Proceedings of the National Academy of Sciences of the United States of America

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• Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH) AI翻译
  作者：Sundararamana, Sesh A.; Miller, Justin J.; Daleya, Ellora C.; O'Briena, Kelsey A.; Kasakc, Paulina; Danielsd, Abigail M.; Edwardse, Rachel L.; Heidelg, Kenneth M.; Bagueg, Darean A.; Wilsonh, Madeleine A.; Koelperh, Andrew J.; Kourtoglouh, Elexi C.; Whiteh, Alex D.; Augusth, Sloan A.; Appleh, Georgia A.; Rouambah, Regis W.; Durandh, Anthony J.; Estebh, John J.; Mulleri, Florian L.; Johnsonh, R. Jeremy; Hoopsh, Geoffrey C.; Dowdg, Cynthia S.; John, Audrey R. Odom
  作者单位：University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Thomas Jefferson University; University of Pennsylvania; Washington University (WUSTL); George Washington University; Butler University; University of Pennsylvania
  摘要：The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency ...
• Structural basis of DNA replication fidelity of the Mpox virus AI翻译
  作者：Xie, Yufeng; Kuai, Lu; Peng, Qi; Wang, Qian; Wang, Han; Li, Xiaomei; Qi, Jianxun; Ding, Qiang; Shi, Yi; Gao, George F.
  作者单位：Tsinghua University; Chinese Academy of Sciences; Institute of Microbiology, CAS; Peking University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Chinese Academy of Medical Sciences - Peking Union Medical College
  摘要：The Mpox virus (MPXV) is an orthopoxvirus that caused a global outbreak in 2022. The poxvirus DNA polymerase complex is responsible for the replication and integrity of the viral genome; however, the molecular mechanisms underlying DNA replication fidelity are still unclear. In this study, we determined the cryoelectron microscopy (cryo-EM) structures of the MPXV F8-A22-E4 polymerase holoenzyme in its editing state, in complex with mismatched primer-template DNA and DNA containing uracil deoxy...
• Evidence for a possible quantum effect on the formation of lithium-doped amorphous calcium phosphate from solution AI翻译
  作者：Straub, Joshua S.; Patel, Manisha L.; Nowotarski, Mesopotamia S.; Rao, Lokeswara; Turiansky, Mark E.; Fisher, Matthew P. A.; Helgeson, Matthew E.
  作者单位：University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara
  摘要：Differential isotope effects are an emerging tool for discovering possible nontrivial quantum mechanical effects within biological systems. However, it is often nearly impossible to elucidate the exact mechanisms by which a biological isotope effect manifests due to the complexity of these systems. As such, one proposed in vitro system of study for a quantum isotope effect is calcium phosphate aggregation, where symmetric calcium phosphate molecular species, known as Posner molecules, have bee...
• Functional mapping of the molluscan brain guided by synchrotron X- ray tomography AI翻译
  作者：Crossley, Michael; Simon, Anna; Marathe, Shashidhara; Rau, Christoph; Roth, Arnd; Marra, Vincenzo; Staras, Kevin
  作者单位：University of Sussex; University of London; University College London; Diamond Light Source
  摘要：Molluscan brains are composed of morphologically consistent and functionally interrogable neurons, offering rich opportunities for understanding how neural circuits drive behavior. Nonetheless, detailed component- level CNS maps are often lacking, total neuron numbers are unknown, and organizational principles remain poorly defined, limiting a full and systematic characterization of circuit operation. Here, we establish an accessible, generalizable approach, harnessing synchrotron X- ray tomog...
• Multiscale toughening mechanisms in biomimetic tendon- like hydrogels AI翻译
  作者：Guo, Xiao; Dong, Xinyu; Zou, Guijin; Zhang, Haoqi; Zeng, Kaiyang; Gao, Huajian; Zhai, Wei
  作者单位：National University of Singapore; Nanyang Technological University; Tsinghua University
  摘要：Mimicking hierarchical structures found in nature, such as nacre and tendon, has led to remarkable successes in the creation of biomimetic materials with exceptional properties. The depth of knowledge derived from nature extends far beyond mere trial- and- error fabrication by providing deep insights into the toughening mechanisms that are integral to natural materials. A key challenge is understanding how these toughening mechanisms can be effectively translated into biomimetic materials. Her...
• Ancient genomes reveal trans-Eurasian connections between the European Huns and the Xiongnu Empire AI翻译
  作者：Rusconea, Guido Alberto Gnecchi-; Racz, Zsofia; Liccardo, Salvatore; Lee, Juhyeon; Huang, Yilei; Traverso, Luca; Radzeviciute, Rita; Hajnal, Zsuzsanna; Szecsenyi-Nagy, Anna; Gyuris, Balazs; Mateovics-Laszlo, Orsolya; Bernert, Zsolt; Szeniczey, Tamas; Hajdu, Tamas; Meszaros, Boglarka; Balint, Marianna; Mende, Balazs Gusztav; Miller, Bryan; Samashev, Zainolla; Childebayeva, Ainash; Djansugurova, Leyla; Geary, Patrick; Ringbauer, Harald; Vida, Tivadar; Jeong, Choongwon; Pohl, Walter; Krause, Johannes; Hofmanova, Zuzana
  作者单位：Max Planck Society; Masaryk University; Eotvos Lorand University; University of Vienna; Austrian Academy of Sciences; Seoul National University (SNU); Seoul National University (SNU); Eotvos Lorand University; Eotvos Lorand University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Texas System; University of Texas Austin; Institute of Zoology in Kazakhstan; Institute for Advanced Study - USA
  摘要：The Huns appeared in Europe in the 370s, establishing an Empire that reshaped West Eurasian history. Yet until today their origins remain a matter of extensive debate. Traditional theories link them to the Xiongnu, the founders of the first nomadic empire of the Mongolian steppe. The Xiongnu empire dissolved, however, similar to 300 y before the Huns appeared in Europe, and there is little archaeological and historical evidence of Huns in the steppe during this time gap. Furthermore, despite t...
• Ethylene response factor SlERF.D6 promotes ripening in part through transcription factors SlDEAR2 and SlTCP12 AI翻译
  作者：Chen, Yao; Wang, Xin; Colantonio, Vincent; Gao, Zhuo; Pei, Yangang; Fish, Tara; Ye, Jie; Courtney, Lance; Thannhauser, Theodore W.; Ye, Zhibiao; Liu, Yongsheng; Fei, Zhangjun; Liu, Mingchun; Giovannoni, James J.
  作者单位：Cornell University; Boyce Thompson Institute for Plant Research; Sichuan University; Huazhong Agricultural University; Hubei Hongshan Laboratory; United States Department of Agriculture (USDA); Huazhong Agricultural University; Cornell University; Anhui Agricultural University
  摘要：Ripening is crucial for the development of fleshy fruits that release their seeds following consumption by frugivores and are important contributors to human health and nutritional security. Many genetic ripening regulators have been identified, especially in the model system tomato, yet more remain to be discovered and integrated into comprehensive regulatory models. Most tomato ripening genes have been studied in pericarp tissue, though recent evidence indicates that locule tissue is a site ...
• Wholesale flat subduction of the Indian slab and northward mantle convective flow: Plateau growth and driving force of the India-Asia collision AI翻译
  作者：Ma, Jincheng; Song, Xiaodong; Bunge, Hans-Peter; Fichtner, Andreas; Tian, You
  作者单位：Peking University; University of Munich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Jilin University
  摘要：The tectonic evolution of the Tibetan Plateau has been influenced by continental collision and postcollisional convergence of Indian and Eurasian plates, both of which have undoubtedly imposed their imprints on the lithosphere and upper-mantle structures beneath the collision zone. However, the mode by which the Indian Plate has subducted beneath Tibet, and its driving forces, have been highly uncertain. Here, we present seismic evidence from a full-waveform tomographic model that reveals flat...
• Raver1 links Ripk1 RNA splicing to caspase-8-mediated pyroptotic cell death, inflammation, and pathogen resistance AI翻译
  作者：Zhang, Boyao; Orning, Pontus; Lehman, Jesse W.; Dinis, Alexandre; Torres-Ulloa, Leslie; Elling, Roland; Kelliher, Michelle A.; Bertin, John; Proulx, Megan K.; Goguen, Jon D.; Ryan, Liv; Kandasamy, Richard K.; Espevik, Terje; Pai, Athma A.; Fitzgerald, Katherine A.; Lien, Egil
  作者单位：University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; Norwegian University of Science & Technology (NTNU); University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; University of Freiburg; University of Freiburg; University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; GlaxoSmithKline; Glaxosmithkline USA; Sanofi-Aventis; Sanofi USA; University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; Mayo Clinic; Norwegian University of Science & Technology (NTNU); University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School
  摘要：Multiple cell death and inflammatory signaling pathways converge on two critical factors: receptor- interacting serine/threonine kinase 1 (RIPK1) and caspase-8. Careful regulation of these molecules is critical to control apoptosis, pyroptosis, and inflammation. Here, we found a pivotal role of Raver1 as an essential regulator of Ripk1 pre-mRNA splicing, expression, and functionality and the subsequent caspase-8- dependent inflammatory cell death. We show that Raver1 influences mRNA diversity ...
• Contextual neural dynamics during time perception in the primate ventral premotor cortex AI翻译
  作者：Diaz, Hector; Bayones, Lucas; Alvarez, Manuel; Andrade-Ortega, Bernardo; Valero, Sebastian; Zainos, Antonio; Romo, Ranulfo; Rossi-Pool, Roman
  作者单位：Universidad Nacional Autonoma de Mexico; Universidad Nacional Autonoma de Mexico
  摘要：Understanding how time perception adapts to cognitive demands remains a significant challenge. In some contexts, the brain encodes time categorically (as long or short), while in others, it encodes precise time intervals on a continuous scale. Although the ventral premotor cortex (VPC) is known for its role in complex temporal processes, such as speech, its specific involvement in time estimation remains underexplored. In this study, we investigated how the VPC processes temporal information d...