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Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Xing Liu, Chunchun Zhu, Shuke Jia, Hongyan Deng, Jinhua Tang, Xueyi Sun, Xiaoli Zeng, Xiaoyun Chen, Zixuan Wang, Wen Liu, Qian Liao, Huangyuan Zha, Xiaolian Cai, Wuhan Xiao
To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue
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Differences in enantiomeric diffusion can lead to selective chiral amplification Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Jean Gillet, Yves Geerts, Laurence Rongy, Yannick De Decker
A fundamental question associated with chirality is how mixtures containing equal amounts of interconverting enantiomers can spontaneously convert to systems enriched in only one of them. Enantiomers typically have similar chemical properties, but can exhibit distinct reactivity under specific conditions, and these differences can be used to bias the system’s composition in favor of one enantiomer
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A generic approach to infer community-level fitness of microbial genes Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Teng Wang, Andrea Weiss, Lingchong You
The gene content in a metagenomic pool defines the function potential of a microbial community. Natural selection, operating on the level of genomes or genes, shapes the evolution of community functions by enriching some genes while depriving the others. Despite the importance of microbiomes in the environment and health, a general metric to evaluate the community-wide fitness of microbial genes remains
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Dual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Sheng Shu, Yuko Tsutsui, Rajkanwar Nathawat, Wei Mi
Levels of lipopolysaccharide (LPS), an essential glycolipid on the surface of most gram-negative bacteria, are tightly controlled—making LPS synthesis a promising target for developing new antibiotics. Escherichia coli adaptor protein LapB (YciM) plays an important role in regulating LPS synthesis by promoting degradation of LpxC, a deacetylase that catalyzes the first committed step in LPS synthesis
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Microglia-derived extracellular vesicles trigger age-related neurodegeneration upon DNA damage Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Ermioni S. Arvanitaki, Evi Goulielmaki, Katerina Gkirtzimanaki, George Niotis, Edisona Tsakani, Electra Nenedaki, Iliana Rouska, Mary Kefalogianni, Dionysios Xydias, Ilias Kalafatakis, Sotiris Psilodimitrakopoulos, Domna Karagogeos, Björn Schumacher, Emmanuel Stratakis, George A. Garinis
DNA damage and neurodegenerative disorders are intimately linked but the underlying mechanism remains elusive. Here, we show that persistent DNA lesions in tissue-resident macrophages carrying an XPF-ERCC1 DNA repair defect trigger neuroinflammation and neuronal cell death in mice. We find that microglia accumulate dsDNAs and chromatin fragments in the cytosol, which are sensed thereby stimulating
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WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Jun-Li Wang, Ming Wang, Li Zhang, You-Xia Li, Jing-Jing Li, Yu-Yang Li, Zuo-Xian Pu, Dan-Yang Li, Xing-Nan Liu, Wang Guo, Dong-Wei Di, Xiao-Feng Li, Guang-Qin Guo, Lei Wu
Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCF TIR1/AFB -Aux/IAA-ARF pathway and several other less characterized “noncanonical” pathways. Recently, one SCF TIR1/AFB -independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development
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Variation in the relationship between odd isotopes of tin in mass-independent fractionation induced by the magnetic isotope effect Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Yusuke Fukami, Ryoko Ariizumi, Yuta Ijichi, Takeshi Ohno, Teruhiko Kashiwabara, Takazo Shibuya, Katsuhiko Suzuki, Takafumi Hirata
Experimental results are presented showing the variation in the relationship between odd isotopes of tin (Sn) in mass-independent fractionation caused by the magnetic isotope effect (MIE), which has previously only been observed for mercury. These results are consistent with the trend predicted from the difference between the magnitudes of nuclear magnetic moments of odd isotopes with a nuclear spin
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A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Anastasia Knyazeva, Shuang Li, Dale P. Corkery, Kasturika Shankar, Laura K. Herzog, Xuepei Zhang, Birendra Singh, Georg Niggemeyer, David Grill, Jonathan D. Gilthorpe, Massimiliano Gaetani, Lars-Anders Carlson, Herbert Waldmann, Yao-Wen Wu
The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the
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The Myc-associated zinc finger protein epigenetically controls expression of interferon-γ-stimulated genes by recruiting STAT1 to chromatin Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Tiaojiang Xiao, Xin Li, Gary Felsenfeld
The MYC-Associated Zinc Finger Protein (MAZ) plays important roles in chromatin organization and gene transcription regulation. Dysregulated expression of MAZ causes diseases, such as glioblastoma, breast cancer, prostate cancer, and liposarcoma. Previously, it has been reported that MAZ controls the proinflammatory response in colitis and colon cancer via STAT3 signaling, suggesting that MAZ is involved
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Chemical bond reorganization in intramolecular proton transfer revealed by ultrafast X-ray photoelectron spectroscopy Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Yonghao Gu, Haiwang Yong, Bing Gu, Shaul Mukamel
Time-resolved X-ray photoelectron spectroscopy (TR-XPS) is used in a simulation study to monitor the excited state intramolecular proton transfer between oxygen and nitrogen atoms in 2-(iminomethyl)phenol. Real-time monitoring of the chemical bond breaking and forming processes is obtained through the time evolution of excited-state chemical shifts. By employing individual atomic probes of the proton
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Temporal and spatial dynamics of Listeria monocytogenes central nervous system infection in mice Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Victoria Chevée, Karthik Hullahalli, Katherine G. Dailey, Leslie Güereca, Chenyu Zhang, Matthew K. Waldor, Daniel A. Portnoy
Listeria monocytogenes is a bacterial pathogen that can cause life-threatening central nervous system (CNS) infections. While mechanisms by which L. monocytogenes and other pathogens traffic to the brain have been studied, a quantitative understanding of the underlying dynamics of colonization and replication within the brain is still lacking. In this study, we used barcoded L. monocytogenes to quantify
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Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Nisha Mohd Rafiq, Kenshiro Fujise, Martin Shaun Rosenfeld, Peng Xu, Pietro De Camilli
Synaptojanin-1 (SJ1) is a major neuronal-enriched PI(4, 5)P 2 4- and 5-phosphatase implicated in the shedding of endocytic factors during endocytosis. A mutation (R258Q) that impairs selectively its 4-phosphatase activity causes Parkinsonism in humans and neurological defects in mice (SJ1 RQ KI mice). Studies of these mice showed, besides an abnormal assembly state of endocytic factors at synapses
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Spontaneous eye movements reflect the representational geometries of conceptual spaces Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Simone Viganò, Rena Bayramova, Christian F. Doeller, Roberto Bottini
Functional neuroimaging studies indicate that the human brain can represent concepts and their relational structure in memory using coding schemes typical of spatial navigation. However, whether we can read out the internal representational geometries of conceptual spaces solely from human behavior remains unclear. Here, we report that the relational structure between concepts in memory might be reflected
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CNS autoimmune response in the MAM/pilocarpine rat model of epileptogenic cortical malformation Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-18 Massimo Costanza, Arianna Ciotti, Alessandra Consonni, Barbara Cipelletti, Alessandro Cattalini, Cinzia Cagnoli, Fulvio Baggi, Marco de Curtis, Francesca Colciaghi
The development of seizures in epilepsy syndromes associated with malformations of cortical development (MCDs) has traditionally been attributed to intrinsic cortical alterations resulting from abnormal network excitability. However, recent analyses at single-cell resolution of human brain samples from MCD patients have indicated the possible involvement of adaptive immunity in the pathogenesis of
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Reinforcement learning informs optimal treatment strategies to limit antibiotic resistance Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-12 Davis T. WeaverEshan S. KingJeff MaltasJacob G. ScottaCase Western Reserve University School of Medicine, Cleveland, OH 44106bTranslational Hematology Oncology Research, Cleveland Clinic, Cleveland, OH 44106cDepartment of Physics, Case Western Reserve University, Cleveland, OH 44106
Proceedings of the National Academy of Sciences, Volume 121, Issue 16, April 2024.
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Extracellular vesicles released by keratinocytes regulate melanosome maturation, melanocyte dendricity, and pigment transfer Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-12 Marie-Thérèse ProspériCécile GiordanoMireia Gomez-DuroIlse HurbainAnne-Sophie MacéGraça RaposoGisela D’AngeloaInstitut Curie, Paris Sciences & Letters Research University, CNRS, UMR144, Structure and Membrane Compartments, Paris Cedex 05 75248, FrancebInstitut Curie, Paris Sciences & Letters Research University, CNRS, UMR144, Cell and Tissue Imaging Facility (The Cell and Tissue Imaging Platform (PICT-IBiSA))
Proceedings of the National Academy of Sciences, Volume 121, Issue 16, April 2024.
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Emerging roles for ABC transporters as virulence factors in uropathogenic Escherichia coli Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-12 Allyson E. SheaValerie S. ForsythJolie A. StockiTaylor J. MitchellArwen E. Frick-ChengSara N. SmithSicily L. HardyHarry L. T. MobleyaDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109bDepartment of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, AL 36688
Proceedings of the National Academy of Sciences, Volume 121, Issue 16, April 2024.
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Posttranscriptional regulation of FAN1 by miR-124-3p at rs3512 underlies onset-delaying genetic modification in Huntington’s disease Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-12 Kyung-Hee KimEun Pyo HongYukyeong LeeZachariah L. McLeanEmanuela EleziRamee LeeSeung KwakBranduff McAllisterThomas H. MasseySergey LobanovPeter HolmansMichael OrthMarc CiosiDarren G. MoncktonJeffrey D. LongDiane LucenteVanessa C. WheelerMarcy E. MacDonaldJames F. GusellaJong-Min LeeaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114bDepartment of Neurology, Harvard Medical
Proceedings of the National Academy of Sciences, Volume 121, Issue 16, April 2024.
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Linking fine root lifespan to root chemical and morphological traits—A global analysis Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-12 Jiawen HouM. Luke McCormackPeter B. ReichTao SunRichard P. PhillipsHans LambersHan Y. H. ChenYiyang DingLouise H. ComasOscar J. Valverde-BarrantesEmily F. SollyGregoire T. FreschetaChinese Academy of Sciences Key Laboratory of Forest Ecology and Silviculture, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, ChinabCollege of Resources and Environment, University of Chinese
Proceedings of the National Academy of Sciences, Volume 121, Issue 16, April 2024.
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In This Issue Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16
Proceedings of the National Academy of Sciences, Volume 121, Issue 16, April 2024.
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Lipoarabinomannan modification as a source of phenotypic heterogeneity in host-adapted Mycobacterium abscessus isolates Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Kavita De, Juan M. Belardinelli, Arun Prasad Pandurangan, Teddy Ehianeta, Elena Lian, Zuzana Palčeková, Ha Lam, Mercedes Gonzalez-Juarrero, Josephine M. Bryant, Tom L. Blundell, Julian Parkhill, R. Andres Floto, Todd L. Lowary, William H. Wheat, Mary Jackson
Mycobacterium abscessus is increasingly recognized as the causative agent of chronic pulmonary infections in humans. One of the genes found to be under strong evolutionary pressure during adaptation of M. abscessus to the human lung is embC which encodes an arabinosyltransferase required for the biosynthesis of the cell envelope lipoglycan, lipoarabinomannan (LAM). To assess the impact of patient-derived
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Inferring COVID-19 testing and vaccination behavior from New Jersey testing data Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Ari S. Freedman, Justin K. Sheen, Stella Tsai, Jihong Yao, Edward Lifshitz, David Adinaro, Simon A. Levin, Bryan T. Grenfell, C. Jessica E. Metcalf
Characterizing the relationship between disease testing behaviors and infectious disease dynamics is of great importance for public health. Tests for both current and past infection can influence disease-related behaviors at the individual level, while population-level knowledge of an epidemic’s course may feed back to affect one’s likelihood of taking a test. The COVID-19 pandemic has generated testing
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The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Mekha A. Thomas, Pooja Naik, Hong Wang, Jon T. Giles, Alexander A. Girgis, Seok-Young Kim, Tory P. Johnson, Ashley M. Curran, Jonathan D. Crawford, Shaghayegh Jahanbani, Clifton O. Bingham, William H. Robinson, Chan Hyun Na, Erika Darrah
Although anti-citrullinated protein autoantibodies (ACPAs) are a hallmark serological feature of rheumatoid arthritis (RA), the mechanisms and cellular sources behind the generation of the RA citrullinome remain incompletely defined. Peptidylarginine deiminase IV (PAD4), one of the key enzymatic drivers of citrullination in the RA joint, is expressed by granulocytes and monocytes; however, the subcellular
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Live-attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Gang Chen, Qingxia Han, Wan-Xiang Li, Rong Hai, Shou-Wei Ding
Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor
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Neuromorphic one-shot learning utilizing a phase-transition material Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Alessandro R. Galloni, Yifan Yuan, Minning Zhu, Haoming Yu, Ravindra S. Bisht, Chung-Tse Michael Wu, Christine Grienberger, Shriram Ramanathan, Aaron D. Milstein
Design of hardware based on biological principles of neuronal computation and plasticity in the brain is a leading approach to realizing energy- and sample-efficient AI and learning machines. An important factor in selection of the hardware building blocks is the identification of candidate materials with physical properties suitable to emulate the large dynamic ranges and varied timescales of neuronal
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What one genus of showy moths can say about migration, adaptation, and wing pattern Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Jing Zhang, Qian Cong, Jinhui Shen, Leina Song, Winnie Hallwachs, Daniel H. Janzen, Andrei Sourakov, Nick V. Grishin
The Ornate Moth, Utetheisa ornatrix , has served as a model species in chemical ecology studies for decades. Like in the widely publicized stories of the Monarch and other milkweed butterflies, the Ornate Moth and its relatives are tropical insects colonizing whole continents assisted by their chemical defenses. With the recent advances in genomic techniques and evo-devo research, it is becoming a
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C-type inactivation and proton modulation mechanisms of the TASK3 channel Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Huajian Lin, Junnan Li, Qiansen Zhang, Huaiyu Yang, Shanshuang Chen
The TWIK-related acid-sensitive K + channel 3 (TASK3) belongs to the two-pore domain (K2P) potassium channel family, which regulates cell excitability by mediating a constitutive “leak” potassium efflux in the nervous system. Extracellular acidification inhibits TASK3 channel, but the molecular mechanism by which channel inactivation is coupled to pH decrease remains unclear. Here, we report the cryo-electron
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Unveiling synergy of strain and ligand effects in metallic aerogel for electrocatalytic polyethylene terephthalate upcycling Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Junliang Chen, Fangzhou Zhang, Min Kuang, Li Wang, Huaping Wang, Wei Li, Jianping Yang
Recently, there has been a notable surge in interest regarding reclaiming valuable chemicals from waste plastics. However, the energy-intensive conventional thermal catalysis does not align with the concept of sustainable development. Herein, we report a sustainable electrocatalytic approach allowing the selective synthesis of glycolic acid (GA) from waste polyethylene terephthalate (PET) over a Pd
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Substantial transmission of SARS-CoV-2 through casual contact in retail stores: Evidence from matched administrative microdata on card payments and testing Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Niels Johannesen, Alessandro Tang-Andersen Martinello, Bjørn Bjørnsson Meyer, Emil Toft Vestergaard, Asger Lau Andersen, Thais Lærkholm Jensen
This paper presents quasiexperimental evidence of Covid-19 transmission through casual contact between customers in retail stores. For a large sample of individuals in Denmark, we match card payment data, indicating exactly where and when each individual made purchases, with Covid-19 test data, indicating when each individual was tested and whether the test was positive. The resulting dataset identifies
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Spillover effects of reminder nudges in complex environments Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Alexander K. Koch, Dan Mønster, Julia Nafziger
We present an experiment on the immediate and lasting effects of reminder nudges in a complex environment. In the study, 1,542 subjects face a setting where, within a brief time frame, they have to pay attention to and perform multiple actions in a computer game. The experiment investigates i) the effect of reminders on the reminded actions and their spillovers on nonreminded actions; ii) spillovers
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The olivary input to the cerebellum dissociates sensory events from movement plans Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Jay S. Pi, Mohammad Amin Fakharian, Paul Hage, Ehsan Sedaghat-Nejad, Salomon Z. Muller, Reza Shadmehr
Neurons in the inferior olive are thought to anatomically organize the Purkinje cells (P-cells) of the cerebellum into computational modules, but what is computed by each module? Here, we designed a saccade task in marmosets that dissociated sensory events from motor events and then recorded the complex and simple spikes of hundreds of P-cells. We found that when a visual target was presented at a
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Regulation of the d-band center of metal–organic frameworks for energy-saving hydrogen generation coupled with selective glycerol oxidation Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Yuqian He, Zheng Ma, Feng Yan, Chunling Zhu, Tongyang Shen, Shulei Chou, Xiao Zhang, Yujin Chen
The hybrid electrolyzer coupled glycerol oxidation (GOR) with hydrogen evolution reaction (HER) is fascinating to simultaneously generate H 2 and high value-added chemicals with low energy input, yet facing a challenge. Herein, Cu-based metal–organic frameworks (Cu-MOFs) are reported as model catalysts for both HER and GOR through doping of atomically dispersed precious and nonprecious metals. Remarkably
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Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Lijie Gu, Yanhong Du, Jianglei Chen, Mohammad Nazmul Hasan, Yung Dai Clayton, David J. Matye, Jacob E. Friedman, Tiangang Li
Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined. Here, we report that hepatocyte Cul3 knockout results in rapid resolution of steatosis in obese mice
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Collective behavior from surprise minimization Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-17 Conor Heins, Beren Millidge, Lancelot Da Costa, Richard P. Mann, Karl J. Friston, Iain D. Couzin
Collective motion is ubiquitous in nature; groups of animals, such as fish, birds, and ungulates appear to move as a whole, exhibiting a rich behavioral repertoire that ranges from directed movement to milling to disordered swarming. Typically, such macroscopic patterns arise from decentralized, local interactions among constituent components (e.g., individual fish in a school). Preeminent models of
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Magnet-in-ferroelectric crystals exhibiting photomultiferroicity Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Zhongxuan Wang, Qian Wang, Weiyi Gong, Amy Chen, Abdullah Islam, Lina Quan, Taylor J. Woehl, Qimin Yan, Shenqiang Ren
Growing crystallographically incommensurate and dissimilar organic materials is fundamentally intriguing but challenging for the prominent cross-correlation phenomenon enabling unique magnetic, electronic, and optical functionalities. Here, we report the growth of molecular layered magnet-in-ferroelectric crystals, demonstrating photomanipulation of interfacial ferroic coupling. The heterocrystals
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Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Duc Minh Nguyen, Deanna H. Rath, Dominic Devost, Darlaine Pétrin, Robert Rizk, Alan X. Ji, Naveen Narayanan, Darren Yong, Andrew Zhai, Douglas A. Kuntz, Maha U. Q. Mian, Neil C. Pomroy, Alexander F. A. Keszei, Samir Benlekbir, Mohammad T. Mazhab-Jafari, John L. Rubinstein, Terence E. Hébert, Gilbert G. Privé
Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3 KCTD5 ) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5
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Differential nanoscale organization of excitatory synapses onto excitatory vs. inhibitory neurons Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Poorna A. Dharmasri, Aaron D. Levy, Thomas A. Blanpied
A key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters (NCs) whose precise alignment across the cleft in a transsynaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution
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Structural insights into the regulation of protein-arginine kinase McsB by McsA Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Md Arifuzzaman, Eunju Kwon, Dong Young Kim
In gram-positive bacteria, phosphorylated arginine functions as a protein degradation signal in a similar manner as ubiquitin in eukaryotes. The protein-arginine phosphorylation is mediated by the McsAB complex, where McsB possesses kinase activity and McsA modulates McsB activity. Although mcsA and mcsB are regulated within the same operon, the role of McsA in kinase activity has not yet been clarified
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Tight-packing of large pilin subunits provides distinct structural and mechanical properties for the Myxococcus xanthus type IVa pilus Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Anke Treuner-Lange, Weili Zheng, Albertus Viljoen, Steffi Lindow, Marco Herfurth, Yves F. Dufrêne, Lotte Søgaard-Andersen, Edward H. Egelman
Type IVa pili (T4aP) are ubiquitous cell surface filaments important for surface motility, adhesion to surfaces, DNA uptake, biofilm formation, and virulence. T4aP are built from thousands of copies of the major pilin subunit and tipped by a complex composed of minor pilins and in some systems also the PilY1 adhesin. While major pilins of structurally characterized T4aP have lengths of <165 residues
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Bmal1 integrates circadian function and temperature sensing in the suprachiasmatic nucleus Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Marieke M. B. Hoekstra, Natalie Ness, Aina Badia-Soteras, Marco Brancaccio
Circadian regulation and temperature dependency are important orchestrators of molecular pathways. How the integration between these two drivers is achieved, is not understood. We monitored circadian- and temperature-dependent effects on transcription dynamics of cold-response protein RNA Binding Motif 3 (Rbm3). Temperature changes in the mammalian master circadian pacemaker, the suprachiasmatic nucleus
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Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Stefania Bellone, Kyungjo Jeong, Mari Kyllesø Halle, Camilla Krakstad, Blair McNamara, Michelle Greenman, Levent Mutlu, Cem Demirkiran, Tobias Max Philipp Hartwich, Yang Yang-Hartwich, Margherita Zipponi, Natalia Buza, Pei Hui, Francesco Raspagliesi, Salvatore Lopez, Biagio Paolini, Massimo Milione, Emanuele Perrone, Giovanni Scambia, Gary Altwerger, Antonella Ravaggi, Eliana Bignotti, Gloria S. Huang
High-grade neuroendocrine cervical cancers (NETc) are exceedingly rare, highly aggressive tumors. We analyzed 64 NETc tumor samples by whole-exome sequencing (WES). Human papillomavirus DNA was detected in 65.6% (42/64) of the tumors. Recurrent mutations were identified in PIK3CA, KMT2D/MLL2, K-RAS, ARID1A, NOTCH2, and RPL10. The top mutated genes included RB1, ARID1A, PTEN, KMT2D / MLL2, and WDFY3
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Unveil the origin of voltage oscillation for sodium-ion batteries operating at −40 °C Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Lanfang Que, Fuda Yu, Jihuai Wu, Zhang Lan, Yutong Feng, Ruizheng Zhao, Zhihao Sun, Zhuo Yang, Hao Luo, Dongliang Chao
Voltage oscillation at subzero in sodium-ion batteries (SIBs) has been a common but overlooked scenario, almost yet to be understood. For example, the phenomenon seriously deteriorates the performance of Na 3 V 2 (PO 4 ) 3 (NVP) cathode in PC (propylene carbonate)/EC (ethylene carbonate)-based electrolyte at −20 °C. Here, the correlation between voltage oscillation, structural evolution, and electrolytes
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Milestoning estimators of dissipation in systems observed at a coarse resolution Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Kristian Blom, Kevin Song, Etienne Vouga, Aljaž Godec, Dmitrii E. Makarov
Many nonequilibrium, active processes are observed at a coarse-grained level, where different microscopic configurations are projected onto the same observable state. Such “lumped” observables display memory, and in many cases, the irreversible character of the underlying microscopic dynamics becomes blurred, e.g., when the projection hides dissipative cycles. As a result, the observations appear less
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The serine phosphorylations in the IRS-1 PIR domain abrogate IRS-1 and IR interaction Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Ju Rang Woo, Seung-Hyun Bae, Thomas E. Wales, John R. Engen, Jongsoon Lee, Hyonchol Jang, SangYoun Park
Serine phosphorylations on insulin receptor substrate 1 (IRS-1) by diverse kinases aoccur widely during obesity-, stress-, and inflammation-induced conditions in models of insulin resistance and type 2 diabetes. In this study, we define a region within the human IRS-1, which is directly C-terminal to the PTB domain encompassing numerous serine phosphorylation sites including Ser307 (mouse Ser302) and
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APOBEC2 safeguards skeletal muscle cell fate through binding chromatin and regulating transcription of non-muscle genes during myoblast differentiation Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 J. Paulo Lorenzo, Linda Molla, Elias Moris Amro, Ignacio L. Ibarra, Sandra Ruf, Cedrik Neber, Christos Gkougkousis, Jana Ridani, Poorani Ganesh Subramani, Jonathan Boulais, Dewi Harjanto, Alin Vonica, Javier M. Di Noia, Christoph Dieterich, Judith B. Zaugg, F. Nina Papavasiliou
The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide (APOBEC) family is composed of nucleic acid editors with roles ranging from antibody diversification to RNA editing. APOBEC2, a member of this family with an evolutionarily conserved nucleic acid–binding cytidine deaminase domain, has neither an established substrate nor function. Using a cellular model of muscle differentiation
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A frictional soliton controls the resistance law of shear-thickening suspensions in pipes Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Alexis Bougouin, Bloen Metzger, Yoël Forterre, Pascal Boustingorry, Henri Lhuissier
Pipe flows are commonly found in nature and industry as an effective mean of transporting fluids. They are primarily characterized by their resistance law, which relates the mean flow rate to the driving pressure gradient. Since Poiseuille and Hagen, various flow regimes and fluid rheologies have been investigated, but the behavior of shear-thickening suspensions, which jam above a critical shear stress
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Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Yan Q. Chen, Ye Yang, Eugene Y. Zhen, Thomas P. Beyer, Hongxia Li, Yi Wen, Mariam Ehsani, Nicholas Jackson, Katherine Xie, Hyesoo Jung, Julia L. Scheithauer, Anni Kumari, Gabriel Birrane, Anna M. Russell, Deepa Balasubramaniam, Zhongping Liao, Robert W. Siegel, Yuewei Qian, Michael Ploug, Stephen G. Young, Robert J. Konrad
Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue
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Observing heroic behavior and its influencing factors in immersive virtual environments Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Kelou Jin, Jie Wu, Ran Zhang, Shen Zhang, Xiaoyan Wu, Tingting Wu, Ruolei Gu, Chao Liu
Studying heroism in controlled settings presents challenges and ethical controversies due to its association with physical risk. Leveraging virtual reality (VR) technology, we conducted a three-study series with 397 participants from China to investigate heroic actions. Participants unexpectedly witnessed a criminal event in a simulated scenario, allowing observation of their tendency to physically
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Identification of an active RNAi pathway in Candida albicans Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-16 Elise Iracane, Cristina Arias-Sardá, Corinne Maufrais, Iuliana V. Ene, Christophe d’Enfert, Alessia Buscaino
RNA interference (RNAi) is a fundamental regulatory pathway with a wide range of functions, including regulation of gene expression and maintenance of genome stability. Although RNAi is widespread in the fungal kingdom, well-known species, such as the model yeast Saccharomyces cerevisiae , have lost the RNAi pathway. Until now evidence has been lacking for a fully functional RNAi pathway in Candida
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Brain-derived neurotrophic factor scales presynaptic calcium transients to modulate excitatory neurotransmission Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Camille S. Wang, Clara I. McCarthy, Natalie J. Guzikowski, Ege T. Kavalali, Lisa M. Monteggia
Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic physiology, as well as mechanisms underlying various neuropsychiatric diseases and their treatment. Despite its clear physiological role and disease relevance, BDNF’s function at the presynaptic terminal, a fundamental unit of neurotransmission, remains poorly understood. In this study, we evaluated single synapse dynamics using
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Refining greenhouse gas emission factors for Indonesian peatlands and mangroves to meet ambitious climate targets Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Daniel Murdiyarso, Erin Swails, Kristell Hergoualc’h, Rupesh Bhomia, Sigit D. Sasmito
For countries’ emission-reduction efforts under the Paris Agreement to be effective, baseline emission/removals levels and reporting must be as transparent and accurate as possible. For Indonesia, which holds among the largest area of tropical peatlands and mangrove forest in the world, it is particularly important for these high-carbon ecosystems to produce high-accuracy greenhouse gas inventory and
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Substrate geometry affects population dynamics in a bacterial biofilm Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Witold Postek, Klaudia Staśkiewicz, Elin Lilja, Bartłomiej Wacław
Biofilms inhabit a range of environments, such as dental plaques or soil micropores, often characterized by noneven surfaces. However, the impact of surface irregularities on the population dynamics of biofilms remains elusive, as most experiments are conducted on flat surfaces. Here, we show that the shape of the surface on which a biofilm grows influences genetic drift and selection within the biofilm
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How small changes to one eye’s retinal image can transform the perceived shape of a very familiar object Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Iona R. McLean, Ian M. Erkelens, Emily A. Cooper
Vision can provide useful cues about the geometric properties of an object, like its size, distance, pose, and shape. But how the brain merges these properties into a complete sensory representation of a three-dimensional object is poorly understood. To address this gap, we investigated a visual illusion in which humans misperceive the shape of an object due to a small change in one eye’s retinal image
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Reversal of C9orf72 mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Aradhana Sachdev, Kamaljot Gill, Maria Sckaff, Alisha M. Birk, Olubankole Aladesuyi Arogundade, Katherine A. Brown, Runvir S. Chouhan, Patrick Oliver Issagholian-Lewin, Esha Patel, Hannah L. Watry, Mylinh T. Bernardi, Kathleen C. Keough, Yu-Chih Tsai, Alec Simon Tulloch Smith, Bruce R. Conklin, Claire Dudley Clelland
Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient-derived induced pluripotent stem cell (iPSC) line and a non-diseased wild-type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal
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Coadaptation of coexisting plants enhances productivity in an agricultural system Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Anja Schmutz, Christian Schöb
Growing crops in more diverse crop systems (i.e., intercropping) is one way to produce food more sustainably. Even though intercropping, compared to average monocultures, is generally more productive, the full yield potential of intercropping might not yet have been achieved as modern crop cultivars are bred to be grown in monoculture. Breeding plants for more familiarity in mixtures, i.e., plants
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Proof-of-concept studies with a computationally designed M pro inhibitor as a synergistic combination regimen alternative to Paxlovid Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Christina Papini, Irfan Ullah, Amalendu P. Ranjan, Shuo Zhang, Qihao Wu, Krasimir A. Spasov, Chunhui Zhang, Walther Mothes, Jason M. Crawford, Brett D. Lindenbach, Pradeep D. Uchil, Priti Kumar, William L. Jorgensen, Karen S. Anderson
As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (M pro ) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir,
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Contribution of microscopy to a better understanding of the anatomy of pathogenic protists Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Wanderley de Souza
In this Inaugural Article the author briefly revises its scientific career and how he starts to work with parasitic protozoa. Emphasis is given to his contribution to topics such as a) the structural organization of the surface of protozoa using freeze-fracture and deep-etching; b) the cytoskeleton of protozoa, especially structures such as the subpellicular microtubules of trypanosomatids, the conoid
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Lecanemab blocks the effects of the Aβ/fibrinogen complex on blood clots and synapse toxicity in organotypic culture Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Pradeep Kumar Singh, Elisa Nicoloso Simões-Pires, Zu-Lin Chen, Daniel Torrente, Marissa Calvano, Anurag Sharma, Sidney Strickland, Erin H. Norris
Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer’s disease (AD). Vascular deficits include a compromised blood–brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen’s interaction with the amyloid-beta (Aβ) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab
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Balancing economic and ecological functions in smallholder and industrial oil palm plantations Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Arne Wenzel, Catrin Westphal, Johannes Ballauff, Dirk Berkelmann, Fabian Brambach, Damayanti Buchori, Nicolò Camarretta, Marife D. Corre, Rolf Daniel, Kevin Darras, Stefan Erasmi, Greta Formaglio, Dirk Hölscher, Najeeb Al-Amin Iddris, Bambang Irawan, Alexander Knohl, Martyna M. Kotowska, Valentyna Krashevska, Holger Kreft, Yeni Mulyani, Oliver Mußhoff, Gustavo B. Paterno, Andrea Polle, Anton Potapov
The expansion of the oil palm industry in Indonesia has improved livelihoods in rural communities, but comes at the cost of biodiversity and ecosystem degradation. Here, we investigated ways to balance ecological and economic outcomes of oil palm cultivation. We compared a wide range of production systems, including smallholder plantations, industrialized company estates, estates with improved agronomic
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Iron silicate perovskite and postperovskite in the deep lower mantle Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-04-15 Ziqiang Yang, Zijun Song, Zhongqing Wu, Ho-kwang Mao, Li Zhang
Ferromagnesian silicates are the dominant constituents of the Earth’s mantle, which comprise more than 80% of our planet by volume. To interpret the low shear-velocity anomalies in the lower mantle, we need to construct a reliable transformation diagram of ferromagnesian silicates over a wide pressure–temperature ( P-T ) range. While MgSiO 3 in the perovskite structure has been extensively studied