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Demographic models predict end-Pleistocene arrival and rapid expansion of pre-agropastoralist humans in Cyprus Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Corey J. A. Bradshaw, Christian Reepmeyer, Frédérik Saltré, Athos Agapiou, Vasiliki Kassianidou, Stella Demesticha, Zomenia Zomeni, Miltiadis Polidorou, Theodora Moutsiou
The antiquity of human dispersal into Mediterranean islands and ensuing coastal adaptation have remained largely unexplored due to the prevailing assumption that the sea was a barrier to movement and that islands were hostile environments to early hunter-gatherers [J. F. Cherry, T. P. Leppard, J. Isl. Coast. Archaeol. 13 , 191–205 (2018), 10.1080/15564894.2016.1276489 ]. Using the latest archaeological
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Hypothalamic vasopressin sex differentiation is observed by embryonic day 15 in mice and is disrupted by the xenoestrogen bisphenol A Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Jing Zheng, Dinara Baimoukhametova, Catherine Lebel, Jaideep S. Bains, Deborah M. Kurrasch
Arginine vasopressin (AVP) neurons of the hypothalamic paraventricular region (AVP PVN ) mediate sex-biased social behaviors across most species, including mammals. In mice, neural sex differences are thought to be established during a critical window around birth ( embryonic (E) day 18 to postnatal (P) day 2) whereby circulating testosterone from the fetal testis is converted to estrogen in sex-dimorphic
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Activity-driven chromatin organization during interphase: Compaction, segregation, and entanglement suppression Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Brian Chan, Michael Rubinstein
In mammalian cells, the cohesin protein complex is believed to translocate along chromatin during interphase to form dynamic loops through a process called active loop extrusion. Chromosome conformation capture and imaging experiments have suggested that chromatin adopts a compact structure with limited interpenetration between chromosomes and between chromosomal sections. We developed a theory demonstrating
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MACSPI enables tissue-selective proteomic and interactomic analyses in multicellular organisms Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Siyue Huang, Qiao Ran, Xiao-Meng Li, Xiucong Bao, Chaogu Zheng, Xiang David Li
Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method
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Foundations of reasoning with uncertainty via real-valued logics Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Ronald Fagin, Ryan Riegel, Alexander Gray
Interest in logics with some notion of real-valued truths has existed since at least Boole and has been increasing in AI due to the emergence of neuro-symbolic approaches, though often their logical inference capabilities are characterized only qualitatively. We provide foundations for establishing the correctness and power of such systems. We introduce a rich class of multidimensional sentences, with
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Macrophage transplantation rescues RNASET2-deficient leukodystrophy by replacing deficient microglia in a zebrafish model Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Holly A. Rutherford, Diogo Candeias, Christopher J. A. Duncan, Stephen A. Renshaw, Noémie Hamilton
RNASET2-deficient leukodystrophy is a rare infantile white matter disorder mimicking a viral infection and resulting in severe psychomotor impairments. Despite its severity, there is little understanding of cellular mechanisms of pathogenesis and no treatments. Recent research using the rnaset2 mutant zebrafish model has suggested that microglia may be the drivers of the neuropathology, due to their
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How total mRNA influences cell growth Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Ludovico Calabrese, Luca Ciandrini, Marco Cosentino Lagomarsino
Experimental observations tracing back to the 1960s imply that ribosome quantities play a prominent role in determining a cell’s growth. Nevertheless, in biologically relevant scenarios, growth can also be influenced by the levels of mRNA and RNA polymerase. Here, we construct a quantitative model of biosynthesis providing testable scenarios for these situations. The model explores a theoretically
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Peripheral preprocessing in Drosophila facilitates odor classification Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Palka Puri, Shiuan-Tze Wu, Chih-Ying Su, Johnatan Aljadeff
The mammalian brain implements sophisticated sensory processing algorithms along multilayered (“deep”) neural networks. Strategies that insects use to meet similar computational demands, while relying on smaller nervous systems with shallow architectures, remain elusive. Using Drosophila as a model, we uncover the algorithmic role of odor preprocessing by a shallow network of compartmentalized olfactory
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Large Fermi surface in pristine kagome metal CsV 3 Sb 5 and enhanced quasiparticle effective masses Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Wei Zhang, Tsz Fung Poon, Chun Wai Tsang, Wenyan Wang, X. Liu, J. Xie, S. T. Lam, Shanmin Wang, Kwing To Lai, A. Pourret, G. Seyfarth, G. Knebel, Wing Chi Yu, Swee K. Goh
The kagome metal CsV 3 Sb 5 is an ideal platform to study the interplay between topology and electron correlation. To understand the fermiology of CsV 3 Sb 5 , intensive quantum oscillation (QO) studies at ambient pressure have been conducted. However, due to the Fermi surface reconstruction by the complicated charge density wave (CDW) order, the QO spectrum is exceedingly complex, hindering a complete
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A hyperpolarizing neuron recruits undocked innexin hemichannels to transmit neural information in Caenorhabditis elegans Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Airi Nakayama, Masakatsu Watanabe, Riku Yamashiro, Hiroo Kuroyanagi, Hironori J. Matsuyama, Atsunori Oshima, Ikue Mori, Shunji Nakano
While depolarization of the neuronal membrane is known to evoke the neurotransmitter release from synaptic vesicles, hyperpolarization is regarded as a resting state of chemical neurotransmission. Here, we report that hyperpolarizing neurons can actively signal neural information by employing undocked hemichannels. We show that UNC-7, a member of the innexin family in Caenorhabditis elegans, functions
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Ultrapotent influenza hemagglutinin fusion inhibitors developed through SuFEx-enabled high-throughput medicinal chemistry Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Seiya Kitamura, Ting-Hui Lin, Chang-Chun David Lee, Akihiro Takamura, Rameshwar U. Kadam, Ding Zhang, Xueyong Zhu, Lucas Dada, Emiko Nagai, Wenli Yu, Yao Yao, K. Barry Sharpless, Ian A. Wilson, Dennis W. Wolan
Seasonal and pandemic-associated influenza strains cause highly contagious viral respiratory infections that can lead to severe illness and excess mortality. Here, we report on the optimization of our small-molecule inhibitor F0045(S) targeting the influenza hemagglutinin (HA) stem with our Sulfur-Fluoride Exchange (SuFEx) click chemistry–based high-throughput medicinal chemistry (HTMC) strategy. A
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Promoting sustainable smallholder farming via multistakeholder collaboration Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Zhichao An, Yi Yang, Xue Yang, Wenqi Ma, Wei Jiang, Yajuan Li, Guangfeng Chen, Weifeng Zhang, Minghao Zhuang, Chong Wang, Fusuo Zhang
Transforming smallholder farms is critical to global food security and environmental sustainability. The science and technology backyard (STB) platform has proved to be a viable approach in China. However, STB has traditionally focused on empowering smallholder farmers by transferring knowledge, and wide-scale adoption of more sustainable practices and technologies remains a challenge. Here, we report
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Deletion of TECRL promotes skeletal muscle repair by up-regulating EGR2 Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Sha Geng, Song-Bai Liu, Wei He, Xiangbin Pan, Yi Sun, Ting Xue, Shiyuan Han, Jing Lou, Ying Chang, Jiqing Zheng, Xinghong Shi, Yangxin Li, Yao-Hua Song
Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing
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Essential role of N-terminal SAM regions in STIM1 multimerization and function Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-16 Matthias Sallinger, Christina Humer, Hwei Ling Ong, Sasirekha Narayanasamy, Qi Tong Lin, Marc Fahrner, Herwig Grabmayr, Sascha Berlansky, Sean Choi, Tony Schmidt, Lena Maltan, Lara Atzgerstorfer, Martin Niederwieser, Irene Frischauf, Christoph Romanin, Peter B. Stathopulos, Indu Ambudkar, Romana Leitner, Daniel Bonhenry, Rainer Schindl
The single-pass transmembrane protein Stromal Interaction Molecule 1 (STIM1), located in the endoplasmic reticulum (ER) membrane, possesses two main functions: It senses the ER-Ca 2+ concentration and directly binds to the store-operated Ca 2+ channel Orai1 for its activation when Ca 2+ recedes. At high resting ER-Ca 2+ concentration, the ER-luminal STIM1 domain is kept monomeric but undergoes di/multimerization
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In This Issue Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14
Proceedings of the National Academy of Sciences, Volume 121, Issue 20, May 2024.
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YdbH and YnbE form an intermembrane bridge to maintain lipid homeostasis in the outer membrane of Escherichia coli Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Sujeet Kumar, Rebecca M. Davis, Natividad Ruiz
The outer membrane (OM) of didermic gram-negative bacteria is essential for growth, maintenance of cellular integrity, and innate resistance to many antimicrobials. Its asymmetric lipid distribution, with phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet, is required for these functions. Lpt proteins form a transenvelope bridge that transports newly synthesized LPS
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Three-component systems represent a common pathway for extracytoplasmic addition of pentofuranose sugars into bacterial glycans Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Steven D. Kelly, Nam Ha Duong, Jeremy T. Nothof, Todd L. Lowary, Chris Whitfield
Cell surface glycans are major drivers of antigenic diversity in bacteria. The biochemistry and molecular biology underpinning their synthesis are important in understanding host–pathogen interactions and for vaccine development with emerging chemoenzymatic and glycoengineering approaches. Structural diversity in glycostructures arises from the action of glycosyltransferases (GTs) that use an immense
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Misregulation of bromotyrosine compromises fertility in male Drosophila Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Qi Su, Bing Xu, Xin Chen, Steven E. Rokita
Biological regulation often depends on reversible reactions such as phosphorylation, acylation, methylation, and glycosylation, but rarely halogenation. A notable exception is the iodination and deiodination of thyroid hormones. Here, we report detection of bromotyrosine and its subsequent debromination during Drosophila spermatogenesis. Bromotyrosine is not evident when Drosophila express a native
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Neuronal PAS domain 1 identifies a major subpopulation of wakefulness-promoting GABAergic neurons in the basal forebrain Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Timothy A. Troppoli, Chun Yang, Fumi Katsuki, David S. Uygun, Ilyan Lin, David D. Aguilar, Tristan Spratt, Radhika Basheer, James M. McNally, C. Savio Chan, James T. McKenna, Ritchie E. Brown
Here, we describe a group of basal forebrain (BF) neurons expressing neuronal Per-Arnt-Sim (PAS) domain 1 (Npas1), a developmental transcription factor linked to neuropsychiatric disorders. Immunohistochemical staining in Npas1-cre-2A-TdTomato mice revealed BF Npas1 + neurons are distinct from well-studied parvalbumin or cholinergic neurons. Npas1 staining in GAD67-GFP knock-in mice confirmed that
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Declining Chinese attitudes toward the United States amid COVID-19 Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Yu Xie, Feng Yang, Junming Huang, Yuchen He, Yi Zhou, Yue Qian, Weicheng Cai, Jie Zhou
In this paper, we present findings from four separate studies using different data sources and methods to examine Chinese attitudes toward the United States amid the COVID-19 pandemic. The empirical results consistently indicate a marked and significant decline in Chinese attitudes toward the US between late 2019 and the end of 2022. Using a quasi-experimental design and granular survey data that exploit
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Wood-inspired anisotropic hydrogel electrolyte with large modulus and low tortuosity realizing durable dendrite-free zinc-ion batteries Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Jizhang Chen, Minfeng Chen, Hongli Chen, Ming Yang, Xiang Han, Dingtao Ma, Peixin Zhang, Ching-Ping Wong
While aqueous zinc-ion batteries exhibit great potential, their performance is impeded by zinc dendrites. Existing literature has proposed the use of hydrogel electrolytes to ameliorate this issue. Nevertheless, the mechanical attributes of hydrogel electrolytes, particularly their modulus, are suboptimal, primarily ascribed to the substantial water content. This drawback would severely restrict the
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Myxococcus xanthus encapsulin cargo protein EncD is a flavin-binding protein with ferric reductase activity Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Elif Eren, Norman R. Watts, James F. Conway, Paul T. Wingfield
Encapsulins are protein nanocompartments that regulate cellular metabolism in several bacteria and archaea. Myxococcus xanthus encapsulins protect the bacterial cells against oxidative stress by sequestering cytosolic iron. These encapsulins are formed by the shell protein EncA and three cargo proteins: EncB, EncC, and EncD. EncB and EncC form rotationally symmetric decamers with ferroxidase centers
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Chromatin regulates alternative polyadenylation via the RNA polymerase II elongation rate Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Joseph V. Geisberg, Zarmik Moqtaderi, Kevin Struhl
The RNA polymerase II (Pol II) elongation rate influences poly(A) site selection, with slow and fast Pol II derivatives causing upstream and downstream shifts, respectively, in poly(A) site utilization. In yeast, depletion of either of the histone chaperones FACT or Spt6 causes an upstream shift of poly(A) site use that strongly resembles the poly(A) profiles of slow Pol II mutant strains. Like slow
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Threshold current density for diffusion-controlled stability of electrolytic surface nanobubbles Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Yixin Zhang, Xiaojue Zhu, Jeffery A. Wood, Detlef Lohse
Understanding the stability mechanism of surface micro/nanobubbles adhered to gas-evolving electrodes is essential for improving the efficiency of water electrolysis, which is known to be hindered by the bubble coverage on electrodes. Using molecular simulations, the diffusion-controlled evolution of single electrolytic nanobubbles on wettability-patterned nanoelectrodes is investigated. These nanoelectrodes
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Design rules for controlling active topological defects Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Suraj Shankar, Luca V. D. Scharrer, Mark J. Bowick, M. Cristina Marchetti
Topological defects play a central role in the physics of many materials, including magnets, superconductors, and liquid crystals. In active fluids, defects become autonomous particles that spontaneously propel from internal active stresses and drive chaotic flows stirring the fluid. The intimate connection between defect textures and active flow suggests that properties of active materials can be
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Temperature compensation through kinetic regulation in biochemical oscillators Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Haochen Fu, Chenyi Fei, Qi Ouyang, Yuhai Tu
Nearly all circadian clocks maintain a period that is insensitive to temperature changes, a phenomenon known as temperature compensation (TC). Yet, it is unclear whether there is any common feature among different systems that exhibit TC. From a general timescale invariance, we show that TC relies on the existence of certain period-lengthening reactions wherein the period of the system increases strongly
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Synergistic induction of blood–brain barrier properties Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Gergő Porkoláb, Mária Mészáros, Anikó Szecskó, Judit P. Vigh, Fruzsina R. Walter, Ricardo Figueiredo, Ildikó Kálomista, Zsófia Hoyk, Gaszton Vizsnyiczai, Ilona Gróf, Jeng-Shiung Jan, Fabien Gosselet, Melinda K. Pirity, Monika Vastag, Natalie Hudson, Matthew Campbell, Szilvia Veszelka, Mária A. Deli
Blood–brain barrier (BBB) models derived from human stem cells are powerful tools to improve our understanding of cerebrovascular diseases and to facilitate drug development for the human brain. Yet providing stem cell–derived endothelial cells with the right signaling cues to acquire BBB characteristics while also retaining their vascular identity remains challenging. Here, we show that the simultaneous
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Mosaicism-independent mechanisms contribute to Pcdh19-related epilepsy and repetitive behaviors in Xenopus Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Jugeon Park, Eunee Lee, Chul Hoon Kim, Jiyeon Ohk, Hosung Jung
Protocadherin19 ( PCDH19 )-related epilepsy syndrome is a rare disorder characterized by early-onset epilepsy, intellectual disability, and autistic behaviors. PCDH19 is located on the X chromosome and encodes a calcium-dependent single-pass transmembrane protein, which regulates cell-to-cell adhesion through homophilic binding. In human, 90% of heterozygous females, containing PCDH19 wild-type and
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iATPSnFR2: A high-dynamic-range fluorescent sensor for monitoring intracellular ATP Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Jonathan S. Marvin, Alexandros C. Kokotos, Mukesh Kumar, Camila Pulido, Ariana N. Tkachuk, Jocelyn Shuxin Yao, Timothy A. Brown, Timothy A. Ryan
We developed a significantly improved genetically encoded quantitative adenosine triphosphate (ATP) sensor to provide real-time dynamics of ATP levels in subcellular compartments. iATPSnFR2 is a variant of iATPSnFR1, a previously developed sensor that has circularly permuted superfolder green fluorescent protein (GFP) inserted between the ATP-binding helices of the ε -subunit of a bacterial F 0 -F
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Interspecific transfer of genetic information through polyploid bridges Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Felipe Kauai, Quinten Bafort, Frederik Mortier, Marc Van Montagu, Dries Bonte, Yves Van de Peer
Hybridization blurs species boundaries and leads to intertwined lineages resulting in reticulate evolution. Polyploidy, the outcome of whole genome duplication (WGD), has more recently been implicated in promoting and facilitating hybridization between polyploid species, potentially leading to adaptive introgression. However, because polyploid lineages are usually ephemeral states in the evolutionary
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The effects of bathymetry on the long-term carbon cycle and CCD Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-15 Matthew Bogumil, Tushar Mittal, Carolina Lithgow-Bertelloni
The shape of the ocean floor (bathymetry) and the overlaying sediments provide the largest carbon sink throughout Earth’s history, supporting ~one to two orders of magnitude more carbon storage than the oceans and atmosphere combined. While accumulation and erosion of these sediments are bathymetry dependent (e.g., due to pressure, temperature, salinity, ion concentration, and available productivity)
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SRSF1 interactome determined by proximity labeling reveals direct interaction with spliceosomal RNA helicase DDX23 Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Danilo Segovia, Dexter W. Adams, Nickolas Hoffman, Polona Safaric Tepes, Tse-Luen Wee, Paolo Cifani, Leemor Joshua-Tor, Adrian R. Krainer
SRSF1 is the founding member of the SR protein family. It is required—interchangeably with other SR proteins—for pre-mRNA splicing in vitro, and it regulates various alternative splicing events. Dysregulation of SRSF1 expression contributes to cancer and other pathologies. Here, we characterized SRSF1’s interactome using proximity labeling and mass spectrometry. This approach yielded 190 proteins enriched
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Lipid-derived electrophiles inhibit the function of membrane channels during ferroptosis Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Antonius T. M. Van Kessel, Gonzalo Cosa
The therapeutic targeting of ferroptosis requires full understanding of the molecular mechanism of this regulated cell death pathway. While lipid-derived electrophiles (LDEs), including 4-hydroxy-2-nonenal (4-HNE), are important biomarkers of ferroptosis, a functional role for these highly reactive species in ferroptotic cell death execution has not been established. Here, through mechanistic characterization
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Requirements for the biogenesis of [2Fe-2S] proteins in the human and yeast cytosol Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Joseph J. Braymer, Oliver Stehling, Martin Stümpfig, Ralf Rösser, Farah Spantgar, Catharina M. Blinn, Ulrich Mühlenhoff, Antonio J. Pierik, Roland Lill
The biogenesis of iron–sulfur (Fe/S) proteins entails the synthesis and trafficking of Fe/S clusters, followed by their insertion into target apoproteins. In eukaryotes, the multiple steps of biogenesis are accomplished by complex protein machineries in both mitochondria and cytosol. The underlying biochemical pathways have been elucidated over the past decades, yet the mechanisms of cytosolic [2Fe-2S]
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Dichotomous dynamics of magnetic monopole fluids Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Chun-Chih Hsu, Hiroto Takahashi, Fabian Jerzembeck, Jahnatta Dasini, Chaia Carroll, Ritika Dusad, Jonathan Ward, Catherine Dawson, Sudarshan Sharma, Graeme M. Luke, Stephen J. Blundell, Claudio Castelnovo, Jonathan N. Hallén, Roderich Moessner, J. C. Séamus Davis
A recent advance in the study of emergent magnetic monopoles was the discovery that monopole motion is restricted to dynamical fractal trajectories [J. N. Hallén et al. , Science 378 , 1218 (2022)], thus explaining the characteristics of magnetic monopole noise spectra [R. Dusad et al., Nature 571 , 234 (2019); A. M. Samarakoon et al. , Proc. Natl. Acad. Sci. U.S.A. 119 , e2117453119 (2022)]. Here
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Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 John R. Ferrarone, Jerin Thomas, Arun M. Unni, Yuxiang Zheng, Michal J. Nagiec, Eric E. Gardner, Oksana Mashadova, Kate Li, Nikos Koundouros, Antonino Montalbano, Meer Mustafa, Lewis C. Cantley, John Blenis, Neville E. Sanjana, Harold Varmus
The tumor suppressor LKB1 is a serine/threonine protein kinase that is frequently mutated in human lung adenocarcinoma (LUAD). LKB1 regulates a complex signaling network that is known to control cell polarity and metabolism; however, the pathways that mediate the tumor-suppressive activity of LKB1 are incompletely defined. To identify mechanisms of LKB1-mediated growth suppression, we developed a spheroid-based
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A fungal protein organizes both glycogen and cell wall glucans Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Liza Loza, Tamara L. Doering
Glycogen is a glucose storage molecule composed of branched α-1,4-glucan chains, best known as an energy reserve that can be broken down to fuel central metabolism. Because fungal cells have a specialized need for glucose in building cell wall glucans, we investigated whether glycogen is used for this process. For these studies, we focused on the pathogenic yeast Cryptococcus neoformans , which causes
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Dark continuous noise from mutant G90D-rhodopsin predominantly underlies congenital stationary night blindness Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Zuying Chai, Yaqing Ye, Daniel Silverman, Kasey Rose, Alana Madura, Randall R. Reed, Jeannie Chen, King-Wai Yau
Congenital stationary night blindness (CSNB) is an inherited retinal disease that causes a profound loss of rod sensitivity without severe retinal degeneration. One well-studied rhodopsin point mutant, G90D-Rho, is thought to cause CSNB because of its constitutive activity in darkness causing rod desensitization. However, the nature of this constitutive activity and its precise molecular source have
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Bacterial lifestyle shapes pangenomes Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Anna E. Dewar, Chunhui Hao, Laurence J. Belcher, Melanie Ghoul, Stuart A. West
Pangenomes vary across bacteria. Some species have fluid pangenomes, with a high proportion of genes varying between individual genomes. Other species have less fluid pangenomes, with different genomes tending to contain the same genes. Two main hypotheses have been suggested to explain this variation: differences in species’ bacterial lifestyle and effective population size. However, previous studies
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Identification and characterization of a nonbiological small-molecular mimic of a Zika virus conformational neutralizing epitope Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Priscila M. S. Castanha, Patrick J. McEnaney, Yongseok Park, Anthea Bouwer, Elton J. F. Chaves, Roberto D. Lins, Nicholas G. Paciaroni, Paige Dickson, Graham Carlson, Marli T. Cordeiro, Tereza Magalhaes, Jodi Craigo, Ernesto T. A. Marques, Thomas Kodadek, Donald S. Burke
Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools and effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library of 508,032 synthetic, non-natural oligomers, we selected and characterized small molecules that mimic ZIKV epitopes. High-throughput fluorescence-activated cell sorter-based
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Microbes vary strategically in their metalation of mononuclear enzymes Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Sanjay Kumar Rohaun, Ramakrishnan Sethu, James A. Imlay
Studies have determined that nonredox enzymes that are cofactored with Fe(II) are the most oxidant-sensitive targets inside Escherichia coli . These enzymes use Fe(II) cofactors to bind and activate substrates. Because of their solvent exposure, the metal can be accessed and oxidized by reactive oxygen species, thereby inactivating the enzyme. Because these enzymes participate in key physiological
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ZEPPI: Proteome-scale sequence-based evaluation of protein–protein interaction models Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-14 Haiqing Zhao, Donald Petrey, Diana Murray, Barry Honig
We introduce ZEPPI (Z-score Evaluation of Protein–Protein Interfaces), a framework to evaluate structural models of a complex based on sequence coevolution and conservation involving residues in protein–protein interfaces. The ZEPPI score is calculated by comparing metrics for an interface to those obtained from randomly chosen residues. Since contacting residues are defined by the structural model
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The physical and evolutionary energy landscapes of devolved protein sequences corresponding to pseudogenes Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Hana Jaafari, Carlos Bueno, Nicholas P. Schafer, Jonathan Martin, Faruck Morcos, Peter G. Wolynes
Protein evolution is guided by structural, functional, and dynamical constraints ensuring organismal viability. Pseudogenes are genomic sequences identified in many eukaryotes that lack translational activity due to sequence degradation and thus over time have undergone “devolution.” Previously pseudogenized genes sometimes regain their protein-coding function, suggesting they may still encode robust
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Seabirds reveal mercury distribution across the North Atlantic Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Céline Albert, Børge Moe, Hallvard Strøm, David Grémillet, Maud Brault-Favrou, Arnaud Tarroux, Sébastien Descamps, Vegard Sandøy Bråthen, Benjamin Merkel, Jens Åström, Françoise Amélineau, Frédéric Angelier, Tycho Anker-Nilssen, Olivier Chastel, Signe Christensen-Dalsgaard, Johannis Danielsen, Kyle Elliott, Kjell Einar Erikstad, Alexey Ezhov, Per Fauchald, Geir W. Gabrielsen, Maria Gavrilo, Sveinn
Mercury (Hg) is a heterogeneously distributed toxicant affecting wildlife and human health. Yet, the spatial distribution of Hg remains poorly documented, especially in food webs, even though this knowledge is essential to assess large-scale risk of toxicity for the biota and human populations. Here, we used seabirds to assess, at an unprecedented population and geographic magnitude and high resolution
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Premeiotic 24-nt phasiRNAs are present in the Zea genus and unique in biogenesis mechanism and molecular function Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Junpeng Zhan, Sébastien Bélanger, Scott Lewis, Chong Teng, Madison McGregor, Aleksandra Beric, Michael A. Schon, Michael D. Nodine, Blake C. Meyers
Reproductive phasiRNAs (phased, small interfering RNAs) are broadly present in angiosperms and play crucial roles in sustaining male fertility. While the premeiotic 21-nt (nucleotides) phasiRNAs and meiotic 24-nt phasiRNA pathways have been extensively studied in maize ( Zea mays ) and rice ( Oryza sativa ), a third putative category of reproductive phasiRNAs–named premeiotic 24-nt phasiRNAs–have recently
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Mimicking natural deterrent strategies in plants using adhesive spheres Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Ralph van Zwieten, Thijs V. Bierman, Peter G. L. Klinkhamer, T. Martijn Bezemer, Klaas Vrieling, Thomas E. Kodger
With a continuous increase in world population and food production, chemical pesticide use is growing accordingly, yet unsustainably. As chemical pesticides are harmful to the environment and developmental resistance in pests is increasing, a sustainable and effective pesticide alternative is needed. Inspired by nature, we mimic one defense strategy of plants, glandular trichomes, to shift away from
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Southern Ocean drives multidecadal atmospheric CO 2 rise during Heinrich Stadials Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Kathleen A. Wendt, Christoph Nehrbass-Ahles, Kyle Niezgoda, David Noone, Michael Kalk, Laurie Menviel, Julia Gottschalk, James W. B. Rae, Jochen Schmitt, Hubertus Fischer, Thomas F. Stocker, Juan Muglia, David Ferreira, Shaun A. Marcott, Edward Brook, Christo Buizert
The last glacial period was punctuated by cold intervals in the North Atlantic region that culminated in extensive iceberg discharge events. These cold intervals, known as Heinrich Stadials, are associated with abrupt climate shifts worldwide. Here, we present CO 2 measurements from the West Antarctic Ice Sheet Divide ice core across Heinrich Stadials 2 to 5 at decadal-scale resolution. Our results
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Extreme elevational migration spurred cryptic speciation in giant hummingbirds Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Jessie L. Williamson, Ethan F. Gyllenhaal, Selina M. Bauernfeind, Emil Bautista, Matthew J. Baumann, Chauncey R. Gadek, Peter P. Marra, Natalia Ricote, Thomas Valqui, Francisco Bozinovic, Nadia D. Singh, Christopher C. Witt
The ecoevolutionary drivers of species niche expansion or contraction are critical for biodiversity but challenging to infer. Niche expansion may be promoted by local adaptation or constrained by physiological performance trade-offs. For birds, evolutionary shifts in migratory behavior permit the broadening of the climatic niche by expansion into varied, seasonal environments. Broader niches can be
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The GPAT4 / 6 / 8 clade functions in Arabidopsis root suberization nonredundantly with the GPAT5/7 clade required for suberin lamellae Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Kay Gully, Alice Berhin, Damien De Bellis, Cornelia Herrfurth, Ivo Feussner, Christiane Nawrath
Lipid polymers such as cutin and suberin strengthen the diffusion barrier properties of the cell wall in specific cell types and are essential for water relations, mineral nutrition, and stress protection in plants. Land plant–specific glycerol-3-phosphate acyltransferases (GPATs) of different clades are central players in cutin and suberin monomer biosynthesis. Here, we show that the GPAT4 / 6 / 8
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The 6-kilodalton peptide 1 in plant viruses of the family Potyviridae is a viroporin Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Mengzhu Chai, Lei Li, Yong Li, Yingshuai Yang, Yuting Wang, Xue Jiang, Yameng Luan, Fangfang Li, Hongguang Cui, Aiming Wang, Wensheng Xiang, Xiaoyun Wu, Xiaofei Cheng
Potyviridae, the largest family of plant RNA viruses, includes many important pathogens that significantly reduce the yields of many crops worldwide. In this study, we report that the 6-kilodalton peptide 1 (6K1), one of the least characterized potyviral proteins, is an endoplasmic reticulum–localized protein. AI–assisted structure modeling and biochemical assays suggest that 6K1 forms pentamers with
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Exploring the activation mechanism of metabotropic glutamate receptor 2 Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Xiaohong Zhu, Mengqi Luo, Ke An, Danfeng Shi, Tingjun Hou, Arieh Warshel, Chen Bai
Homomeric dimerization of metabotropic glutamate receptors (mGlus) is essential for the modulation of their functions and represents a promising avenue for the development of novel therapeutic approaches to address central nervous system diseases. Yet, the scarcity of detailed molecular and energetic data on mGlu2 impedes our in-depth comprehension of their activation process. Here, we employ computational
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Crop yields fail to rise in smallholder farming systems in sub-Saharan Africa Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Philip Wollburg, Thomas Bentze, Yuchen Lu, Christopher Udry, Douglas Gollin
Drawing on a harmonized longitudinal dataset covering more than 55,000 smallholder farms in six African countries, we analyze changes in crop productivity from 2008 to 2019. Because smallholder farmers represent a significant fraction of the world’s poorest people, agricultural productivity in this context matters for poverty reduction and for the broader achievement of the UN Sustainable Development
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Inflation in 2022 did not affect congressional voting, but abortion did Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Diana C. Mutz, Edward D. Mansfield
This study examines voting in the 2022 United States congressional elections, contests that were widely expected to produce a sizable defeat for Democratic candidates for largely economic reasons. Based on a representative national probability sample of voters interviewed in both 2020 and 2022, individuals who changed their vote from one party's congressional candidate to another party’s candidate
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The effects of Facebook and Instagram on the 2020 election: A deactivation experiment Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Hunt Allcott, Matthew Gentzkow, Winter Mason, Arjun Wilkins, Pablo Barberá, Taylor Brown, Juan Carlos Cisneros, Adriana Crespo-Tenorio, Drew Dimmery, Deen Freelon, Sandra González-Bailón, Andrew M. Guess, Young Mie Kim, David Lazer, Neil Malhotra, Devra Moehler, Sameer Nair-Desai, Houda Nait El Barj, Brendan Nyhan, Ana Carolina Paixao de Queiroz, Jennifer Pan, Jaime Settle, Emily Thorson, Rebekah Tromble
We study the effect of Facebook and Instagram access on political beliefs, attitudes, and behavior by randomizing a subset of 19,857 Facebook users and 15,585 Instagram users to deactivate their accounts for 6 wk before the 2020 U.S. election. We report four key findings. First, both Facebook and Instagram deactivation reduced an index of political participation (driven mainly by reduced participation
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Reduced stress propagation leads to increased mechanical failure resistance in auxetic materials Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Suzanne M. Fielding
Materials with a negative Poisson ratio have the counterintuitive property of expanding laterally when they are stretched longitudinally. They are accordingly termed auxetic, from the Greek auxesis meaning to increase. Experimental studies have demonstrated auxetic materials to have superior material properties, compared with conventional ones. These include synclastic curvature, increased acoustic
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The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Nelly Helmbrecht, Martin Lackner, Tomislav Maricic, Svante Pääbo
The aryl hydrocarbon receptor (AHR) is a transcription factor that has many functions in mammals. Its best known function is that it binds aromatic hydrocarbons and induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aromatic hydrocarbons and other substrates. All present-day humans carry an amino acid substitution at position 381 in the AHR that occurred after the
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PM 2.5 exposure contributes to anxiety and depression-like behaviors via phenyl-containing compounds interfering with dopamine receptor Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Shaoyang Ji, Yuqiong Guo, Wei Yan, Fang Wei, Jinjian Ding, Wenjun Hong, Xiaoyun Wu, Tingting Ku, Huifeng Yue, Nan Sang
As a global problem, fine particulate matter (PM 2.5 ) really needs local fixes. Considering the increasing epidemiological relevance to anxiety and depression but inconsistent toxicological results, the most important question is to clarify whether and how PM 2.5 causally contributes to these mental disorders and which components are the most dangerous for crucial mitigation in a particular place
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Real-time emulation of future global warming reveals realistic impacts on the phenological response and quality deterioration in rice Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Hironori Itoh, Hiroto Yamashita, Kaede C. Wada, Jun-ichi Yonemaru
Decreased production of crops due to climate change has been predicted scientifically. While climate-resilient crops are necessary to ensure food security and support sustainable agriculture, predicting crop growth under future global warming is challenging. Therefore, we aimed to assess the impact of realistic global warming conditions on rice cultivation. We developed a crop evaluation platform,
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Long-term declines in chlorophyll a and variable phenology revealed by a 60-year estuarine plankton time series Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Patricia S. Thibodeau, Gavino Puggioni, Jacob Strock, David G. Borkman, Tatiana A. Rynearson
Long-term ecological time series provide a unique perspective on the emergent properties of ecosystems. In aquatic systems, phytoplankton form the base of the food web and their biomass, measured as the concentration of the photosynthetic pigment chlorophyll a (chl a ), is an indicator of ecosystem quality. We analyzed temporal trends in chl a from the Long-Term Plankton Time Series in Narragansett
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Extreme shifts in pyrite sulfur isotope compositions reveal the path to bonanza gold Proc. Natl. Acad. Sci. U.S.A. (IF 11.1) Pub Date : 2024-05-13 Duncan F. McLeish, Anthony E. Williams-Jones, James R. Clark, Richard A. Stern
Pyrite is the most common sulfide mineral in hydrothermal ore-forming systems. The ubiquity and abundance of pyrite, combined with its ability to record and preserve a history of fluid evolution in crustal environments, make it an ideal mineral for studying the genesis of hydrothermal ore deposits, including those that host critical metals. However, with the exception of boiling, few studies have been