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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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Unraveling the origin of Kondo-like behavior in the 3d-electron heavy-fermion compound YFe2Ge2. 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 [Formula: see text]-electron systems is of great current interest since it exhibits various exotic phases and phenomena that are reminiscent of the Kondo effect in [Formula: see text]-electron HF systems. Here, we present a combined infrared spectroscopy and first-principles band structure calculation study of the [Formula: see text]-electron HF compound YFe[Formula:
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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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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
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Spontaneous assembly of condensate networks during the demixing of structured fluids Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-13 Yuma Morimitsu, Christopher A. Browne, Zhe Liu, Paul G. Severino, Manesh Gopinadhan, Eric B. Sirota, Ozcan Altintas, Kazem V. Edmond, Chinedum O. Osuji
Liquid–liquid phase separation, whereby two liquids spontaneously demix, is ubiquitous in industrial, environmental, and biological processes. While isotropic fluids are known to condense into spherical droplets in the binodal region, these dynamics are poorly understood for structured fluids. Here, we report the unique observation of condensate networks, which spontaneously assemble during the demixing
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Machine learning reveals the transcriptional regulatory network and circadian dynamics of Synechococcus elongatus PCC 7942 Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-13 Yuan Yuan, Tahani Al Bulushi, Anand V. Sastry, Cigdem Sancar, Richard Szubin, Susan S. Golden, Bernhard O. Palsson
Synechococcus elongatus is an important cyanobacterium that serves as a versatile and robust model for studying circadian biology and photosynthetic metabolism. Its transcriptional regulatory network (TRN) is of fundamental interest, as it orchestrates the cell’s adaptation to the environment, including its response to sunlight. Despite the previous characterization of constituent parts of the S. elongatus
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Maxine Singer: A laser-sharp intellect with a passion for science. Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Susanne Garvey
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The roles of geometry and viscosity in the mobilization of coarse sediment by finer sediment Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Marwan A. Hassan, Gary Parker, Yarra Hassan, Chenge An, Xudong Fu, Jeremy G. Venditti
In rivers, the addition of finer sediment to a coarser riverbed is known to increase the mobility of the coarser fraction. Two mechanisms have been suggested for this: a geometric mechanism whereby smaller sizes smooth the bed, increasing near-bed velocity and thus mobility of the larger sizes, and a viscous mechanism whereby a transitionally smooth turbulent boundary layer forms, rendering the coarser
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How bacteria actively use passive physics to make biofilms Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Liraz Chai, Vasily Zaburdaev, Roberto Kolter
Modern molecular microbiology elucidates the organizational principles of bacterial biofilms via detailed examination of the interplay between signaling and gene regulation. A complementary biophysical approach studies the mesoscopic dependencies at the cellular and multicellular levels with a distinct focus on intercellular forces and mechanical properties of whole biofilms. Here, motivated by recent
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Host-derived CEACAM-laden vesicles engage enterotoxigenic Escherichia coli for elimination and toxin neutralization Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Alaullah Sheikh, Debayan Ganguli, Tim J. Vickers, Bernhard B. Singer, Jennifer Foulke-Abel, Marjahan Akhtar, Nazia Khatoon, Bipul Setu, Supratim Basu, Clayton Harro, Nicole Maier, Wandy L. Beatty, Subhra Chakraborty, Taufiqur R. Bhuiyan, Firdausi Qadri, Mark Donowitz, James M. Fleckenstein
Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile
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Encoding innate ability through a genomic bottleneck Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Sergey Shuvaev, Divyansha Lachi, Alexei Koulakov, Anthony Zador
Animals are born with extensive innate behavioral capabilities, which arise from neural circuits encoded in the genome. However, the information capacity of the genome is orders of magnitude smaller than that needed to specify the connectivity of an arbitrary brain circuit, indicating that the rules encoding circuit formation must fit through a “genomic bottleneck” as they pass from one generation
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N-degron pathways Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Alexander Varshavsky
An N-degron is a degradation signal whose main determinant is a “destabilizing” N-terminal residue of a protein. Specific N-degrons, discovered in 1986, were the first identified degradation signals in short-lived intracellular proteins. These N-degrons are recognized by a ubiquitin-dependent proteolytic system called the Arg/N-degron pathway. Although bacteria lack the ubiquitin system, they also
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Deformation dynamics of nanopores upon water imbibition Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Juan Sanchez, Lars Dammann, Laura Gallardo, Zhuoqing Li, Michael Fröba, Robert H. Meißner, Howard A. Stone, Patrick Huber
Capillarity-driven transport in nanoporous solids is widespread in nature and crucial for modern liquid-infused engineering materials. During imbibition, curved menisci driven by high negative Laplace pressures exert an enormous contractile load on the porous matrix. Due to the challenge of simultaneously monitoring imbibition and deformation with high spatial resolution, the resulting coupling of
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Blobs form during the single-file transport of proteins across nanopores Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-12 Adina Sauciuc, Jacob Whittaker, Matthijs Tadema, Katarzyna Tych, Albert Guskov, Giovanni Maglia
The transport of biopolymers across nanopores is an important biological process currently under investigation for the rapid analysis of DNA and proteins. While the transport of DNA is generally understood, methods to induce unfolded protein translocation have only recently been discovered (Yu et al., 2023, Sauciuc et al., 2023). Here, we found that during electroosmotically driven translocation of
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Correction for Bao et al., Sugar status in preexisting leaves determines systemic stomatal development within newly developing leaves Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-06
Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.
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Plasma cell-free RNA signatures of inflammatory syndromes in children Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-06 Conor J. LoyVenice ServellitaAlicia Sotomayor-GonzalezAndrew BlissJoan S. LenzEmma BelcherWill SuslovicJenny NguyenMeagan E. WilliamsMiriam OsegueraMichael A. GardinerJong-Ha ChoiHui-Mien HsiaoHao WangJihoon KimChisato ShimizuAdriana H. TremouletMeghan DelaneyRoberta L. DeBiasiChristina A. RostadJane C. BurnsCharles Y. ChiuIwijn De VlaminckaMeinig School of Biomedical Engineering, Cornell University
Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.
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In This Issue Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-10
Proceedings of the National Academy of Sciences, Volume 121, Issue 37, September 2024.
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Localization–delocalization transition for light particles in turbulence Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-11 Ziqi Wang, Xander M. de Wit, Federico Toschi
Small bubbles in fluids rise to the surface due to Archimede’s force. Remarkably, in turbulent flows this process is severely hindered by the presence of vortex filaments, which act as moving potential wells, dynamically trapping light particles and bubbles. Quantifying the statistical weights and roles of vortex filaments in turbulence is, however, still an outstanding experimental and computational
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FicD sensitizes cellular response to glucose fluctuations in mouse embryonic fibroblasts Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-11 Burak Gulen, Aubrie Blevins, Lisa N. Kinch, Kelly A. Servage, Nathan M. Stewart, Hillery F. Gray, Amanda K. Casey, Kim Orth
During homeostasis, the endoplasmic reticulum (ER) maintains productive transmembrane and secretory protein folding that is vital for proper cellular function. The ER-resident HSP70 chaperone, binding immunoglobulin protein (BiP), plays a pivotal role in sensing ER stress to activate the unfolded protein response (UPR). BiP function is regulated by the bifunctional enzyme filamentation induced by cyclic-AMP
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Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-11 Rosanna P. Baker, Amy Z. Liu, Arturo Casadevall
Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated
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The role of the water contact layer on hydration and transport at solid/liquid interfaces Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-11 J. Gäding, V. Della Balda, J. Lan, J. Konrad, M. Iannuzzi, R. H. Meißner, G. Tocci
Understanding the structure in the nanoscopic region of water that is in direct contact with solid surfaces, so-called contact layer, is key to quantifying macroscopic properties that are of interest to e.g. catalysis, ice nucleation, nanofluidics, gas adsorption, and sensing. We explore the structure of the water contact layer on various technologically relevant solid surfaces, namely graphene, MoS
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Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1 Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-11 Yu Liu, Chenghan Li, J. Alfredo Freites, Douglas J. Tobias, Gregory A. Voth
Human voltage-gated proton (hHv1) channels are crucial for regulating essential biological processes such as immune cell respiratory burst, sperm capacitation, and cancer cell migration. Despite the significant concentration difference between protons and other ions in physiological conditions, hHv1 demonstrates remarkable proton selectivity. Our calculations of single-proton, cation, and anion permeation
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Commutative avatars of representations of semisimple Lie groups Proc. Natl. Acad. Sci. U.S.A. (IF 9.4) Pub Date : 2024-09-11 Tamás Hausel
Here we announce the construction and properties of a big commutative subalgebra of the Kirillov algebra attached to a finite dimensional irreducible representation of a complex semisimple Lie group. They are commutative finite flat algebras over the cohomology of the classifying space of the group. They are isomorphic with the equivariant intersection cohomology of affine Schubert varieties, endowing