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作者：Jin, Jiacheng; Zhang, Ruohan; Li, Jianying; Gao, Fengxia; Liao, Zhiwei; Yu, Yanbao; Wang, Yi; Bucci, Donna; Xiao, Min; Ma, Ruilin; Ma, Qin; Gao, Shuaixin; Lio, Jerry; Novais, Fernanda; Huang, Stanley Ching- Cheng; Zhu, Jiangjiang; Ghoneim, Hazem; Wen, Haitao; Li, Zihai; Sun, Nuo; Xin, Gang
作者单位：University System of Ohio; James Cancer Hospital & Solove Research Institute; Ohio State University; University System of Ohio; James Cancer Hospital & Solove Research Institute; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University of Delaware; New York University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University
摘要：Optimal activation of CD8+ T cells is crucial for immunity-mediated destruction of cancer, requiring a substantial amount of proteins involved in metabolism, proliferation, and effector function. Despite extensive studies emphasizing the role of transcriptional regulation in this process, paired transcriptomic and proteomic analyses reveal that the RNA profile is poorly correlated with protein levels. This discrepancy underscores the importance of post-translational modifications (PTMs) in con...
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作者：Kabinger, Florian; Doze, Valerie; Schmitzova, Jana; Lidschreiber, Michael; Dienemann, Christian; Cramer, Patrick
摘要：Targeting the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with small molecules is a promising therapeutic strategy against COVID-19, but potent and safe inhibitors are lacking. HeE1-2Tyr, a nonnucleoside inhibitor of Dengue virus RdRp, was also shown to inhibit SARS-CoV-2 RdRp in vitro and to have antiviral activity in cells, but the underlying mechanism remains unclear. Here, we elucidate the molecular mechanism of HeE1-2Tyr-mediated SARS-CoV-2 RdRp inhibition. Biochemical assays confir...
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作者：Scherrer, Simon; Ramakrishna, Shivaprakash N.; Niggel, Vincent; Hsu, Chiao-Peng; Style, Robert W.; Spencer, Nicholas D.; Isa, Lucio
作者单位：Swiss Federal Institutes of Technology Domain; ETH Zurich; Technical University of Munich
摘要：Contacts between particles in dense, sheared suspensions are believed to underpin much of their rheology. Roughness and adhesion are known to constrain the relative motion of particles, and thus globally affect the shear response, but an experimental description of how they microscopically influence the transmission of forces and relative displacements within contacts is lacking. Here, we show that an innovative colloidal-probe atomic force microscopy technique allows the simultaneous measurem...
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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; Pennsylvania Medicine; Thomas Jefferson University; University of Pennsylvania; Washington University (WUSTL); George Washington University; Butler University; University of Pennsylvania; Pennsylvania Medicine
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 ...
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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; Beijing Life Science Academy; 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...
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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...
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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...
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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...
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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...
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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; Hubei Hongshan Laboratory; Huazhong Agricultural University; 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 ...
