derivative, the achiral monophosphine ligand, and the base anion, which combined to induce the desired enantioselectivity. Moreover, further synthetic transformation of tertiary alcohols with high chirality transfer was also demonstrated.
GPT-4o mini: Non-social science research article
Stereoregular radical polymers enable selective spin transfer
Hyunki Yeo, Cole C. Sorensen, Hamas Tahir, Andrew Marquardt, Yun-Fang Yang, Nick Legaux, Brett M. Savoie, Frank A. Leibfarth, Bryan W. Boudouris
Full text
Spintronic devices are emerging as an approach to realize performance and energy efficiency beyond what is possible with traditional electronic devices. State-of-the-art metals and doped conjugated polymers used for spin manipulation suffer from fundamental performance and stability issues. We leveraged stereoselective cationic polymerization to design a polymer with a stable persistent radical in each repeat unit that enables the long-range order necessary for spin transport. This approach overcomes conventional requirements for doping in organic spin-pumping devices while showcasing high conductivity, long spin-diffusion lengths, and processability. Molecular-level alterations in polymer stereochemistry were critical for controlling spin-spin interactions and alignment. Stereoregular polymers with persistent neutral radicals represent a previously unidentified class of materials for manipulating spins over long distances for applications in next-generation information storage.
GPT-4o mini: Non-social science research article
Paramagnetic susceptibility measured by magnetic resonance imaging as an in vivo biomarker for iron pathology in epilepsy
Zhenghao Li, Qiangqiang Liu, Tongtong Xu, Ming Zhang, Li Li, Zhangpeng Chen, Yaohui Tang, Li Jiang, Yong Lu, Fuhua Yan, Yuyao Zhang, Jiwen Xu, Hongjiang Wei
Full text
Epilepsy, a neurological disorder marked by recurrent, unprovoked seizures, is often linked to dysregulated iron metabolism, resulting in iron overload and subsequent cellular dysfunction or death within epileptogenic regions. We proposed a specific, noninvasive technique using paramagnetic susceptibility imaging via magnetic resonance imaging to quantify in vivo brain iron levels, aiming to enhance our understanding of epilepsy pathology and improve diagnostic accuracy. Our imaging and histopathological studies demonstrated that paramagnetic susceptibility is a sensitive biomarker for iron quantification in epilepsy. This method effectively detects iron abnormality from various causes and highlights that iron alters within epileptogenic zones, indicating the presence of potentially salvageable tissue. Furthermore, iron accumulation was observed to disrupt cortical laminar structures in epileptogenic zones and was associated with the proliferation of central nervous system cells, particularly astrocytes. Paramagnetic susceptibility imaging provides previously unknown insights into epilepsy, offering potential applications in diagnostics, monitoring, and personalized treatment strategies.
GPT-4o mini: Non-social science research article
Distortion-free sampling of ultrabroadband terahertz electric fields by interfacial spin accumulation
Alexander L. Chekhov, Yannic Behovits, Julius J. F. Heitz, Maria-Andromachi Syskaki, Samridh Jaiswal, Oliver Gueckstock, Bruno R. Serrano, Amon Ruge, Jana Kredl, Martin Wolf, Markus MĂŒnzenberg, Gerhard Jakob, Mathias KlĂ€ui, Tom S. Seifert, Tobias Kampfrath
Full text
In spintronics, FM|HM stacks consisting of a ferromagnetic-metal (FM) and a heavy-metal (HM) layer are model systems for spin transport and spin-charge interconversion. To explore their potential as detectors for ultrabroadband terahertz electromagnetic pulses, we measure the transient optical birefringence the terahertz field induces. Notably, the signal component linear in the FM magnetization agrees excellently with the shape of the incident terahertz electric field at 1 to 13 terahertz and beyond. Analysis indicates that the birefringence arises from the terahertz-field–driven spin accumulation at the FM/HM interface through the spin Rashba-Edelstein effect (SREE). Because of spin-momentum locking, the SREE decays by electron momentum relaxation in <10 femtoseconds, substantially faster than a spin-Hall-effect–induced bulk spin accumulation. Our experiment demonstrates straightforward spintronic sampling of intense ultrabroadband terahertz fields with flat amplitude and phase response. Furthermore, it provides temporal signatures of the SREE and can be viewed as a versatile implementation of interface-specific terahertz time-domain spectroscopy.
GPT-4o mini: Non-social science research article
Imaging and simulation of surface plasmon polaritons on layered 2D MXenes
Janek Rieger, Atreyie Ghosh, Joseph L. Spellberg, Calvin Raab, Aishani Mohan, Prakriti P. Joshi, Sarah B. King
Full text
Two-dimensional (2D) transition metal carbides and nitrides, commonly known as MXenes, are a class of 2D materials with high free carrier densities, making them highly attractive candidates for plasmonic 2D materials. In this study, we use multiphoton photoemission electron microscopy ( n P-PEEM) to directly image the plasmonic near fields of multilayers of the prototypical MXene, Ti 3 C 2 T x , with mixed surface terminations (T x  = F, O, and OH). Photon-energy dependent n P-PEEM reveals a dispersive surface plasmon polariton between 1.4 and 1.9 electron volts on MXene flakes thicker than 30 nanometers and waveguide modes above 1.9 electron volts. Combining experiments with finite-difference time-domain simulations, we reveal the emergence of a visible surface plasmon polariton in MXenes, opening avenues for exploration of polaritonic phenomena in MXenes in the visible portion of the electromagnetic spectrum.
GPT-4o mini: Non-social science research article
NAT10 and N 4 -acetylcytidine restrain R-loop levels and related inflammatory responses
Turja K. Debnath, Nathan S. Abell, Yi-Ru Li, Sravan K. Devanathan, Enrique Navedo, Blerta Xhemalçe
Full text
N 4 -acetylcytidine (ac 4 C) is deposited on diverse RNAs by N -acetyltransferase 10 (NAT10), a protein with high biological relevance for aging and cancer. We performed a comprehensive survey of ac 4 C using metabolic labeling, sodium cyanoborohydride chemical treatment coupled to next-generation sequencing (NGS), and ac 4 C antibody–based cell and molecular biology techniques. Our analysis shows that NAT10-dependent ac 4 C-acetylation is robust in rRNA and specific tRNAs but low/spurious in mRNA. It also revealed an inflammatory signature and mutagenesis at transcriptionally active sites in NAT10-KO cells. This finding led us to explore the role of NAT10 in R-loops, which were recently linked to APOBEC3B-mediated mutagenesis. Our analysis showed that R-loops are ac 4 C-acetylated in a NAT10-dependent manner. Furthermore, NAT10 restrains the levels of R-loops at a subset of differentially expressed genes in a catalytic activity–dependent manner. Together with cellular biology data showing ac 4 C-modified RNA in endosomal structures, we propose that increased levels of ac 4 C-unmodified RNAs, likely derived from R-loops, in endosomal structures induce inflammatory responses.
GPT-4o mini: Non-social science research article
A dyad of human-specific NBPF14 and NOTCH2NLB orchestrates cortical progenitor abundance crucial for human neocortex expansion
Nesil EƟiyok, Neringa Liutikaite, Christiane Haffner, Jula Peters, Sabrina Heide, Christina Eugster Oegema, Wieland B. Huttner, Michael Heide
Full text
We determined the roles of two coevolved and coexpressed human-specific genes, NBPF14 and NOTCH2NLB , on the abundance of the cortical progenitors that underlie the evolutionary expansion of the neocortex, the seat of higher cognitive abilities in humans. Using automated microinjection into apical progenitors (APs) of embryonic mouse neocortex and electroporation of APs in chimpanzee cerebral organoids, we show that NBPF14 promotes the delamination of AP progeny, by promoting oblique cleavage plane orientation during AP division, leading to increased abundance of the key basal progenitor type, basal radial glia. In contrast, NOTCH2NLB promotes AP proliferation, leading to expansion of the AP pool. When expressed together, NBPF14 and NOTCH2NLB exert coordinated effects, resulting in expansion of basal progenitors while maintaining self-renewal of APs. Hence, these two human-specific genes orchestrate the behavior of APs, and the lineages of their progeny, in a manner essential for the evolutionary expansion of the human neocortex.
GPT-4o mini: Non-social science research article
Pregnancy and postpartum dynamics revealed by millions of lab tests
Alon Bar, Ron Moran, Netta Mendelsohn-Cohen, Yael Korem Kohanim, Avi Mayo, Yoel Toledano, Uri Alon
Full text
Pregnancy and delivery involve dynamic alterations in many physiological systems. However, the physiological dynamics during pregnancy and after delivery have not been systematically analyzed at high temporal resolution in a large human population. Here, we present the dynamics of 76 lab tests based on a cross-sectional analysis of 44 million measurements from over 300,000 pregnancies. We analyzed each test at weekly intervals from 20 weeks preconception to 80 weeks postpartum, providing detailed temporal profiles. About half of the tests take 3 months to a year to return to baseline postpartum, highlighting the physiological load of childbirth. The precision of the data revealed effects of preconception supplements, overshoots after delivery and intricate temporal responses to changes in blood volume and renal filtration rate. Pregnancy complications—gestational diabetes, preeclampsia, and postpartum hemorrhage—showed distinct dynamical changes. These results provide a comprehensive dynamic portrait of the systems physiology of pregnancy.
GPT-4o mini: Non-social science research article
Stealth and deception: Adaptive motion camouflage in hunting broadclub cuttlefish
Matteo Santon, Jolyon Troscianko, Charlie D. Heatubun, Martin J. How
Full text
Maintaining camouflage while moving is a challenge faced by many predators. Some exploit background motion to hide while hunting, and others may use coloration and behavior to generate motion noise that impairs detection or recognition. Here, we uncover a unique form of motion camouflage, showing that broadclub cuttlefish pass dark stripes downward across their head and arms to disguise their hunting maneuvers. This “passing-stripe” display reduces the probability of response to predatory expanding stimuli by prey crabs in a lab-based experiment, is modulated according to approach speed during a hunt, and generates a motion pattern that is different from that of looming predators. This form of motion camouflage likely functions by overwhelming the threatening motion of the approaching predator with nonthreatening downward motion generated by the rhythmic stripes.
GPT-4o mini: Non-social science research article
Systemic antitumor immune response of doped yttria nanoscintillators under low-dose x-ray irradiation
Onur Sahin, Yuri Mackeyev, Geraldine V. Vijay, Soumyabrata Roy, Ashokkumar Meiyazhagan, Yasmin Zahra, Okan Tezcan, Valeria Gonzalez, Belal Abousaida, Holden R. Wagner, Pearl Fernandes, Riaz Mowzoon-Mogharrabi, Bhanu P. Venkatesulu, Cheng-En Hsieh, Joseph B. K. Kim, Subhiksha Raghuram, Xiang Zhang, Kristen A. Miller, Guanhui Gao, Pankaj K. Singh, Sang Hyun Cho, Rao V. L. Papineni, Pulickel M. Ajayan, Sunil Krishnan
Full text
Inadequate light penetration in tissues restricts photodynamic therapy to treating only superficial tumors. To enable x-ray–excited photodynamic therapy (XPDT) that targets deep-seated tumors, we synthesized a nanoscintillator-photosensitizer complex containing 5% Eu-doped Y 2 O 3 fluorescing at 611 nanometers and decorated with SiO 2 containing the scintillation-coupled photosensitizer methylene blue and a polyethylene glycol coating [PEGylated Y 2 O 3 :Eu@SiO 2 -methylene blue (pYSM)]. When irradiated, pYSMs generate singlet oxygen species in vitro, causing cytotoxicity with hallmarks of immunogenic cell death (calreticulin translocation to the cell membrane). Intravenously administered pYSMs home passively to pancreatic tumor xenografts and, upon 10 gray irradiation, cause significant tumor regression ( P  < 0.01). On combining XPDT with anti-PD1 immunotherapy, a distant nonirradiated tumor also regresses via an increase in intratumoral activated CD8 + cytotoxic T cells. Collectively, we advance a systemically delivered XPDT strategy that mediates an antitumor effect in both irradiated and nonirradiated (abscopal) tumors when coupled with immunotherapy, converting an immunologically “cold” tumor to an immunologically “hot” tumor.
GPT-4o mini: Non-social science research article
Ultrabright difuranfluoreno-dithiophen polymers for enhanced afterglow imaging of atherosclerotic plaques
Zhe Li, Hui Cao, Youjuan Wang, Shiyi Liao, Xu Li, Baode Chen, Xiaosha Wang, Lihui Jiang, Yingping Zou, Xiao-bing Zhang, Guosheng Song
Full text
Cardiovascular diseases, including stroke driven by atherosclerosis, remain a leading global health concern. Current diagnostic imaging modalities such as magnetic resonance imaging fail to characterize oxidative stress within atherosclerotic plaques. Here, we introduce difuranfluoreno-dithiophen–based polymers designed for afterglow imaging, offering ultrabright luminescence, ultralow-power excitation (0.087 milliwatts per square centimeter), and ultrashort acquisition times (0.01 seconds). Through a molecular engineering strategy, we have optimized polymers for enhanced reactive oxygen species (ROS) generation capability, ROS capturing capability, and fluorescence quantum yield, resulting in an increase in afterglow intensity (~130-fold) compared to commonly used 2-methoxy-5-(2â€Č-ethylhexyloxy)-1,4-phenylenevinylene polymer (MEHPPV). Additionally, we have developed ratiometric afterglow nanoparticles doped with oxidative stress–responsive molecules, enabling imaging of oxidative stress markers in atherosclerotic plaque. This approach provides a tool for cardiovascular imaging and diagnostics, which is conducive to the auxiliary diagnosis and risk stratification of atherosclerosis.
GPT-4o mini: Non-social science research article
Parthenocissus -inspired soft climbing robots
Kecheng Qin, Wei Tang, Huaizhi Zong, Xinyu Guo, Huxiu Xu, Yiding Zhong, Yonghao Wang, Qincheng Sheng, Huayong Yang, Jun Zou
Full text
Climbing robots have attracted growing attention due to their mobility on vertical and nonplanar structural surfaces. However, the development of climbing robots capable of climbing on various complex surfaces remains elusive, especially on discontinuous surfaces. In nature, Parthenocissus climbs as it grows, having growing-climbing behaviors. Inspired by Parthenocissus , we propose a growing-climbing mechanism and report a soft climbing robot, which grows microstructured biofilms to enhance adhesion, similar to Parthenocissus growing suckers and adsorbing to the wall. The robot uses shape memory alloy contraction to achieve bending, similar to Parthenocissus using gelatinous fibers contraction to achieve hinge-like bending. In addition, to not damage the site, it can be fully contracted after completing tasks. The climbing robot can climb on various complex surfaces, especially discontinuous surfaces, verifying the effectiveness of Parthenocissus ’ growing-climbing mechanism. The growing-climbing mechanism is a universal climbing robot paradigm, opening a door for complex surface climbing robots.
GPT-4o mini: Non-social science research article
Astrobiological implications of the stability and reactivity of peptide nucleic acid (PNA) in concentrated sulfuric acid
Janusz J. Petkowski, Sara Seager, Maxwell D. Seager, William Bains, Nittert Marinus, Mael Poizat, Chad Plumet, Jim van Wiltenburg, Ton Visser, Martin Poelert
Full text
Recent renewed interest regarding the possibility of life in the Venusian clouds has led to new studies on organic chemistry in concentrated sulfuric acid. However, life requires complex genetic polymers for biological function. Therefore, finding suitable candidates for genetic polymers stable in concentrated sulfuric acid is a necessary first step to establish that biologically functional macromolecules can exist in this environment. We explore peptide nucleic acid (PNA) as a candidate for a genetic-like polymer in a hypothetical sulfuric acid biochemistry. PNA hexamers undergo between 0.4 and 28.6% degradation in 98% (w/w) sulfuric acid at ~25°C, over the span of 14 days, depending on the sequence, but undergo complete solvolysis above 80°C. Our work is the first key step toward the identification of a genetic-like polymer that is stable in this unique solvent and further establishes that concentrated sulfuric acid can sustain a diverse range of organic chemistry that might be the basis of a form of life different from Earth’s.
GPT-4o mini: Non-social science research article
Skin-interfaced multimodal sensing and tactile feedback system as enhanced human-machine interface for closed-loop drone control
Chunki Yiu, Yiming Liu, Wooyoung Park, Jian Li, Xingcan Huang, Kuanming Yao, Yuyu Gao, Guangyao Zhao, Hongwei Chu, Jingkun Zhou, Dengfeng Li, Hu Li, Binbin Zhang, Lung Chow, Ya Huang, Qingsong Xu, Xinge Yu
Full text
Unmanned aerial vehicles have undergone substantial development and market growth recently. With research focusing on improving control strategies for better user experience, feedback systems, which are vital for operator awareness of surroundings and flight status, remain underdeveloped. Current bulky manipulators also hinder accuracy and usability. Here, we present an enhanced human-machine interface based on skin-integrated multimodal sensing and feedback devices for closed-loop drone control. This system captures hand gestures for intuitive, rapid, and precise control. An integrated tactile actuator array translates the drone’s posture into two-dimensional tactile information, enhancing the operator’s perception of the flight situation. Integrated obstacle detection and neuromuscular electrical stimulation–based force feedback system enable collision avoidance and flight path correction. This closed-loop system combines intuitive controls and multimodal feedback to reduce training time and cognitive load while improving flight stability, environmental awareness, and the drone’s posture. The use of stretchable electronics also addresses wearability and bulkiness issues in traditional systems, advancing human-machine interface design.
GPT-4o mini: Non-social science research article
Histone modification–driven structural remodeling unleashes DNMT3B in DNA methylation
Chao-Cheng Cho, Hsun-Ho Huang, Bo-Chen Jiang, Wei-Zen Yang, Yi-Ning Chen, Hanna S. Yuan
Full text
The DNA methyltransferase 3B (DNMT3B) plays a vital role in shaping DNA methylation patterns during mammalian development. DNMT3B is intricately regulated by histone H3 modifications, yet the dynamic interplay between DNMT3B and histone modifications remains enigmatic. Here, we demonstrate that the PWWP (proline-tryptophan-tryptophan-proline) domain within DNMT3B exhibits remarkable dynamics that enhances the enzyme’s methyltransferase activity upon interactions with a modified histone H3 peptide (H3K4 me0 K36 me3 ). In the presence of H3K4 me0 K36 me3 , both the PWWP and ADD (ATRX-DNMT3-DNMT3L) domains transition from autoinhibitory to active conformations. In this active state, the PWWP domain most often aligns closely with the catalytic domain, allowing for simultaneous interactions with H3 and DNA to stimulate DNA methylation. The prostate cancer–associated DNMT3B R545C mutant is even more dynamic and susceptible to adopting the active conformation, resulting in aberrant DNA hypermethylation. Our study suggests the mechanism by which conformational rearrangements in DNMT3B are triggered by histone modifications, ultimately unleashing its activity in DNA methylation.
GPT-4o mini: Non-social science research article
Sub-wavelength optical lattice in 2D materials
Supratik Sarkar, Mahmoud Jalali Mehrabad, Daniel G. SuĂĄrez-Forero, Liuxin Gu, Christopher J. Flower, Lida Xu, Kenji Watanabe, Takashi Taniguchi, Suji Park, Houk Jang, You Zhou, Mohammad Hafezi
Full text
Recently, light-matter interaction has been vastly expanded as a control tool for inducing and enhancing many emergent nonequilibrium phenomena. However, conventional schemes for exploring such light-induced phenomena rely on uniform and diffraction-limited free-space optics, which limits the spatial resolution and the efficiency of light-matter interaction. Here, we overcome these challenges using metasurface plasmon polaritons (MPPs) to form a sub-wavelength optical lattice. Specifically, we report a “nonlocal” pump-probe scheme where MPPs are excited to induce a spatially modulated AC Stark shift for excitons in a monolayer of MoSe 2 , several microns away from the illumination spot. We identify nearly two orders of magnitude reduction for the required modulation power compared to the free-space optical illumination counterpart. Moreover, we demonstrate a broadening of the excitons’ linewidth as a robust signature of MPP-induced periodic sub-diffraction modulation. Our results will allow exploring power-efficient light-induced lattice phenomena below the diffraction limit in active chip-compatible MPP architectures.
GPT-4o mini: Non-social science research article
Physiology and climate change explain unusually high similarity across marine communities after end-Permian mass extinction
Jood A. Al Aswad, Justin L. Penn, Pedro M. Monarrez, Mohamad Bazzi, Curtis Deutsch, Jonathan L. Payne
Full text
Fossil assemblages exhibit a global depletion in taxonomic distinctiveness in the aftermath of the end-Permian mass extinction (~252 million years ago), but little is known about why. Here, we examine whether biotic homogenization can be explained by tropical survivors tracking an expansion of their preferred habitat, measured in terms of the ratio of environmental oxygen supply to metabolic demand. We compare spatial similarity in community composition among marine invertebrate fossils represented by bivalve and gastropod fossils with predictions from an ecophysiological model of habitat that diagnoses areas in the ocean that can sustain the aerobic requirements of marine invertebrates. Modeled biogeographic responses to climate change yield an increase in global similarity of community composition among surviving ecophysiotypes, consistent with patterns in the fossil record and arguing for a physiological control on earliest Triassic biogeography.
GPT-4o mini: Non-social science research article
Anthropogenic activity and climate change exacerbate the spread of pathogenic bacteria in the environment
Yu Geng, Ya Liu, Peng Li, Jingyu Sun, Yiru Jiang, Zhuo Pan, Yue-Zhong Li, Zheng Zhang
Full text
Climate change is profoundly affecting human health. Human pathogenic bacteria (HPB) infections mediated by the environment are considered a substantial cause of global health losses. However, the biogeography of HPB and their response to climate change remain largely unknown. Here, we constructed and analyzed a global atlas of potential HPB using 1,066,584 samples worldwide. HPB are widely present in the global environment, and their distribution follows a latitudinal diversity gradient. Climate and anthropogenic factors are identified as major drivers of the global distribution of HPB. Our predictions indicated that by the end of this century, the richness, abundance, and invasion risk of HPB will increase globally, with this upward trend becoming more pronounced as development sustainability declines. Therefore, the threat of environmentally mediated HPB infections to human health may be more severe in a world where anthropogenic activities are intensifying and the global climate is warming.
GPT-4o mini: Non-social science research article
Ultrafast energy transfer beyond the Förster approximation in organic photovoltaic blends with non-fullerene acceptors
Yanni Ouyang, Rui Wang, Xiaoyong Wang, Min Xiao, Chunfeng Zhang
Full text
Recent studies on organic photovoltaic (OPV) systems have highlighted the critical role of energy transfer in excited-state dynamics. This process has traditionally been explained through the model of long-range Förster resonance energy transfer (FRET). In this study, we demonstrate a donor-to-acceptor short-range energy transfer (SRET) mechanism in OPV blends with non-fullerene acceptors, extending beyond the Förster approximation. This SRET occurs as a two-step process mediated by interfacial excitations with mixed charge-transfer and local excitation features. We further validate this model through studies on planar heterojunctions, precisely controlling the thickness of interlayers. These findings underscore the short-range interactions in regulating the donor-to-acceptor energy transfer in OPV blends, suggesting that SRET should be considered alongside FRET and charge-transfer processes for device optimizations.
GPT-4o mini: Non-social science research article
Time-resolved tracking of cellulose biosynthesis and assembly during cell wall regeneration in live Arabidopsis protoplasts
Hyun Huh, Dharanidaran Jayachandran, Junhong Sun, Mohammad Irfan, Eric Lam, Shishir P. S. Chundawat, Sang-Hyuk Lee
Full text
Cellulose, the most abundant polysaccharide on earth composing plant cell walls, is synthesized by coordinated action of multiple enzymes in cellulose synthase complexes embedded within the plasma membrane. Multiple chains of cellulose fibrils form intertwined extracellular matrix networks. It remains largely unknown how newly synthesized cellulose is assembled into an intricate fibril network on cell surfaces. Here, we have established an in vivo time-resolved imaging platform to continuously visualize cellulose biosynthesis and fibril network assembly on Arabidopsis thaliana protoplast surfaces as the primary cell wall regenerates. Our observations provide the basis for a model of cellulose fibril network development in protoplasts driven by an interplay of multiscale dynamics that includes rapid diffusion and coalescence of nascent cellulose fibrils, processive elongation of single fibrils, and cellulose fibrillar network rearrangement during maturation. This study provides fresh insights into the dynamic and mechanistic aspects of cell wall synthesis at the single-cell level.
GPT-4o mini: Non-social science research article
Soft, stretchable conductive hydrogels for high-performance electronic implants
Md Saifur Rahman, Ahnsei Shon, Rose Joseph, Anton Pavlov, Alex Stefanov, Myeong Namkoong, Heng Guo, Dangnghi Bui, Reid Master, Archita Sharma, Jennifer Lee, Melissa Rivas, Ananya Elati, Yava Jones-Hall, Feng Zhao, Hangue Park, Michelle A. Hook, Limei Tian
Full text
Conductive hydrogels are emerging as promising materials for electronic implants owing to their favorable mechanical and electrical properties. Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels are particularly attractive, but their preparation often requires toxic additives. Here, we introduced a nutritive sweetener, d -sorbitol, as a nontoxic additive to create soft and stretchable PEDOT:PSS conductive hydrogels. These hydrogels exhibit mechanical properties comparable with biological tissues, reducing adverse immune responses. The hydrogels can be patterned on elastic substrates using a simple, low-cost micromolding technique to fabricate soft and stretchable implantable devices for electrical stimulation and recording. The hydrogel electrodes show much lower electrochemical impedance and higher charge storage and injection capacity compared to platinum electrodes. In addition, the properties of hydrogels and devices remain stable after long-term storage and exposure to extreme conditions. We demonstrate the use of soft hydrogel-based electronic devices for effective electrical stimulation and high-quality electrical recordings in live animal models.
GPT-4o mini: Non-social science research article
Climate warming and heatwaves accelerate global lake deoxygenation
Yibo Zhang, Kun Shi, R. Iestyn Woolway, Xiwen Wang, Yunlin Zhang
Full text
A widespread decline in dissolved oxygen (DO) has been observed in rivers, temperate lakes, and oceans, yet the impacts of climatic warming on global lake deoxygenation remain unclear. Here, we train data-driven models using climatic data, satellite images, and geographic factors to reconstruct surface DO and quantify the climatic contribution to DO variations in 15,535 lakes from 2003 to 2023. Our analysis indicates a continuous deoxygenation in 83% of the studied lakes. The mean deoxygenation rate in global lakes (−0.049 milligrams per liter per decade) is faster than that observed in the oceans and in rivers. By decreasing solubility, climatic warming contributes 55% of global lake deoxygenation. Meanwhile, heatwaves exert rapid influences on DO decline, resulting in a 7.7% deoxygenation compared to that observed under climatological mean temperatures. By the end of the century, global lake DO is projected to decrease by 0.41 milligrams per liter (4.3%) under SSP2-4.5 and 0.86 milligrams per liter (8.8%) under SSP5-8.5 scenarios.
GPT-4o mini: Non-social science research article
An in vivo screen identifies NAT10 as a master regulator of brain metastasis
Jocelyn F. Chen, Peng Xu, Wesley L. Cai, Huacui Chen, Emily Wingrove, Xiaojian Shi, Wenxue Li, Giulia Biancon, Meiling Zhang, Amer Balabaki, Ethan D. Krop, Elianna Asare, Yangyi Zhang, Mingzhu Yin, Toma Tebaldi, Jordan L. Meier, Thomas F. Westbrook, Stephanie Halene, Yansheng Liu, Hongying Shen, Don X. Nguyen, Qin Yan
Full text
Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis, the major cause of cancer-related deaths. Here, we conducted an in vivo screen for vulnerabilities of brain metastasis and identified N -acetyltransferase 10 (NAT10) as a driver of brain metastasis. Knockdown of NAT10 restrains cancer cell proliferation and migration in vitro and tumor growth and brain metastasis in vivo. The poorly characterized RNA helicase domain of NAT10 is critical for cell growth in vitro, while both RNA helicase and NAT domains are essential for primary tumor growth and brain metastasis in vivo. Mechanically, NAT10 promotes the expression of 3-phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1), two enzymes for serine biosynthesis implicated in brain metastasis. Silencing PHGDH or PSAT1 in metastatic breast cancer cells inhibits their growth in the serine/glycine-limited condition, phenocopying the effects of NAT10 depletion. These findings establish NAT10 as a key regulator of brain metastasis and nominate NAT10 as a target for treating metastasis.
GPT-4o mini: Non-social science research article
Frontal noradrenergic and cholinergic transients exhibit distinct spatiotemporal dynamics during competitive decision-making
Hongli Wang, Heather K. Ortega, Emma B. Kelly, Jonathan Indajang, Neil K. Savalia, Samira Glaeser-Khan, Jiesi Feng, Yulong Li, Alfred P. Kaye, Alex C. Kwan
Full text
Norepinephrine (NE) and acetylcholine (ACh) are crucial for learning and decision-making. In the cortex, NE and ACh are released transiently at specific sites along neuromodulatory axons, but how the spatiotemporal patterns of NE and ACh signaling link to behavioral events is unknown. Here, we use two-photon microscopy to visualize neuromodulatory signals in the premotor cortex (medial M2) as mice engage in a competitive matching pennies game. Spatially, NE signals are more segregated with choice and outcome encoded at distinct locations, whereas ACh signals can multiplex and reflect different behavioral correlates at the same site. Temporally, task-driven NE transients were more synchronized and peaked earlier than ACh transients. To test functional relevance, we stimulated neuromodulatory signals using optogenetics to find that NE, but not ACh, increases the animals’ propensity to explore alternate options. Together, the results reveal distinct subcellular spatiotemporal patterns of ACh and NE transients during decision-making in mice.
GPT-4o mini: Non-social science research article
Mycobacterium tuberculosis phagosome Ca 2+ leakage triggers multimembrane ATG8/LC3 lipidation to restrict damage in human macrophages
Di Chen, Antony Fearns, Maximiliano G. Gutierrez
Full text
The role of canonical autophagy in controlling Mycobacterium tuberculosis (Mtb), referred to as xenophagy, is understood to involve targeting Mtb to autophagosomes, which subsequently fuse with lysosomes for degradation. Here, we found that Ca 2+ leakage after Mtb phagosome damage in human macrophages is the signal that triggers autophagy-related protein 8/microtubule-associated proteins 1A/1B light chain 3 (ATG8/LC3) lipidation. Unexpectedly, ATG8/LC3 lipidation did not target Mtb to lysosomes, excluding the canonical xenophagy. Upon Mtb phagosome damage, the Ca 2+ leakage–dependent ATG8/LC3 lipidation occurred on multiple membranes instead of single or double membranes excluding the noncanonical autophagy pathways. Mechanistically, Ca 2+ leakage from the phagosome triggered the recruitment of the V-ATPase–ATG16L1 complex independently of FIP200, ATG13, and proton gradient disruption. Furthermore, the Ca 2+ leakage–dependent ATG8/LC3 lipidation limited Mtb phagosome damage and restricted Mtb replication. Together, we uncovered Ca 2+ leakage as the key signal that triggers ATG8/LC3 lipidation on multiple membranes to mitigate Mtb phagosome damage.
GPT-4o mini: Non-social science research article
Reelin marks cocaine-activated striatal neurons, promotes neuronal excitability, and regulates cocaine reward
Kasey L. Brida, Emily T. Jorgensen, Robert A. Phillips III, Catherine E. Newman, Jennifer J. Tuscher, Emily K. Morring, Morgan E. Zipperly, Lara Ianov, Kelsey D. Montgomery, Madhavi Tippani, Thomas M. Hyde, Kristen R. Maynard, Keri Martinowich, Jeremy J. Day
Full text
Drugs of abuse activate defined neuronal populations in reward structures such as the nucleus accumbens (NAc), which promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, mechanisms that dictate NAc neuronal recruitment remain unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling and targeted in situ detection to identify Reln (encoding the secreted glycoprotein, Reelin) as a marker of cocaine-activated neuronal populations within the rat NAc. A CRISPR interference approach enabling selective Reln knockdown in the adult NAc altered expression of calcium signaling genes, promoted a transcriptional trajectory consistent with loss of cocaine sensitivity, and decreased MSN excitability. Behaviorally, Reln knockdown prevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. These results identify Reelin as a critical mechanistic link between neuronal activation and cocaine-induced behavioral adaptations.
GPT-4o mini: Non-social science research article
Learning the rules of peptide self-assembly through data mining with large language models
Zhenze Yang, Sarah K. Yorke, Tuomas P. J. Knowles, Markus J. Buehler
Full text
Peptides are ubiquitous and important biomolecules that self-assemble into diverse structures. Although extensive research has explored the effects of chemical composition and exterior conditions on self-assembly, a systematic study consolidating these data to uncover global rules is lacking. In this work, we curate a peptide assembly database through a combination of manual processing by human experts and large language model–assisted literature mining. As a result, we collect over 1000 experimental data entries with information about peptide sequence, experimental conditions, and corresponding self-assembly phases. Using the data, machine learning models are developed, demonstrating excellent accuracy (>80%) in assembly phase classification. Moreover, we fine-tune a GPT model for peptide literature mining with the developed dataset, which markedly outperforms the pretrained model in extracting information from academic publications. This workflow can improve efficiency when exploring potential self-assembling peptide candidates, through guiding experimental work, while also deepening our understanding of the governing mechanisms.
GPT-4o mini: Non-social science research article
The emergence of human primordial germ cell–like cells in stem cell–derived gastruloids
Jitesh Neupane, Gabriele Lubatti, Theresa Gross-Thebing, Mayra Luisa Ruiz Tejada Segura, Richard Butler, Sargon Gross-Thebing, Sabine Dietmann, Antonio Scialdone, M. Azim Surani
Full text
Most advances in early human postimplantation development depend on animal studies and stem cell–based embryo models. Here, we present self-organized three-dimensional human gastruloids (hGs) derived from embryonic stem cells. The transcriptome profile of day 3 hGs aligned with Carnegie stage 7 human gastrula, with cell types and differentiation trajectories consistent with human gastrulation. Notably, we observed the emergence of nascent primordial germ cell–like cells (PGCLCs), but without exogenous bone morphogenetic protein (BMP) signaling, which is essential for the PGCLC fate. A mutation in the ISL1 gene affects amnion-like cells and leads to a loss of PGCLCs; the addition of exogenous BMP2 rescues the PGCLC fate, indicating that the amnion may provide endogenous BMP signaling. Our model of early human embryogenesis will enable further exploration of the germ line and other early human lineages.
GPT-4o mini: Non-social science research article
Programmable engineered bacteria as sustained-releasing antibody factory in situ for enhancing tumor immune checkpoint therapy
Xiao-Ting Xie, Meng Guan, Kai Cheng, Yong Li, Bin Zhang, Yi-Tong Zhou, Lin-Fang Tan, Peng-Shuo Dong, Si Chen, Bo Liu, Yuan-Di Zhao, Jin-Xuan Fan
Full text
Tumor immune checkpoint therapy (ICT) aims to block immune escape signals between tumor and immune cells. However, low delivery efficiency of immune checkpoint inhibitors (ICIs), narrow single-target approach, and reduced responsiveness notably hinder clinical development of ICT. Here, we developed a nanoliposome-bacteria hybrid system that acts as an antibody (Ab) factory, enabling precise tumor targeting and macrophage activation in hypoxic environments. We reprogrammed attenuated Escherichia coli MG1655 to synthesize CD47 antibodies (aCD47) in response to hypoxic tumor microenvironments while surface conjugating with redox-responsive macrophage colony-stimulating factor-loaded liposomes. This system leverages bacterial tropism to enhance macrophage infiltration and polarization. The low oxygen levels trigger in situ aCD47 expression, blocking the “do not eat me” signal and boosting macrophage antitumor activity. In addition, macrophage antigen presentation activates CD8+CD3+ T cells, amplifying systemic antitumor immunity. Analysis of the gut microbiome shows reduced pathogenicity and improved intestinal tolerance with increased probiotics.
GPT-4o mini: Non-social science research article
The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21
Suowen Xu, Zhenghong Liu, Tian Tian, Wenqi Zhao, Zhihua Wang, Monan Liu, Mengyun Xu, Fanshun Zhang, Zhidan Zhang, Meijie Chen, Yanjun Yin, Meiming Su, Wenxiang Fang, Wenhao Pan, Shiyong Liu, Min-dian Li, Peter J. Little, Danielle Kamato, Songyang Zhang, Dongdong Wang, Stefan Offermanns, John R. Speakman, Jianping Weng
Full text
Obesity is a debilitating global pandemic with a huge cost on health care due to it being a major underlying risk factor for several diseases. Therefore, there is an unmet medical need for pharmacological interventions to curb obesity. Here, we report that halofuginone, a Food and Drug Administration–approved anti-scleroderma and antiprotozoal drug, is a promising anti-obesity agent in preclinical mouse and pig models. Halofuginone suppressed food intake, increased energy expenditure, and resulted in weight loss in diet-induced obese mice while also alleviating insulin resistance and hepatic steatosis. Using molecular and pharmacological tools with transcriptomics, we identified that halofuginone increases fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) levels via activating integrated stress response. Using Gdf15 and Fgf21 knockout mice, we show that both hormones are necessary to elicit anti-obesity changes. Together, our study reports the beneficial metabolic effects of halofuginone and underscores its utility in treating obesity and its associated metabolic complications, which merits clinical assessment.
GPT-4o mini: Non-social science research article
Pathway-instructed therapeutic selection of ruxolitinib reduces neuroinflammation in fungal postinfectious inflammatory syndrome
Jessica C. Hargarten, Kenneth Ssebambulidde, Seher H. Anjum, Malcolm J. Vaughan, Jintao Xu, Anutosh Ganguly, Brittany Dulek, Francisco Otaizo-Carrasquero, Brian Song, Sijia Tao, Yoon-Dong Park, Terri L. Scott, Tracey-Ann Höltermann, Raymond F. Schinazi, Prashant Chittiboina, Bridgette Jeanne Billioux, Dima A. Hammoud, Michal A. Olszewski, Peter R. Williamson
Full text
Therapies to reduce neuroinflammation following resolution of acute central nervous system (CNS) infections are urgently needed, particularly for patients with non–HIV-associated cryptococcal meningoencephalitis complicated by a postinfectious inflammatory response syndrome (cPIIRS). To identify druggable targets in cPIIRS, patient cerebral spinal fluid samples underwent transcriptional analysis, revealing a Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway dominance in neuroinflammatory gene signatures. MurinecPIIRS models recapitulated this pathway predominance and treatment with the JAK inhibitor ruxolitinib, confirmed a mechanistic requirement for this pathway in disease pathology. Ruxolitinib treatment improved markers of neuronal damage, reduced activated T cell and myeloid cells, and improved weight. On the basis of these findings, we conducted a first-in-human ruxolitinib treatment of patients with cPIIRS (NCT00001352). Ruxolitinib treatment of six patients led to demonstrated tolerability, reductions in inflammatory biomarkers and activated immune cells, and improved brain imaging. These results advocate for pathway-instructed therapeutics in neuroinflammatory diseases and endorse JAK inhibitors in further clinical studies of cPIIRS.
GPT-4o mini: Non-social science research article
Skin regional specification and higher-order HoxC regulation
Shu-Man Hsieh Li, Ya-Chen Liang, Ting-Xin Jiang, Wen Chien Jea, Chih-Kuan Chen, Jiayi Lu, Daniel NĂșñez-LeĂłn, Zhou Yu, Yung-Chih Lai, Randall B. Widelitz, Leif Andersson, Ping Wu, Cheng-Ming Chuong
Full text
The integument plays a critical role in functional adaptation, with macro-regional specification forming structures like beaks, combs, feathers, and scales, while micro-regional specification modifies skin appendage shapes. However, the molecular mechanisms remain largely unknown. Craniofacial integument displays dramatic diversity, exemplified by the Polish chicken (PC) with a homeotic transformation of comb-to-crest feathers, caused by a 195–base pair (bp) duplication in HoxC10 intron. Micro-C analyses show that HoxC-containing topologically associating domain (TAD) is normally closed in the scalp but open in the dorsal and tail regions, allowing multiple long-distance contacts. In the PC scalp, the TAD is open, resulting in high HoxC expression. CRISPR-Cas9 deletion of the 195-bp duplication reduces crest feather formation, and HoxC misexpression alters feather shapes. The 195-bp sequence is found only in Archelosauria (crocodilians and birds) and not in mammals. These findings suggest that higher-order regulation of the HoxC cluster modulates gene expression, driving the evolution of adaptive integumentary appendages in birds.
GPT-4o mini: Non-social science research article
High-temperature surface state in Kondo insulator U 3 Bi 4 Ni 3
Christopher Broyles, Xiaohan Wan, Wenting Cheng, Dingsong Wu, Hengxin Tan, Qiaozhi Xu, Shannon L. Gould, Hasan Siddiquee, Leyan Xiao, Ryan Chen, Wanyue Lin, Yuchen Wu, Prakash Regmi, Yun Suk Eo, Jieyi Liu, Yulin Chen, Binghai Yan, Kai Sun, Sheng Ran
Full text
The resurgence of interest in Kondo insulators has been driven by two major mysteries: the presence of metallic surface states and the observation of quantum oscillations. To further explore these mysteries, it is crucial to investigate another similar system beyond the two existing ones, SmB 6 and YbB 12 . Here, we address this by reporting on a Kondo insulator, U 3 Bi 4 Ni 3 . Our transport measurements reveal that a surface state emerges below 250 kelvin and dominates transport properties below 150 kelvin, which is well above the temperature scale of SmB 6 and YbB 12 . At low temperatures, the surface conductivity is about one order of magnitude higher than the bulk. The robustness of the surface state indicates that it is inherently protected. The similarities and differences between U 3 Bi 4 Ni 3 and the other two Kondo insulators will provide valuable insights into the nature of metallic surface states in Kondo insulators and their interplay with strong electron correlations.
GPT-4o mini: Non-social science research article
Ultranarrow-linewidth wavelength-vortex metasurface holography
Weijia Meng, Johannes E. Fröch, Ke Cheng, Dapu Pi, Baoli Li, Arka Majumdar, Stefan A. Maier, Haoran Ren, Min Gu, Xinyuan Fang
Full text
Metasurface holograms harness multiple degrees of freedom of light to enhance information channel capacity. Traditionally, wavelength multiplexing holography with high-capacity information channel was only achievable through 3D volume holograms using Bragg diffraction. Here, we demonstrate ultranarrow-linewidth wavelength-vortex multiplexing holography in metasurface holograms. By applying elementary dispersion engineering, we develop a sparse k -vector–filtering aperture array in momentum space, enabling sharp wavelength selectivity combined with orbital angular momentum selectivity. Further leveraging transformer neural networks for the design of phase-only holograms, we showcase the reconstruction of up to 118 independent images from a single hologram, achieving a simulated ultranarrow linewidth of 2 nanometers within the visible range. We apply these developed metasurface holograms for holographic visual cryptography, attaining unprecedented security levels with an information rate over 2500 times higher than traditional methods. Our results open exciting avenues for the application of metasurface holograms in various fields, including 3D displays, holographic encryption, and optical artificial intelligence.
GPT-4o mini: Non-social science research article
Unveiling the complexity of Arnold’s tongues in a breathing-soliton laser
Xiuqi Wu, Junsong Peng, Bo Yuan, Sonia Boscolo, Christophe Finot, Heping Zeng
Full text
Synchronization occurs ubiquitously in nature and science. The synchronization regions generally broaden monotonically with the strength of the forcing, thereby featuring a tongue-like shape in parameter space, known as Arnold’s tongue. Such a shape is universal, prevailing in many diverse synchronized systems. Theoretical studies suggest that, under strong external forcing, the shape of the synchronization regions can change substantially and even holes can appear in the solid patterns. However, experimentally accessing these abnormal regimes is quite challenging mainly because many real-world systems displaying synchronization become fragile under strong forcing. Here, we are able to observe these intriguing regimes in a breathing-soliton laser. Two types of abnormal synchronization regions are unveiled, namely, a leaf- and a ray-like shape. High-resolution control of the loss allows holes to be revealed in the synchronization regions. Our work opens the possibility to study intriguing synchronization dynamics using a simple breathing-soliton laser as a test bed.
GPT-4o mini: Non-social science research article
Systematic high-throughput evaluation reveals FrCas9’s superior specificity and efficiency for therapeutic genome editing
Rui Tian, Xun Tian, Meiying Yang, Yuping Song, Tingting Zhao, Chaoyue Zhong, Wei Zhu, Ping Zhou, Zhiqiang Han, Zheng Hu
Full text
CRISPR-Cas9 systems have revolutionized genome editing, but the off-target effects of Cas9 limit its use in clinical applications. Here, we systematically evaluate FrCas9, a variant from Faecalibaculum rodentium , for cell and gene therapy (CGT) applications and compare its performance to SpCas9 and OpenCRISPR-1. OpenCRISPR-1 is a CRISPR system synthesized de novo using large language models (LLMs) but has not yet undergone systematic characterization. Using AID-seq, Amplicon sequencing, and GUIDE-seq, we assessed the on-target activity and off-target profiles of these systems across multiple genomic loci. FrCas9 demonstrated higher on-target efficiency and substantially fewer off-target effects than SpCas9 and OpenCRISPR-1. Furthermore, TREX2 fusion with FrCas9 reduced large deletions and translocations, enhancing genomic stability. Through screening of 1903 sgRNAs targeting 21 CGT-relevant genes using sequential AID-seq, Amplicon sequencing, and GUIDE-seq analysis, we identified optimal sgRNAs for each gene. Our high-throughput screening platform highlights FrCas9, particularly in its TREX2-fused form, as a highly specific and efficient tool for precise therapeutic genome editing.
GPT-4o mini: Non-social science research article
HMCES corrupts replication fork stability during base excision repair in homologous recombination–deficient cells
María José Peña-Gómez, Yaiza Rodríguez-Martín, Marta del Rio Oliva, Yodhara Wijesekara Hanthi, Sara Berrada, Raimundo Freire, Jean Yves Masson, José Carlos Reyes, Vincenzo Costanzo, Ivån V. Rosado
Full text
Apurinic/apyrimidinic (AP) sites and single-strand breaks arising from base excision repair (BER) during the misincorporation of damaged nucleobases may hinder replication fork stability in homologous recombination–deficient (HRD) cells. At templated AP sites, cross-links between the DNA and 5-hydroxymethylcytosine binding, embryonic stem cell–specific (HMCES) regulate replication fork speed, avoiding cytotoxic double-strand breaks. While the role of HMCES at the template DNA strand is well studied, its effects on nascent DNA are not. We provide evidence that HMCES–DNA-protein cross-links (DPCs) are detrimental to the BER-mediated removal of 5-hydroxymethyl-2â€Č-deoxycytidine (5hmdC)–derived 5-hydroxymethyl-2â€Č-deoxyuridine from replication forks. HRD cells have heightened HMCES-DPCs, which increase further upon 5hmdC exposure, suggesting that HMCES binds both spontaneous and 5hmdC-induced AP sites. HMCES depletion substantially suppresses 5hmdC-mediated replication fork defects, chromosomal aberrations, and cell death in HRD cells. This reveals that HMCES-DPCs are a source of BER-initiated single-stranded DNA gaps, which indicates that endogenous DPCs contribute to genomic instability in HRD tumors.
GPT-4o mini: Non-social science research article
Phosphorylation at serine-260 of Toc33 is essential for chloroplast biogenesis
Yuan-Chi Chien, Gyeong Mee Yoon
Full text
Chloroplast biogenesis, essential for photosynthesis, depends on the import of nuclear-encoded proteins through the translocon at the outer envelope of chloroplasts (TOC) complexes. Despite its importance, the mechanisms regulating this process remain largely elusive. We identify serine-260 (S260) as a critical phosphorylation site in Toc33, a core TOC component. This phosphorylation stabilizes Toc33 by preventing its ubiquitination and degradation. Constitutive triple response 1 (CTR1), a negative regulator of ethylene signaling, and its paralog RAF-like kinase are involved in phosphorylating Toc33. Disruption of Toc33 phosphorylation impairs its stability and photosynthetic protein import, consequently affecting chloroplast structural integrity and biogenesis. Our findings underscore the essential role of TOC phosphorylation in chloroplast biogenesis and reveal an unexpected regulatory network involving RAF-like kinases in organelle development.
GPT-4o mini: Non-social science research article
A millisecond integrated quantum memory for photonic qubits
Yu-Ping Liu, Zhong-Wen Ou, Tian-Xiang Zhu, Ming-Xu Su, Chao Liu, Yong-Jian Han, Zong-Quan Zhou, Chuan-Feng Li, Guang-Can Guo
Full text
Quantum memories for light are essential building blocks for quantum repeaters and quantum networks. Integrated operations of quantum memories could enable scalable application with low-power consumption. However, the photonic quantum storage lifetime in integrated devices has so far been limited to tens of microseconds, falling short of the requirements for practical applications. Here, we demonstrate quantum storage of photonic qubits for 1.021 milliseconds based on a laser-written optical waveguide fabricated in a 151 Eu 3+ :Y 2 SiO 5 crystal. Spin dephasing of 151 Eu 3+ is mitigated through dynamical decoupling applied via on-chip electric waveguides, and we obtain a storage efficiency of 12.0 ± 0.5% at 1.021 milliseconds, which is a demonstration of integrated quantum memories that outperforms the efficiency of a simple fiber delay line. Such long-lived waveguide-based quantum memory could support applications in quantum repeaters, and further combination with critical magnetic fields could enable potential application as transportable quantum memories.
GPT-4o mini: Non-social science research article
Making continental crust on water-bearing terrestrial planets
Justine Bernadet, Anastassia Y. Borisova, Martin Guitreau, Oleg G. Safonov, Paul Asimow, Anne Nédélec, Wendy A. Bohrson, Svetlana A. Kosova, Philippe de Parseval
Full text
The debate about early Earth differentiation focuses on the processes responsible for the formation of protocrust(s) and continental crust of felsic (SiO 2  ≄ 55 weight %) composition. One aspect of this debate is how Hadean zircons fit into an ultramafic environment. On the basis of experiments, thermodynamic modeling, and elemental partitioning, we show that felsic melts could have been generated by shallow interaction between primordial serpentinized peridotite and basaltic magmas on Earth and Mars. On the basis of the hafnium isotopic evolution of Hadean detrital zircons worldwide, we infer that these interactions allowed for the formation of extensive Hadean felsic crust (4.4 to 4.5 billion years ago), which, in turn, would account for up to 50% of the present continental crustal mass. A similar process may have occurred on Mars. The serpentinized protocrust had a dual role in the primitive planetary environment: to provide ingredients for the continental crust and to enable life to emerge on water-bearing terrestrial planets.
GPT-4o mini: Non-social science research article
Activity-dependent regulation of Cdc42 by Ephexin5 drives synapse growth and stabilization
Samuel Petshow, Azariah Coblentz, Andrew M. Hamilton, Dipannita Sarkar, Margarita Anisimova, Juan C. Flores, Karen Zito
Full text
Synaptic Rho guanosine triphosphatase (GTPase) guanine nucleotide exchange factors (RhoGEFs) play vital roles in regulating the activity-dependent neuronal plasticity that is critical for learning. Ephexin5, a RhoGEF implicated in the etiology of Alzheimer’s disease and Angelman syndrome, was originally reported in neurons as a RhoA-specific GEF that negatively regulates spine synapse density. Here, we show that Ephexin5 activates both RhoA and Cdc42 in the brain. Furthermore, using live imaging of GTPase biosensors, we demonstrate that Ephexin5 regulates activity-dependent Cdc42, but not RhoA, signaling at single synapses. The selectivity of Ephexin5 for Cdc42 activation is regulated by tyrosine phosphorylation, which is regulated by neuronal activity. Last, in contrast to Ephexin5’s role in negatively regulating synapse density, we show that, downstream of neuronal activity, Ephexin5 positively regulates synaptic growth and stabilization. Our results support a model in which plasticity-inducing neuronal activity regulates Ephexin5 tyrosine phosphorylation, driving Ephexin5-mediated activation of Cdc42 and the spine structural growth and stabilization vital for learning.
GPT-4o mini: Non-social science research article
Catalyst-controlled regiodivergence and stereodivergence in formal cross-[4+2] cycloadditions: The unique effect of bismuth(III)
Qiumeng Hou, Chenxi Cai, Shuai-Jiang Liu, Wei Huang, Cheng Peng, Gu Zhan, Bo Han
Full text
The [4+2] cycloaddition is crucial for constructing six-membered rings in pharmaceuticals and natural products. Cross-[4+2] cycloadditions offer greater product diversity than traditional diene-dienophile reactions due to multiple possible pathways. However, precise control over regio- and stereoselectivity for various isomers remains a great challenge. This study reports catalyst-controlled regiodivergent formal cross-cycloadditions of acyclic dienes and enones, significantly enhancing access to diverse pyrazole-fused spirooxindoles. Chiral phosphoric acid (CPA) catalysis enables endoselective [4+2] cycloadditions, while Bi(III) with a CPA ligand yields [2+4] products with high regio- and stereoselectivity. A Claisen rearrangement of the [2+4] adduct produces the exo-selective [4+2] product, further increasing stereochemical diversity and enabling the synthesis of six regio- and stereo-isomers from a single substrate set. DFT calculations reveal that Bi(III) reverses regioselectivity by repositioning reactants in the CPA pocket and stabilizing the enone oxygen’s negative charge. In addition, product 3as demonstrates therapeutic potential against triple-negative breast cancer, with an IC 50 of 8.5 ÎŒM in MDA-MB-453 cells.
GPT-4o mini: Non-social science research article
Nanoelectronics-enabled reservoir computing hardware for real-time robotic controls
Mingze Chen, Xiaoqiu An, Seung Jun Ki, Xirong Liu, Nihal Sekhon, Artyom Boyarov, Anushka Acharya, Justin Tawil, Maxwell Bederman, Xiaogan Liang
Full text
Traditional robotic vehicle control algorithms, implemented on digital devices with firmware, result in high power consumption and system complexity. Advanced control systems based on different device physics are essential for the advancement of sophisticated robotic vehicles and miniature mobile robots. Here, we present a nanoelectronics-enabled analog control system mimicking conventional controllers’ dynamic responses for real-time robotic controls, substantially reducing training cost, power consumption, and footprint. This system uses a reservoir computing network with interconnected memristive channels made from layered semiconductors. The network’s nonlinear switching and short-term memory characteristics effectively map input sensory signals to high-dimensional data spaces, enabling the generation of motor control signals with a simply trained readout layer. This approach minimizes software and analog-to-digital conversions, enhancing energy and resource efficiency. We demonstrate this system with two control tasks: rover target tracking and drone lever balancing, achieving similar performance to traditional controllers with ~10-microwatt power consumption. This work paves the way for ultralow-power edge computing in miniature robotic systems.
GPT-4o mini: Non-social science research article
The expression order determines the pioneer functions of NGN3 and NEUROD1 in pancreatic endocrine differentiation
Liu Yang, Xin-Xin Yu, Xin Wang, Chen-Tao Jin, Cheng-Ran Xu
Full text
Pioneer transcription factors (TFs) initiate chromatin remodeling, which is crucial for gene regulation and cell differentiation. In this study, we investigated how the sequential expression of neurogenin 3 (NGN3) and NEUROD1 affects their pioneering functions during pancreatic endocrine differentiation. Using a genetically engineered mouse model, we mapped NGN3-binding sites, confirming the pivotal role of this molecule in regulating chromatin accessibility. The pioneering function of NGN3 involves dose tolerance, and low doses are sufficient. Although NEUROD1 generally acts as a conventional TF, it can assume a pioneering role in the absence of NGN3. The sequential expression of NeuroD1 and Ngn3 predominantly drives α cell generation, which may explain the inefficient ÎČ cell induction observed in vitro. Our findings demonstrate that pioneer activity is dynamically shaped by temporal TF expression and inter-TF interactions, providing insights into transcriptional regulation and its implications for disease mechanisms and therapeutic targeting and enhancing in vitro differentiation strategies.
GPT-4o mini: Non-social science research article
Monitoring microvascular changes over time with a repositionable 3D ultrasonic capacitive micromachined row-column sensor
Cyprien Blanquart, Léa Davenet, Julien Claisse, Mallorie Giroud, Audren Boulmé, Edgard Jeanne, Mickaël Tanter, Mafalda Correia, Thomas Deffieux
Full text
eHealth devices, including smartwatches and smart scales, have the potential to transform health care by enabling continuous, real-time monitoring of vital signs over extended periods. Existing technologies, however, lack comprehensive monitoring of the microvascular network, which is linked to conditions such as diabetes, hypertension, and small vessel diseases. This study introduces an ultrasound approach using a capacitive micromachined ultrasound transducer row-column array for continuous, ultrasensitive three-dimensional (3D) Doppler imaging of microvascular changes such as hemodynamic variations or vascular remodeling. In vitro tests and in vivo studies with healthy volunteers demonstrated the sensor’s ability to image the 3D microvascular network at high resolution over different timescales with automatic registration and to detect microvascular changes with high sensitivity. Integrating this technology into wearable devices could, one day, enhance understanding, monitoring, and possibly early detection of microvascular-related health conditions.
GPT-4o mini: Non-social science research article
Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models
Rita Ferla, Eugenio Pugni, Mariangela Lupo, Paola Tiberi, Federica Fioretto, Andrea Perota, Roberto Duchi, Irina Lagutina, Carlo Gesualdo, Settimio Rossi, Domenico Ventrella, Alberto Elmi, Benjamin McClinton, Carmel Toomes, Tongzhou Xu, Robert S. Molday, Enrico M. Surace, Francesca Simonelli, Maria L. Bacci, Cesare Galli, Muhammad A. Memon, Naveed Shams, Alberto Auricchio, Ivana Trapani
Full text
Retinal gene therapy using dual adeno-associated viral (AAV) intein vectors can be applied to genetic forms of blindness caused by mutations in genes with coding sequences that exceed single AAV cargo capacity, such as Stargardt disease (STGD1), the most common inherited macular dystrophy. In view of clinical translation of dual AAV intein vectors, here we set to evaluate both the efficiency and safety of their subretinal administration in relevant large animal models. Accordingly, we have developed the first pig model of STGD1, which we found to accumulate lipofuscin similarly to patients. This accumulation is significantly reduced upon subretinal administration of dual AAV intein vectors whose safety and pharmacodynamics we then tested in nonhuman primates, which showed modest and reversible inflammation as well as high levels of photoreceptor transduction. This bodes well for further clinical translation of dual AAV intein vectors in patients with STGD1 as well as for other blinding diseases that require the delivery of large genes.
GPT-4o mini: Non-social science research article
Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD + synthesis via enterohepatic circulation
Keisuke Yaku, Sailesh Palikhe, Tooba Iqbal, Faisal Hayat, Yoshiyuki Watanabe, Shiho Fujisaka, Hironori Izumi, Tomoyuki Yoshida, Mariam Karim, Hitoshi Uchida, Allah Nawaz, Kazuyuki Tobe, Hisashi Mori, Marie E. Migaud, Takashi Nakagawa
Full text
Decreased nicotinamide adenine dinucleotide (oxidized form) (NAD + ) levels are reportedly associated with several aging-related disorders. Thus, supplementation with NAD + precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), exhibits beneficial effects against these disorders. However, the in vivo metabolic pathways of NMN and NR remain to be elucidated. In this study, we comprehensively analyzed the fate of orally and intravenously administered NMN and NR in mice using NAD + metabolomics. We found that only a small portion of orally administered NMN and NR was directly absorbed from the small intestine and that most of them underwent gut microbiota–mediated deamidation and conversion to nicotinic acid (NA). Moreover, intravenously administered NMN and NR were rapidly degraded into nicotinamide and secreted to bile followed by deamidation to NA by gut microbiota. Thus, enterohepatic circulated NA is preferentially used in the liver. These findings showed that NMN and NR are indirectly converted to NAD + via unexpected metabolic pathways.
GPT-4o mini: Non-social science research article
Self-powered electrotactile textile haptic glove for enhanced human-machine interface
Guoqiang Xu, Haoyu Wang, Guangyao Zhao, Jingjing Fu, Kuanming Yao, Shengxin Jia, Rui Shi, Xingcan Huang, Pengcheng Wu, Jiyu Li, Binbin Zhang, Chun Ki Yiu, Zhihao Zhou, Chaojie Chen, Xinyuan Li, Zhengchun Peng, Yunlong Zi, Zijian Zheng, Xinge Yu
Full text
Human-machine interface (HMI) plays an important role in various fields, where haptic technologies provide crucial tactile feedback that greatly enhances user experience, especially in virtual reality/augmented reality, prosthetic control, and therapeutic applications. Through tactile feedback, users can interact with devices in a more realistic way, thereby improving the overall effectiveness of the experience. However, existing haptic devices are often bulky due to cumbersome instruments and power modules, limiting comfort and portability. Here, we introduce a concept of wearable haptic technology: a thin, soft, self-powered electrotactile textile haptic (SPETH) glove that uses the triboelectric effect and gas breakdown discharge for localized electrical stimulation. Daily hand movements generate sufficient mechanical energy to power the SPETH glove. Its features—softness, lightweight, self-sustainability, portability, and affordability—enable it to provide tactile feedback anytime and anywhere without external equipment. This makes the SPETH glove an enhanced, battery-free HMI suitable for a wide range of applications.
GPT-4o mini: Non-social science research article
Eliminating nonuniform geometric effects for long-term stable electrochemical extraction of high-purity titanium
Zhiyuan Li, Shuqiang Jiao, Jun Zhu, Shijie Li, Zhaoliang Qu, Xiaodong Chen, Qi Wang, Shanyan Huang, Hao-Sen Chen, Wei-Li Song, Yingjun Liu, Dongbai Sun, Hongmin Zhu, Daining Fang
Full text
Electrorefining of low-grade titanium is one of the strategies for achieving high-purity titanium. However, the presence of nonuniform geometric effects would be induced to impact the nonuniform geometric distribution of overpotential, leading to impurity dissolution and nonuniform Ti deposition. Here, in situ high-temperature characterizations on the molten salt electrorefining process are applied to establish an anodic dissolution principle for quantitatively evaluating nonuniform geometric effects of electrode. For eliminating the nonuniform geometric effects, coaxial anode-cathode configurations are designed to promote the nonuniform anodic dissolution and nonuniform cathodic deposition. Consequently, the geometric uniformity of titanium products on the cathodes is substantially enhanced, and thus, long-term stable electrorefining process (~12 hours, ~330% increment compared to the electrode of reference configuration) and highly purified titanium products (99.2%) are achieved.
GPT-4o mini: Non-social science research article
Purely organic room-temperature phosphorescence sensitizers for highly efficient hyperfluorescence OLEDs
Jiajie Zeng, Shaoxin Song, Yan Fu, Xiaoluo Peng, Ben Zhong Tang, Zujin Zhao
Full text
Multiresonance thermally activated delayed fluorescence (MR-TADF) emitters are promising candidates for organic light-emitting diodes (OLEDs) with high color quality. However, in most cases, noble metal–containing phosphors are required as sensitizers for MR-TADF emitters to improve their electroluminescence (EL) performances, which may lead to high cost and environmental pollution. Herein, an efficient purely organic room-temperature phosphorescence (RTP) material, 3,2-PIC-TXT, with fast phosphorescence radiation is developed. It not only exhibits impressive EL performances as an emitter with an outstanding external quantum efficiency (EQE) of 33.2%, higher than that of Ir(ppy) 3 (25.2%), but also functions remarkably as a sensitizer for green MR-TADF emitters (BN2, tCzphB-Ph, and tCzphB-Fl). The hyperfluorescence OLEDs using 3,2-PIC-TXT as a sensitizer provide ultrahigh EQEs of 40.9 to 43.8%, superior to those based on an Ir(ppy) 3 sensitizer (37.0 to 38.0%), along with superb color purity and excellent operational stability. These OLEDs are the best devices based on RTP materials reported so far.
GPT-4o mini: Non-social science research article
Lensless imaging with a programmable Fresnel zone aperture
Xu Zhang, Bowen Wang, Sheng Li, Kunyao Liang, Haitao Guan, Qian Chen, Chao Zuo
Full text
Optical imaging has long been dominated by traditional lens-based systems that, despite their success, are inherently limited by size, weight, and cost. Lensless imaging seeks to overcome these limitations by replacing lenses with thinner, lighter, and cheaper optical modulators and reconstructing images computationally, while facing trade-offs in image quality, artifacts, and flexibility inherent in traditional static modulation. Here, we propose a lensless imaging method with programmable Fresnel zone aperture (FZA), termed LIP. With a commercial liquid crystal display, we designed an integrated LIP module and demonstrated its capability of high-quality artifact-free reconstruction through dynamic modulation and offset-FZA parallel merging. Compared to static-modulation approaches, LIP achieves a 2.5× resolution enhancement and a 3 decibels improvement in signal-to-noise ratio in “static mode” while maintaining an interaction frame rate of 15 frames per second in “dynamic mode.” Experimental results demonstrate LIP’s potential as a miniaturized platform for versatile advanced imaging tasks like virtual reality and human-computer interaction.
GPT-4o mini: Non-social science research article
A synthetic genomics-based African swine fever virus engineering platform
Walter Fuchs, Nacyra Assad-Garcia, Hussein M. Abkallo, Yong Xue, Lauren M. Oldfield, Nadia Fedorova, Alexandra HĂŒbner, Tonny Kabuuka, Katrin Pannhorst, Dirk Höper, Vishvanath Nene, Norberto Gonzalez-Juarbe, Lucilla Steinaa, Sanjay Vashee
Full text
African swine fever (ASF) is a deadly viral disease in domestic pigs that has a large global economic impact for the swine industry. It is present in Africa, Europe, Asia, and in the Caribbean island of Hispaniola. There are no effective treatments or broadly licensed vaccines to prevent disease. Efforts to counteract ASF have been hampered because of the lack of convenient tools to engineer its etiological agent, ASF virus (ASFV), largely due to its large noninfectious genome. Here, we report the use of synthetic genomics methodology to develop a reverse genetics system for ASFV using a CRISPR-Cas9–inhibited self-helper virus to reconstitute live recombinant ASFV from synthetic genomes to rapidly generate a variety of combinatorial mutants of ASFV. The method will substantially facilitate the development of therapeutics or subunit and live-attenuated vaccines for ASF. This synthetic genomics-based approach has wide-ranging impact because it can be applied to rapidly develop reverse genetics tools for emerging viruses with noninfectious genomes.
GPT-4o mini: Non-social science research article
A memristor-based unified PUF and TRNG chip with a concealable ability for advanced edge security
Xueqi Li, Bohan Lin, Bin Gao, Yuyao Lu, Siyao Yang, Zhiqiang Su, Ting-Ying Shen, Jianshi Tang, He Qian, Huaqiang Wu
Full text
Security primitives ensure Internet of Things (IoT) security by generating stable keys from physically unclonable functions (PUFs) and unpredictable bitstreams from true random number generators (TRNGs). Considering the restricted resources on IoT motes, a promising design trend is to unify PUF and TRNG by sharing the same entropy source and multiplexing entropy extractor. Here, we report a unified PUF and TRNG chip based on a 28-nanometer embedded memristor with concealable ability. We use the memristor intrinsic FORMING condition variation and read current variation as entropy sources and design a compact on-chip entropy extractor that achieves a high throughput of 41.7 megabits per second with minimal area overhead of 0.291 MF 2 . To prevent PUF data leakage, we developed a concealment method, protecting data when idle and enabling recovery upon demand. Comprehensive testing shows the chip has excellent performance in randomness, reliability, lifetime, and stability, achieving a 3.82-fold throughput improvement over complementary metal-oxide semiconductor–based designs in authentication tasks.
Harnessing huge data from pregnancy natural experiments
Michelle Oyen
Full text
Vast, cross-sectional, and open datasets are critical for understanding complex pregnancy physiology and women’s health more generally while serving as a resource for model development.

Socio-Economic Review

The transition to the knowledge economy in advanced capitalist democracies: a new index for comparative research
Sebastian Diessner, Niccolo Durazzi, Federico Filetti, David Hope, Hanna Kleider, Simone Tonelli
Full text
This article sets out to develop a new index capturing advanced capitalist democracies’ transition to the knowledge economy. Reviewing how the notion has evolved in the literature, the article proposes a definition of the knowledge economy based upon two key elements—technology and (high) skills. These are operationalized in six indicators and combined through Bayesian latent variable analysis to produce a new Knowledge Economy Index, covering twenty-two countries from 1995 to 2019. A descriptive exploration of the index provides important insights for the emerging body of work on the knowledge economy in comparative political economy. The index is the first to provide a comprehensive measure of the knowledge economy that accounts for both technology and skills across space and time. As such, it paves the way for future research examining the causes and consequences of the transition to the knowledge economy in advanced capitalist democracies.
Economic costs of democratic backsliding: how does democratic backsliding affect sovereign bond ratings?
Seong Hun Yoo
Full text
Gradual declines of democratic regimes characterize the contemporary political landscape. In response to this trend, a burgeoning body of literature has explored the consequences of democratic backsliding in various sectors. This study focuses on the effect of democratic backsliding on financial markets, specifically sovereign bond ratings issued by credit rating agencies. I argue that backsliding countries are more likely to face downgrades in their bond ratings. This is because the erosion of democratic institutions undermines the “democratic advantage”—characterized by electoral accountability, institutional checks and balances, and pro-economic policies—thereby increasing the likelihood of default. Using up to seventy-nine democratic countries from 1995 to 2018, I find robust support for the adverse effects of backsliding on bond ratings. That is, backsliding countries have significantly poorer credit ratings than democratic countries that do not undergo backsliding. These findings deepen our understanding of how democratic backsliding affects the international political economy, emphasizing that democratic practices are crucial for sustaining financial stability.