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Integer partitions detect the primes Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 William Craig, Jan-Willem van Ittersum, Ken Ono
We show that integer partitions, the fundamental building blocks in additive number theory, detect prime numbers in an unexpected way. Answering a question of Schneider, we show that the primes are the solutions to special equations in partition functions. For example, an integer n ≥ 2 is prime if and only if ( 3 n 3 − 13 n 2 + 18 n − 8 ) M 1 ( n ) + ( 12 n 2 − 120 n + 212 ) M 2 ( n ) − 960 M 3 ( n
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The battle of the sexes in humans is highly polygenic Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Jared M. Cole, Carly B. Scott, Mackenzie M. Johnson, Peter R. Golightly, Jedidiah Carlson, Matthew J. Ming, Arbel Harpak, Mark Kirkpatrick
Sex-differential selection (SDS), which occurs when the fitness effects of alleles differ between males and females, can have profound impacts on the maintenance of genetic variation, disease risk, and other key aspects of natural populations. Because the sexes mix their autosomal genomes each generation, quantifying SDS is not possible using conventional population genetic approaches. Here, we introduce
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Alternating access of a bacterial homolog of neurotransmitter: sodium symporters determined from AlphaFold2 ensembles and DEER spectroscopy. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Alexandra C Schwartz,Richard A Stein,Eva Gil-Iturbe,Matthias Quick,Hassane S Mchaourab
Neurotransmitter:sodium symporters (NSSs) play critical roles in neural signaling by regulating neurotransmitter uptake into cells powered by sodium electrochemical gradients. Bacterial NSSs orthologs, including MhsT from Bacillus halodurans, have emerged as model systems to understand the structural motifs of alternating access in NSSs and the extent of conservation of these motifs across the family
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QnAs with Scott E. Heatwole and Robert F. Pfaff. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Matthew Hardcastle
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Current usage of sounding rockets to study the upper atmosphere. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Scott E Heatwole
Sounding rockets have played and continue to play a key role in the modeling of the upper atmosphere and predicting weather. Goddard's insight into the usefulness of rockets for this application came at a time when measurements had not been made above the troposphere. Present-day developments in sounding rockets have allowed more elaborate experiments to make measurements with multiple rockets and
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Beyond Neyman–Pearson: E-values enable hypothesis testing with a data-driven alpha Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Peter D. Grünwald
A standard practice in statistical hypothesis testing is to mention the P -value alongside the accept/reject decision. We show the advantages of mentioning an e-value instead. With P -values, it is not clear how to use an extreme observation (e.g. P ≪ α ) for getting better frequentist decisions. With e-values it is straightforward, since they provide Type-I risk control in a generalized Neyman–Pearson
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Enhanced effects of species richness on resistance and resilience of global tree growth to prolonged drought Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Yun-Hao Bai, Zhiyao Tang
The increasing duration of drought induced by global climate change has reduced forest productivity. Biodiversity is believed to mitigate the effects of drought, thereby enhancing the stability of tree growth. However, the effects of species richness on tree growth stability under droughts with different durations remain uncertain. Here, we used tree ring data from 4,072 sites globally, combined with
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Genome of Halimeda opuntia reveals differentiation of subgenomes and molecular bases of multinucleation and calcification in algae Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Hao Zhang, Xin Wang, Meng Qu, Haiyan Yu, Jianping Yin, Xiaochuan Liu, Yuhong Liu, Bo Zhang, Yanhong Zhang, Zhangliang Wei, Fangfang Yang, Jingtian Wang, Chengcheng Shi, Guangyi Fan, Jun Sun, Lijuan Long, David A. Hutchins, Chris Bowler, Senjie Lin, Dazhi Wang, Qiang Lin
Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated
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Genetic variation drives cancer cell adaptation to ECM stiffness Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Ting-Ching Wang, Suchitaa Sawhney, Daylin Morgan, Richard L. Bennett, Richa Rashmi, Marcos R. Estecio, Amy Brock, Irtisha Singh, Charles F. Baer, Jonathan D. Licht, Tanmay P. Lele
The progression of many solid tumors is accompanied by temporal and spatial changes in the stiffness of the extracellular matrix (ECM). Cancer cells adapt to soft and stiff ECM through mechanisms that are not fully understood. It is well known that there is significant genetic heterogeneity from cell to cell in tumors, but how ECM stiffness as a parameter might interact with that genetic variation
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Humans flexibly integrate social information despite interindividual differences in reward Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Alexandra Witt, Wataru Toyokawa, Kevin N. Lala, Wolfgang Gaissmaier, Charley M. Wu
There has been much progress in understanding human social learning, including recent studies integrating social information into the reinforcement learning framework. Yet previous studies often assume identical payoffs between observer and demonstrator, overlooking the diversity of social information in real-world interactions. We address this gap by introducing a socially correlated bandit task that
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Physical extraction of antigen and information Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-20 Hongda Jiang, Shenshen Wang
To respond and adapt, cells use surface receptors to sense environmental cues. While biochemical signal processing inside the cell is studied in depth, less is known about how physical processes during cell–cell contact impact signal acquisition. New experiments found that fast-evolving immune B cells in germinal centers (GCs) apply force to acquire antigen clusters prior to internalization, suggesting
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Nuclear dualism without extensive DNA elimination in the ciliate Loxodes magnus Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Brandon K. B. Seah, Aditi Singh, David E. Vetter, Christiane Emmerich, Moritz Peters, Volker Soltys, Bruno Huettel, Estienne C. Swart
Most eukaryotes have one nucleus and nuclear genome per cell. Ciliates have instead evolved distinct nuclei that coexist in each cell: a silent germline vs. transcriptionally active somatic nuclei. In the best-studied model species, both nuclei can divide asexually, but only germline nuclei undergo meiosis and karyogamy during sex. Thereafter, thousands of DNA segments, called internally eliminated
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Unraveling the genomic diversity and admixture history of captive tigers in the United States Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Ellie E. Armstrong, Jazlyn A. Mooney, Katherine A. Solari, Bernard Y. Kim, Gregory S. Barsh, Victoria B. Grant, Gili Greenbaum, Christopher B. Kaelin, Katya Panchenko, Joseph K. Pickrell, Noah Rosenberg, Oliver A. Ryder, Tsuya Yokoyama, Uma Ramakrishnan, Dmitri A. Petrov, Elizabeth A. Hadly
Genomic studies of endangered species have primarily focused on describing diversity patterns and resolving phylogenetic relationships, with the overarching goal of informing conservation efforts. However, few studies have investigated genomic diversity housed in captive populations. For tigers ( Panthera tigris ), captive individuals vastly outnumber those in the wild, but their diversity remains
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The discovery and development of GLP-1 based drugs that have revolutionized the treatment of obesity Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Jeffrey M. Friedman
The 2024 Lasker~DeBakey Clinical Medical Research Award has been given to Joel Habener and Svetlana Mojsov for their discovery of a new hormone GLP-1(7-37) and to Lotte Knudsen for her role in developing sustained acting versions of this hormone as a treatment for obesity. Each of the three had a distinct set of skills that made this advance possible; Habener is an endocrinologist and molecular biologist
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Fructose-2,6-bisphosphate restores DNA repair activity of PNKP and ameliorates neurodegenerative symptoms in Huntington’s disease Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Anirban Chakraborty, Sravan Gopalkrishnashetty Sreenivasmurthy, Wyatt Miller, Weihan Huai, Tapan Biswas, Santi Mohan Mandal, Lisardo Boscá, Balaji Krishnan, Gourisankar Ghosh, Tapas Hazra
Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3) are the two most prevalent polyglutamine (polyQ) neurodegenerative diseases, caused by CAG (encoding glutamine) repeat expansion in the coding region of the huntingtin (HTT) and ataxin-3 (ATXN3) proteins, respectively. We have earlier reported that the activity, but not the protein level, of an essential DNA repair enzyme, polynucleotide
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Meandering conduction channels and the tunable nature of quantized charge transport Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Benoit Douçot, Dmitry Kovrizhin, Roderich Moessner
The discovery of the quantum Hall effect has established the foundation of the field of topological condensed matter physics. An amazingly accurate quantization of the Hall conductance, now enshrined in quantum metrology, is stable against any reasonable perturbation due to its topological protection. Conversely, the latter implies a form of censorship by concealing any local information from the observer
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Differential roles of kinetic on- and off-rates in T-cell receptor signal integration revealed with a modified Fab’-DNA ligand Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Kiera B. Wilhelm, Anand Vissa, Jay T. Groves
Antibody-derived T-cell receptor (TCR) agonists are commonly used to activate T cells. While antibodies can trigger TCRs regardless of clonotype, they bypass native T cell signal integration mechanisms that rely on monovalent, membrane-associated, and relatively weakly binding ligand in the context of cellular adhesion. Commonly used antibodies and their derivatives bind much more strongly than native
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Evolution of pH-sensitive transcription termination in Escherichia coli during adaptation to repeated long-term starvation Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Sarah B. Worthan, Robert D. P. McCarthy, Mildred Delaleau, Ryan Stikeleather, Benjamin P. Bratton, Marc Boudvillain, Megan G. Behringer
Fluctuating environments that consist of regular cycles of co-occurring stress are a common challenge faced by cellular populations. For a population to thrive in constantly changing conditions, an ability to coordinate a rapid cellular response is essential. Here, we identify a mutation conferring an arginine-to-histidine (Arg to His) substitution in the transcription terminator Rho. The rho R109H
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Unraveling the origin of Kondo-like behavior in the 3 d -electron heavy-fermion compound YFe 2 Ge 2 Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Bing Xu, Rui Liu, Hongliang Wo, Zhiyu Liao, Shaohui Yi, Chunhong Li, Jun Zhao, Xianggang Qiu, Zhiping Yin, Christian Bernhard
The heavy fermion (HF) state of d -electron systems is of great current interest since it exhibits various exotic phases and phenomena that are reminiscent of the Kondo effect in f -electron HF systems. Here, we present a combined infrared spectroscopy and first-principles band structure calculation study of the 3 d -electron HF compound YFe 2 Ge 2 . The infrared response exhibits several charge-dynamical
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Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Wanqian Li, Siyuan He, Jun Tan, Na Li, Chenyang Zhao, Xiaotang Wang, Zhi Zhang, Jiangyi Liu, Jiaxing Huang, Xingran Li, Qian Zhou, Ke Hu, Peizeng Yang, Shengping Hou
Uveitis is a vision-threatening disease primarily driven by a dysregulated immune response, with retinal microglia playing a pivotal role in its progression. Although the transcription factor EGR2 is known to be closely associated with uveitis, including Vogt–Koyanagi–Harada disease and Behcet’s disease, and is essential for maintaining the dynamic homeostasis of autoimmunity, its exact role in uveitis
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Revisiting the four Hexapoda classes: Protura as the sister group to all other hexapods Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Shiyu Du, Erik Tihelka, Daoyuan Yu, Wan-Jun Chen, Yun Bu, Chenyang Cai, Michael S. Engel, Yun-Xia Luan, Feng Zhang
Insects represent the most diverse animal group, yet previous phylogenetic analyses based on morphological and molecular data have failed to agree on the evolutionary relationships of early insects and their six-legged relatives (together constituting the clade Hexapoda). In particular, the phylogenetic positions of the three early-diverging hexapod lineages—the coneheads (Protura), springtails (Collembola)
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Phosphorescent metallaknots of Au(I)-bis(acetylide) strands directed by Cu(I) π-coordination Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Ya-Zi Huang, Raorao Yang, Liang Zhang, Zhong-Ning Chen
Knots containing metal atoms as part of their continuous strand backbone are termed as metallaknots. While several metallaknots have been synthesized through one-pot self-assembly, the designed synthesis of metallaknots by controlling the arrangement of entanglements and strands connectivity remains unexplored. Here, we report the synthesis of metallaknots composed with Au(I)-bis(acetylide) linkages
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In vivo CRISPR screens identify Mga as an immunotherapy target in triple-negative breast cancer Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Xu Feng, Chang Yang, Yuanjian Huang, Dan Su, Chao Wang, Lori Lyn Wilson, Ling Yin, Mengfan Tang, Siting Li, Zhen Chen, Dandan Zhu, Shimin Wang, Shengzhe Zhang, Jie Zhang, Huimin Zhang, Litong Nie, Min Huang, Jae-Il Park, Traver Hart, Dadi Jiang, Kuirong Jiang, Junjie Chen
Immune evasion is not only critical for tumor initiation and progression, but also determines the efficacy of immunotherapies. Through iterative in vivo CRISPR screens with seven syngeneic tumor models, we identified core and context-dependent immune evasion pathways across cancer types. This valuable high-confidence dataset is available for the further understanding of tumor intrinsic immunomodulators
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Nanoscale dynamics of the cadherin–catenin complex bound to vinculin revealed by neutron spin echo spectroscopy Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 David J. E. Callaway, Iain D. Nicholl, Bright Shi, Gilbert Reyes, Bela Farago, Zimei Bu
We report a neutron spin echo (NSE) study of the nanoscale dynamics of the cell–cell adhesion cadherin–catenin complex bound to vinculin. Our measurements and theoretical physics analyses of the NSE data reveal that the dynamics of full-length α-catenin, β-catenin, and vinculin residing in the cadherin–catenin–vinculin complex become activated, involving nanoscale motions in this complex. The cadherin–catenin
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Effect of a cash transfer intervention on memory decline and dementia probability in older adults in rural South Africa. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Molly Rosenberg,Erika T Beidelman,Xiwei Chen,Chodziwadziwa Whiteson Kabudula,Audrey Pettifor,Darina T Bassil,Lisa Berkman,Kathleen Kahn,Stephen Tollman,Lindsay C Kobayashi
Evidence on cash transfers as a population-level intervention to support healthy cognitive aging in low-income settings is sparse. We assessed the effect of a cash transfer intervention on cognitive aging outcomes in older South African adults. We leveraged the overlap in the sampling frames of a Phase 3 randomized cash transfer trial [HIV Prevention Trial Network (HPTN) 068, 2011-2015] and an aging
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Oligomerization-driven avidity correlates with SARS-CoV-2 cellular binding and inhibition. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Roi Asor,Anna Olerinyova,Sean A Burnap,Manish S Kushwah,Fabian Soltermann,Lucas S P Rudden,Mario Hensen,Snežana Vasiljevic,Juliane Brun,Michelle Hill,Liu Chang,Wanwisa Dejnirattisai,Piyada Supasa,Juthathip Mongkolsapaya,Daming Zhou,David I Stuart,Gavin R Screaton,Matteo T Degiacomi,Nicole Zitzmann,Justin L P Benesch,Weston B Struwe,Philipp Kukura
Cellular processes are controlled by the thermodynamics of the underlying biomolecular interactions. Frequently, structural investigations use one monomeric binding partner, while ensemble measurements of binding affinities generally yield one affinity representative of a 1:1 interaction, despite the majority of the proteome consisting of oligomeric proteins. For example, viral entry and inhibition
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Akira Endo, who discovered a "penicillin" for heart attacks (1933 to 2024). Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Joseph L Goldstein,Michael S Brown
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Naturalized species drive functional trait shifts in plant communities. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Magda Garbowski,Daniel C Laughlin,Dana M Blumenthal,Helen R Sofaer,David T Barnett,Evelyn M Beaury,Daniel M Buonaiuto,Jeffrey D Corbin,Jeffrey S Dukes,Regan Early,Andrea N Nebhut,Laís Petri,Montserrat Vilà,Ian S Pearse
Despite decades of research documenting the consequences of naturalized and invasive plant species on ecosystem functions, our understanding of the functional underpinnings of these changes remains rudimentary. This is partially due to ineffective scaling of trait differences between native and naturalized species to whole plant communities. Working with data from over 75,000 plots and over 5,500 species
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Hunting down the elusive cytosolic-DNA sensor Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-19 Diane Mathis
The 2024 Albert Lasker Basic Medical Research Award was attributed to Zhijian (James) Chen for “the discovery of the cGAS enzyme that senses foreign and self DNA, solving the mystery of how DNA stimulates immune and inflammatory responses.” Bringing to bear an ingenious in vitro complementation system, an astute insight, and superlative biochemistry, Chen and colleagues identified cGAS (cGAMP synthase)
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In This Issue Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17
Proceedings of the National Academy of Sciences, Volume 121, Issue 38, September 2024.
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On the anniversary of the Maui fires, a call for Indigenous land care to mitigate future disasters. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 D Nākoa Farrant,Clay Trauernicht,Aurora Kagawa-Viviani,Thomas W Giambelluca,Carla M D'Antonio
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Actomyosin contraction in the follicular epithelium provides the major mechanical force for follicle rupture during Drosophila ovulation Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Stella E. Cho, Wei Li, Andrew M. Beard, Jonathan A. Jackson, Risa Kiernan, Kazunori Hoshino, Adam C. Martin, Jianjun Sun
Ovulation is critical for sexual reproduction and consists of the process of liberating fertilizable oocytes from their somatic follicle capsules, also known as follicle rupture. The mechanical force for oocyte expulsion is largely unknown in many species. Our previous work demonstrated that Drosophila ovulation, as in mammals, requires the proteolytic degradation of the posterior follicle wall and
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Etiology of craniofacial and cardiac malformations in a mouse model of SF3B4 -related syndromes Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Shruti Kumar, Eric Bareke, Jimmy Lee, Emma Carlson, Fjodor Merkuri, Evelyn E. Schwager, Steven Maglio, Jennifer L. Fish, Jacek Majewski, Loydie A. Jerome-Majewska
Pathogenic variants in SF3B4, a component of the U2 snRNP complex important for branchpoint sequence recognition and splicing, are responsible for the acrofacial disorders Nager and Rodriguez Syndrome, also known as SF3B4 -related syndromes. Patients exhibit malformations in the head, face, limbs, vertebrae as well as the heart. To uncover the etiology of craniofacial malformations found in SF3B4 -related
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Atomic-engineered gradient tunable solid-state metamaterials Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Zhiyuan Yan, Albertus Denny Handoko, Weikang Wu, Chuchu Yang, Hao Wang, Meltem Yilmaz, Zhiyong Zhang, Libo Cheng, Xinbin Cheng, Ghim Wei Ho, Bin Feng, Naoya Shibata, Rong Zhao, Joel K. W. Yang, Chong Tow Chong, Yuichi Ikuhara, Cheng-Wei Qiu
Metamaterial has been captivated a popular notion, offering photonic functionalities beyond the capabilities of natural materials. Its desirable functionality primarily relies on well-controlled conditions such as structural resonance, dispersion, geometry, filling fraction, external actuation, etc. However, its fundamental building blocks—meta-atoms—still rely on naturally occurring substances. Here
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Lipin1 depletion coordinates neuronal signaling pathways to promote motor and sensory axon regeneration after spinal cord injury Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Weitao Chen, Junqiang Wu, Chao Yang, Suying Li, Zhewei Liu, Yongyan An, Xuejie Wang, Jiaming Cao, Jiahui Xu, Yangyang Duan, Xue Yuan, Xin Zhang, Yiren Zhou, Jacque Pak Kan Ip, Amy K. Y. Fu, Nancy Y. Ip, Zhongping Yao, Kai Liu
Adult central nervous system (CNS) neurons down-regulate growth programs after injury, leading to persistent regeneration failure. Coordinated lipids metabolism is required to synthesize membrane components during axon regeneration. However, lipids also function as cell signaling molecules. Whether lipid signaling contributes to axon regeneration remains unclear. In this study, we showed that lipin1
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Transdifferentiation occurs without resetting development-specific DNA methylation, a key determinant of full-function cell identity Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Ahmed Radwan, Jason Eccleston, Ofra Sabag, Howard Marcus, Jonathan Sussman, Alberto Ouro, Moran Rahamim, Meir Azagury, Batia Azria, Ben Z. Stanger, Howard Cedar, Yosef Buganim
A number of studies have demonstrated that it is possible to directly convert one cell type to another by factor-mediated transdifferentiation, but in the vast majority of cases, the resulting reprogrammed cells are unable to maintain their new cell identity for prolonged culture times and have a phenotype only partially similar to their endogenous counterparts. To better understand this phenomenon
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The p53 target DRAM1 modulates calcium homeostasis and ER stress by promoting contact between lysosomes and the ER through STIM1 Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Xiying Wang, Ji Geng, Suman Rimal, Yuxiu Sui, Jie Pan, Zhenghong Qin, Bingwei Lu
It is well established that DNA Damage Regulated Autophagy Modulator 1 (DRAM1), a lysosomal protein and a target of p53, participates in autophagy. The cellular functions of DRAM1 beyond autophagy remain elusive. Here, we show p53-dependent upregulation of DRAM1 in mitochondrial damage–induced Parkinson’s disease (PD) models and exacerbation of disease phenotypes by DRAM1. We find that the lysosomal
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The androgen receptor in mesenchymal progenitors regulates skeletal muscle mass via Igf1 expression in male mice Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Hiroshi Sakai, Hideaki Uno, Harumi Yamakawa, Kaori Tanaka, Aoi Ikedo, Akiyoshi Uezumi, Yasuyuki Ohkawa, Yuuki Imai
Androgens exert their effects primarily by binding to the androgen receptor (AR), a ligand-dependent nuclear receptor. While androgens have anabolic effects on skeletal muscle, previous studies reported that AR functions in myofibers to regulate skeletal muscle quality, rather than skeletal muscle mass. Therefore, the anabolic effects of androgens are exerted via nonmyofiber cells. In this context
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Measurement of adhesion and traction of cells at high yield reveals an energetic ratchet operating during nephron condensation Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Jiageng Liu, Louis S. Prahl, Aria Zheyuan Huang, Alex J. Hughes
Developmental biology-inspired strategies for tissue-building have extraordinary promise for regenerative medicine, spurring interest in the relationship between cell biophysical properties and morphological transitions. However, mapping gene or protein expression data to cell biophysical properties to physical morphogenesis remains challenging with current techniques. Here, we present m ultiplexed
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The Pentamer glycoprotein complex inhibits viral Immediate Early transcription during Human Cytomegalovirus infections Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Michael S. Ohman, Emily R. Albright, Christopher B. Gelbmann, Robert F. Kalejta
The Pentamer complex of Human Cytomegalovirus (HCMV) consists of the viral glycoproteins gH, gL, UL128, UL130, and UL131 and is incorporated into infectious virions. HCMV strains propagated extensively in vitro in fibroblasts carry UL128, UL130, or UL131 alleles that do not make a functional complex and thus lack Pentamer function. Adding functional Pentamer to such strains decreases virus growth in
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Spatiotemporal formation of a single liquid-like condensate and amyloid fibrils of α-synuclein by optical trapping at solution surface Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Keisuke Yuzu, Ching-Yang Lin, Po-Wei Yi, Chih-Hao Huang, Hiroshi Masuhara, Eri Chatani
Liquid-like protein condensates have recently attracted much attention due to their critical roles in biological phenomena. They typically show high fluidity and reversibility for exhibiting biological functions, while occasionally serving as sites for the formation of amyloid fibrils. To comprehend the properties of protein condensates that underlie biological function and pathogenesis, it is crucial
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A molten globule ensemble primes Arf1–GDP for the nucleotide switch Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-18 Tejaswi Koduru, Noam Hantman, Edgar V. Peters, Michel W. Jaworek, Jinqiu Wang, Siwen Zhang, Scott A. McCallum, Richard E. Gillilan, Martin J. Fossat, Christian Roumestand, Amin Sagar, Roland Winter, Pau Bernadó, Jacqueline Cherfils, Catherine A. Royer
The adenosine di-phosphate (ADP) ribosylation factor (Arf) small guanosine tri-phosphate (GTP)ases function as molecular switches to activate signaling cascades that control membrane organization in eukaryotic cells. In Arf1, the GDP/GTP switch does not occur spontaneously but requires guanine nucleotide exchange factors (GEFs) and membranes. Exchange involves massive conformational changes, including
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The primary cilium of cholinergic neurons may be a linchpin in the progression of Parkinson's Disease. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Santiago Uribe-Cano,Andreas H Kottmann
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Conformational ensembles in Klebsiella pneumoniae FimH impact uropathogenesis Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Edward D. B. Lopatto, Jerome S. Pinkner, Denise A. Sanick, Robert F. Potter, Lily X. Liu, Jesús Bazán Villicaña, Kevin O. Tamadonfar, Yijun Ye, Maxwell I. Zimmerman, Nathaniel C. Gualberto, Karen W. Dodson, James W. Janetka, David A. Hunstad, Scott J. Hultgren
Klebsiella pneumoniae is an important pathogen causing difficult-to-treat urinary tract infections (UTIs). Over 1.5 million women per year suffer from recurrent UTI, reducing quality of life and causing substantial morbidity and mortality, especially in the hospital setting. Uropathogenic E. coli (UPEC) is the most prevalent cause of UTI. Like UPEC, K. pneumoniae relies on type 1 pili, tipped with
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Neural network architecture of a mammalian brain Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Larry W. Swanson, Joel D. Hahn, Olaf Sporns
Connectomics research is making rapid advances, although models revealing general principles of connectional architecture are far from complete. Our analysis of 10 6 published connection reports indicates that the adult rat brain interregional connectome has about 76,940 of a possible 623,310 axonal connections between its 790 gray matter regions mapped in a reference atlas, equating to a network density
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Utilizing big data without domain knowledge impacts public health decision-making Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Miao Zhang, Salman Rahman, Vishwali Mhasawade, Rumi Chunara
New data sources and AI methods for extracting information are increasingly abundant and relevant to decision-making across societal applications. A notable example is street view imagery, available in over 100 countries, and purported to inform built environment interventions (e.g., adding sidewalks) for community health outcomes. However, biases can arise when decision-making does not account for
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Inequality aversion predicts support for public and private redistribution Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Thomas F. Epper, Ernst Fehr, Claus Thustrup Kreiner, Søren Leth-Petersen, Isabel Skak Olufsen, Peer Ebbesen Skov
Rising inequality has brought redistribution back on the political agenda. In theory, inequality aversion drives people’s support for redistribution. People can dislike both advantageous inequality (comparison relative to those worse off) and disadvantageous inequality (comparison relative to those better off). Existing experimental evidence reveals substantial variation across people in these preferences
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Atomistic mechanisms of the regulation of small-conductance Ca 2+ -activated K + channel (SK2) by PIP2 Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Ryan L. Woltz, Yang Zheng, Woori Choi, Khoa Ngo, Pauline Trinh, Lu Ren, Phung N. Thai, Brandon J. Harris, Yanxiao Han, Kyle C. Rouen, Diego Lopez Mateos, Zhong Jian, Ye Chen-Izu, Eamonn J. Dickson, Ebenezer N. Yamoah, Vladimir Yarov-Yarovoy, Igor Vorobyov, Xiao-Dong Zhang, Nipavan Chiamvimonvat
Small-conductance Ca 2+ -activated K + channels (SK, K Ca 2) are gated solely by intracellular microdomain Ca 2+ . The channel has emerged as a therapeutic target for cardiac arrhythmias. Calmodulin (CaM) interacts with the CaM binding domain (CaMBD) of the SK channels, serving as the obligatory Ca 2+ sensor to gate the channels. In heterologous expression systems, phosphatidylinositol 4,5-bisphosphate
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Hippo effector, Yorkie, is a tumor suppressor in select Drosophila squamous epithelia Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Rachita Bhattacharya, Jaya Kumari, Shweta Banerjee, Jyoti Tripathi, Saurabh Singh Parihar, Nitin Mohan, Pradip Sinha
Mammalian Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) and Drosophila Yorkie (Yki) are transcription cofactors of the highly conserved Hippo signaling pathway. It has been long assumed that the YAP/TAZ/Yki signaling drives cell proliferation during organ growth. However, its instructive role in regulating developmentally programmed organ growth, if any,
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Microbial community interactions on a chip Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Duane S. Juang, Wren E. Wightman, Gabriel L. Lozano, Terry D. Juang, Layla J. Barkal, Jiaquan Yu, Manuel F. Garavito, Amanda Hurley, Ophelia S. Venturelli, Jo Handelsman, David J. Beebe
Multispecies microbial communities drive most ecosystems on Earth. Chemical and biological interactions within these communities can affect the survival of individual members and the entire community. However, the prohibitively high number of possible interactions within a microbial community has made the characterization of factors that influence community development challenging. Here, we report
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Agonist antibody to MuSK protects mice from MuSK myasthenia gravis Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Julien Oury, Begona Gamallo-Lana, Leah Santana, Christophe Steyaert, Dana L. E. Vergoossen, Adam C. Mar, Bernhardt Vankerckhoven, Karen Silence, Roeland Vanhauwaert, Maartje G. Huijbers, Steven J. Burden
Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). MuSK, a master regulator of NMJ development
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Manipulation of natural transformation by AbaR-type islands promotes fixation of antibiotic resistance in Acinetobacter baumannii Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Rémi Tuffet, Gabriel Carvalho, Anne-Sophie Godeux, Fanny Mazzamurro, Eduardo P. C. Rocha, Maria-Halima Laaberki, Samuel Venner, Xavier Charpentier
The opportunistic pathogen Acinetobacter baumannii , carries variants of A. baumannii resistance islands (AbaR)-type genomic islands conferring multidrug resistance. Their pervasiveness in the species has remained enigmatic. The dissemination of AbaRs is intricately linked to their horizontal transfer via natural transformation, a process through which bacteria can import and recombine exogenous DNA
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Glial swip-10 controls systemic mitochondrial function, oxidative stress, and neuronal viability via copper ion homeostasis Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Peter Rodriguez, Vrinda Kalia, Cristina Fenollar-Ferrer, Chelsea L. Gibson, Zayna Gichi, Andre Rajoo, Carson D. Matier, Aidan T. Pezacki, Tong Xiao, Lucia Carvelli, Christopher J. Chang, Gary W. Miller, Andy V. Khamoui, Jana Boerner, Randy D. Blakely
Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly reliant on mitochondrial production of ATP, with many neurodegenerative diseases, including Parkinson’s disease, associated with diminished mitochondrial function. The gene MBLAC1 encodes a ribonuclease
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Refractive lensing of scintillating FRBs by subparsec cloudlets in the multiphase CGM Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-17 Dylan L. Jow, Xiaohan Wu, Ue-Li Pen
We consider the refractive lensing effects of ionized cool ( T ∼ 10 4 K ) gas cloudlets in the circumgalactic medium (CGM) of galaxies. In particular, we discuss the combined effects of lensing from these cloudlets and scintillation from plasma screens in the Milky Way interstellar medium (ISM). We show that, if the CGM comprises a mist of subparsec cloudlets with column densities of order 10 17 cm
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Response to Allard: A minor (albeit significant) role for voltage-induced calcium release in Caenorhabditis elegans muscles. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-16 Luna Gao,Evan Ardiel,Stephen Nurrish,Joshua M Kaplan
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Causal interpretations of family GWAS in the presence of heterogeneous effects Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-13 Carl Veller, Molly Przeworski, Graham Coop
Family-based genome-wide association studies (GWASs) are often claimed to provide an unbiased estimate of the average causal effects (or average treatment effects; ATEs) of alleles, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. We show that this claim does not hold in general. Because Mendelian segregation only randomizes
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Hierarchical communities in the larval Drosophila connectome: Links to cellular annotations and network topology Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-13 Richard Betzel, Maria Grazia Puxeddu, Caio Seguin
One of the longstanding aims of network neuroscience is to link a connectome’s topological properties—i.e., features defined from connectivity alone–with an organism’s neurobiology. One approach for doing so is to compare connectome properties with annotational maps. This type of analysis is popular at the meso-/macroscale, but is less common at the nano-scale, owing to a paucity of neuron-level connectome
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Evolution of the substrate specificity of an RNA ligase ribozyme from phosphorimidazole to triphosphate activation Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-13 Saurja DasGupta, Zoe Weiss, Collin Nisler, Jack W. Szostak
The acquisition of new RNA functions through evolutionary processes was essential for the diversification of RNA-based primordial biology and its subsequent transition to modern biology. However, the mechanisms by which RNAs access new functions remain unclear. Do RNA enzymes need completely new folds to support new but related functions, or is reoptimization of the active site sufficient? What are