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

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• NRF2 is a spatiotemporal metabolic hub essential for the polyfunctionality of Th2 cells AI翻译
  作者：Choi, Garam; Ju, Hye-Yeon; Bok, Jahyun; Choi, Jungseo; Shin, Jae Woo; Oh, Hansol; Jeon, Yeojin; Kim, Jiyeon; Kim, Daehong; Moon, Heesu; Lee, Jeong-Eun; Keum, Young-Sam; Kim, You-Me; Kim, Hye Young; Park, Sung Ho; Han, Mi-Ryung; Chung, Yeonseok
  作者单位：Seoul National University (SNU); Incheon National University; Seoul National University (SNU); Ulsan National Institute of Science & Technology (UNIST); Dongguk University; Korea Advanced Institute of Science & Technology (KAIST)
  摘要：Upon encountering allergens, CD4 + T cells differentiate into IL- 4- producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL- 5 and IL- 13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune ...
• Stabilizing Ti 3 C 2 T x MXene flakes in air by removing confined water AI翻译
  作者：Fang, Hui; Thakur, Anupma; Zahmatkeshsaredorahi, Amirhossein; Fang, Zhenyao; Rad, Vahid; Shamsabadi, Ahmad A.; Pereyra, Claudia; Soroush, Masoud; Rappe, Andrew M.; Xu, Xiaoji G.; Anasori, Babak; Fakhraai, Zahra
  作者单位：University of Pennsylvania; Purdue University System; Purdue University; Purdue University System; Purdue University; Purdue University in Indianapolis; Indiana University System; Indiana University Indianapolis; Lehigh University; Drexel University; Purdue University System; Purdue University; Purdue University in Indianapolis
  摘要：MXenes have demonstrated potential for various applications owing to their tunable surface chemistry and metallic conductivity. However, high temperatures can accelerate MXene film oxidation in air. Understanding the mechanisms of MXene oxidation at elevated temperatures, which is still limited, is critical in improving their thermal stability for high-temperature applications. Here, we demonstrate that Ti3C2Tx MXene monoflakes have exceptional thermal stability at temperatures up to 600 degre...
• Plume-scale confinement on thermal convection AI翻译
  作者：Noto, Daisuke; Letelier, Juvenal A.; Ulloa, Hugo N.
  作者单位：University of Pennsylvania; Universidad de Chile
  摘要：Despite the ubiquity of thermal convection in nature and artificial systems, we still lack a unified formulation that integrates the system's geometry, fluid properties, and thermal forcing to characterize the transition from free to confined convective regimes. The latter is broadly relevant to understanding how convection transports energy and drives mixing across a wide range of environments, such as planetary atmospheres/oceans and hydrothermal flows through fractures, as well as engineeri...
• An RNA pseudoknot mediates toxin translation and antitoxin inhibition AI翻译
  作者：Eleftheraki, Athina; Holmqvist, Erik
  作者单位：Uppsala University; Uppsala University
  摘要：Type I toxin-antitoxin systems (T1TAs) are bipartite bacterial loci encoding a growth- inhibitory toxin and an antitoxin small RNA (sRNA). In many of these systems, the transcribed toxin mRNA is translationally inactive, but becomes translation- competent upon ribonucleolytic processing. The antitoxin sRNA targets the processed mRNA to inhibit its translation. This two-level control mechanism prevents cotranscriptional translation of the toxin and allows its synthesis only when the antitoxin i...
• Programming patchy particles for materials assembly design AI翻译
  作者：King, Ella M.; Du, Chrisy Xiyu; Zhu, Qian-Ze; Schoenholz, Samuel S.; Brenner, Michael P.
  作者单位：Harvard University; Harvard University; University of Hawaii System; University of Hawaii Manoa; Alphabet Inc.; Google Incorporated; OpenAI; University of Hawaii System; University of Hawaii Manoa
  摘要：Direct design of complex functional materials would revolutionize technologies ranging from printable organs to novel clean energy devices. However, even incremental steps toward designing functional materials have proven challenging. If the material is constructed from highly complex components, the design space of materials properties rapidly becomes too computationally expensive to search. On the other hand, very simple components such as uniform spherical particles are not powerful enough ...
• APACE: AlphaFold2 and advanced computing as a service for accelerated discovery in biophysics AI翻译
  作者：Park, Hyun; Patel, Parth; Haas, Roland; Levine, Herbert
  作者单位：United States Department of Energy (DOE); Argonne National Laboratory; University of Illinois System; University of Illinois Urbana-Champaign; University of Chicago; University of Illinois System; University of Illinois Urbana-Champaign
  摘要：The prediction of protein 3D structure from amino acid sequence is a computational grand challenge in biophysics and plays a key role in robust protein structure prediction algorithms, from drug discovery to genome interpretation. The advent of AI models, such as AlphaFold, is revolutionizing applications that depend on robust protein structure prediction algorithms. To maximize the impact, and ease the usability, of these AI tools we introduce APACE, AlphaFold2 and advanced computing as a ser...
• The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases AI翻译
  作者：Kim, Hyelim; Park, Hee Ho; Kim, Hong Nam; Seo, Donghyuk; Hong, Kyung Soo; Jang, Jong Geol; Seo, Eun U.; Kim, In- Young; Jeon, So- Young; Son, Boram; Cho, Seong-Woo; Kim, Wantae; Ahn, June Hong; Lee, Wonhwa
  作者单位：Korea Institute of Science & Technology (KIST); Yonsei University; Hanyang University; Hanyang University; Yonsei University; Yonsei University; Sungkyunkwan University (SKKU); Yeungnam University; Yeungnam University; University of Seoul
  摘要：Thymocyte selection-associated high - mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2) infection by binding to the cell surface receptor for advanced glycation end - products (RAGE). In various diseases, including COVID - 19, TO...
• The time course of person perception from voices in the brain AI翻译
  作者：Lavan, Nadine; Rinke, Paula; Scharinger, Mathias
  作者单位：University of London; Queen Mary University London; Philipps University Marburg; Philipps University Marburg
  摘要：When listeners hear a voice, they rapidly form a complex first impression of who the person behind that voice might be. We characterize how these multivariate first impressions from voices emerge over time across different levels of abstraction using electroencephalography and representational similarity analysis. We find that for eight perceived physical (gender, age, and health), trait (attractiveness, dominance, and trustworthiness), and social characteristics (educatedness and professional...
• A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes AI翻译
  作者：Smolko, Anne E.; Sullivan, Daniel W.; Olsen, Sarah Naomi; Kang, Hyuckjoon; Whedon, Samuel D.; Baell, Jonathan B.; Cole, Philip A.; Armstrong, Scott A.; Kuroda, Mitzi I.
  作者单位：Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Monash University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
  摘要：Aberrant regulation of chromatin modifiers is a common occurrence across many cancer types, and a key priority is to determine how specific alterations of these proteins, often enzymes, can be targeted therapeutically. MOZ, a histone acyltransferase, is recurrently fused to coactivators CBP, p300, and TIF2 in cases of acute myeloid leukemia (AML). Using either pharmacological inhibition or targeted protein degradation in a mouse model for MOZ - TIF2 - driven leukemia, we show that KAT6 (MOZ/MO...
• AMBRA1 levels predict resistance to MAPK inhibitors in melanoma AI翻译
  作者：Di Leo, Luca; Pagliuca, Chiara; Kishk, Ali; Rizza, Salvatore; Tsiavou, Christina; Pecorari, Chiara; Dahl, Christina; Pacheco, Maria Pires; Tholstrup, Rikke; Brewer, Jonathan Richard; Berico, Pietro; Hernando, Eva; Cecconi, Francesco; Ballotti, Robert; Bertolotto, Corine; Filomeni, Giuseppe; Gjerstorff, Morten Frier; Sauter, Thomas; Lovat, Penny; Guldberg, Per; De Zio, Daniela
  作者单位：University of Luxembourg; University of Southern Denmark; New York University; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; Universite Cote d'Azur; Universite Cote d'Azur; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Southern Denmark; University of Southern Denmark; Odense University Hospital; Newcastle University - UK
  摘要：Intrinsic and acquired resistance to mitogen - activated protein kinase inhibitors (MAPKi) in melanoma remains a major therapeutic challenge. Here, we show that the clinical development of resistance to MAPKi is associated with reduced tumor expression of the melanoma suppressor Autophagy and Beclin 1 Regulator 1 (AMBRA1) and that lower expression levels of AMBRA1 predict a poor response to MAPKi treatment. Functional analyses show that loss of AMBRA1 induces phenotype switching and orchestrat...