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

最新文章

• Multiarea processing in body patches of the primate inferotemporal cortex implements inverse graphics AI翻译
  作者：Yilmaz, Hakan; Shah, Aalap D.; Letrou, Ariadne; Kumar, Satwant; Vogels, Rufin; Yildirim, Ilker
  作者单位：Yale University; Princeton University; KU Leuven; KU Leuven; Yale University; Yale University; Yale University
  摘要：Stimulus-driven, multiarea processing in the inferotemporal (IT) cortex is thought to be critical for transforming sensory inputs into useful representations of the world. What are the formats of these neural representations and how are they computed across the nodes of the IT networks? A growing literature in computational neuroscience focuses on the computational-level objective of acquiring high-level image statistics that supports useful distinctions, including between object identities or...
• Total synthesis and biological activity of carbamorphine: O-to-CH2 replacement in the E-ring of the morphine core structure AI翻译
  作者：Akiyama, Sota; Ople, Rohini S.; Kremsmair, Alexander; Ramos-Gonzalez, Nokomis; Nedungadan, Thomas; Kennedy, Brandon J.; Appourchaux, Kevin; Eans, Shainnel O.; Tsai, Bowen A.; Kraml, Christina; Huang, Xi-Ping; McLaughlin, Jay P.; Majumdar, Susruta; Sarpong, Richmond
  作者单位：University of California System; University of California Berkeley; Washington University (WUSTL); Washington University (WUSTL); University of Health Sciences & Pharmacy in St. Louis; Princeton University; State University System of Florida; University of Florida; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
  摘要：Morphine is a mu- opioid receptor (MOR) agonist and potent analgesic. However, it displays several side effects including respiratory depression and addiction. Here, we show that a single heavy atom replacement in the morphine core structure (O to CH2 exchange in the E-ring) prepared through a 15-step total synthesis displays a different pharmacological profile. The total synthesis features an intramolecular inverse electron-demand Diels-Alder cycloaddition and a stereoselective Giese radical ...
• Fundamental toughening landscape in soft-hard composites: Insights from a minimal framework AI翻译
  作者：Tian, Fucheng; Sato, Katsuhiko; Zheng, Yong; Lu, Feixue; Gong, Jian Ping
  作者单位：Hokkaido University; University of Toyama; Xi'an Jiaotong University; Hokkaido University
  摘要：Soft-hard composite strategy is a highly general yet powerful approach to overcome the inherent trade-off between strength and toughness in material design. However, the underlying toughening mechanisms, veiled by nonlinearities and complex network interactions, remains unclear. Here, we employ a three-dimensional soft-hard composite (SH-com) framework by arranging randomly distributed linear-elastic soft and hard elements to explore the toughening mechanisms of soft-hard composites, while shi...
• Reply to Izuma and Kakinuma: Conversation aligns self-views above and beyond noise reduction AI翻译
  作者：Welker, Christopher; Wheatley, Thalia; Meyer, Meghan
  作者单位：Dartmouth College; The Santa Fe Institute; Columbia University
• Structural state governs the mechanism of shear- band propagation in metallic glasses AI翻译
  作者：Yu, Jinhua; Zhang, Zhen; Sha, Zhendong; Ding, Jun; Greer, A. Lindsay; Ma, Evan
  作者单位：Xi'an Jiaotong University; Chengdu University of Technology; Xi'an Jiaotong University; University of Cambridge; Tohoku University
  摘要：Shear bands (SBs) play a critical role in determining the mechanical behavior of metallic glasses (MGs). However, the rapid dynamics and highly localized nature of SB propagation present significant challenges for direct observation of their atomistic mechanisms using experimental techniques. In this study, we employ hybrid molecular dynamics/Monte Carlo simulations to investigate the atomic-scale mechanisms of SB propagation in Mg65Cu25Y10 MGs, prepared using cooling rates as slow as 10(4) K ...
• UFMylation: A supervisor of the HIF1α pathway and a potential therapeutic target for anti- PD-1 combination therapy in hypoxic tumors AI翻译
  作者：Zou, Yongkang; Wang, Zhaoxiang; Jiang, Qiang; Kong, Xia; Ma, Xiaohe; Liang, Zhengyan; Wang, Zhiguo; Chen, Beiying; Yuan, Jiao; Wen, Jiayue; Ye, Sheng; Yan, Yubin; Li, Binbin; Xiong, Xing-dong; Liu, Xin-guang; He, Zhiwei; Cai, Yafei; Zhou, Junzhi
  作者单位：Shenzhen Bay Laboratory; Guangdong Medical University; Nanjing Agricultural University; Shandong Academy of Agricultural Sciences; Hangzhou Normal University; Guangzhou Medical University; Guangzhou Laboratory; Chinese Academy of Sciences; Guangzhou Institute of Biomedicine & Health, CAS
  摘要：Activation of hypoxia signaling has been identified as an innate resistance signature against anti- PD- 1 therapy, suggesting its potential as a target for combination treatments. Here, we demonstrate that UFMylation modification of HIF1 alpha stabilizes the protein by antagonizing its ubiquitination and proteasomal degradation under hypoxic conditions. Mechanistically, depletion of UFL1 or defective UFMylation increases HIF1 alpha binding to p53, promoting its degradation. Depletion of UFL1 o...
• Genome- scale knockout simulation and clustering analysis of drug- resistant breast cancer cells reveal drug sensitization targets AI翻译
  作者：Lim, Jina; Jung, Hae Deok; Park, Soo Young; Jeon, Moonhyeon; Kim, Da Sol; Cho, Ryeongeun; Han, Dohyun; Ryu, Han Suk; Kim, Yoosik; Kim, Hyun Uk
  作者单位：Korea Advanced Institute of Science & Technology (KAIST); Seoul National University (SNU); Seoul National University Hospital; Seoul National University (SNU); Seoul National University Hospital; Seoul National University (SNU); Seoul National University Hospital; Seoul National University (SNU); Seoul National University (SNU); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST)
  摘要：Anticancer chemotherapy is an essential part of cancer treatment, but the emergence of resistance remains a major hurdle. Metabolic reprogramming is a notable phenotype associated with the acquisition of drug resistance. Here, we develop a computational framework that predicts metabolic gene targets capable of reverting the metabolic state of drug-resistant cells to that of drug-sensitive parental cells, thereby sensitizing the resistant cells. The computational framework performs single-gene ...
• Immune cell profiling reveals diverse niches of immune residents of the enteric nervous system and potential neuroimmune interactions AI翻译
  作者：Wang, Haozhe; Zaini, Aidil; Cardwell, Bailey; Rowe, Matthew C.; Butler, Alana; Wong, Connie H. Y.; Poole, Daniel P.; Marsland, Benjamin; Bornstein, Joel C.; Harris, Nicola L.
  作者单位：Monash University; Monash University; Monash University; University of Melbourne
  摘要：Gastrointestinal (GI) neuroimmune interactions are crucial sensors and regulators of tissue homeostasis. Most enteric neurons reside within the myenteric plexus of the enteric nervous system in the muscular region, forming a structure called the muscularis externa. Despite established interactions between muscularis macrophages and neurons, the presence and function of other immune cell types remains poorly characterized. Here, we mapped the muscularis immune cell landscape, revealing that div...
• Genetic ancestry shapes dengue virus infection in human skin explants AI翻译
  作者：Castanha, Priscila M. S.; Marti, Michelle M.; Duangkhae, Parichat; Taddonio, Jocelyn M.; Cooper, Kristine L.; Wallace, Megan; Kettenburg, Gwenddolen; Erdos, Geza; Chavva, Hasitha; Alex, Aleena; Rubin, J. Peter; Watkins, Simon C.; Falo Jr, Louis D.; Marques, Ernesto T. A.; Martinson, Jeremy J.; Boyes, Simon M. Barratt -
  作者单位：University of Chicago; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Fundacao Oswaldo Cruz
  摘要：Dengue is the most prevalent arthropod-borne viral disease of humans, with over half the world's population at risk. Infection with any of the four dengue virus (DENY) serotypes is most often self-limiting, but a significant number of cases present with severe dengue characterized by vascular leakage that may be fatal. African ancestry is associated with protection against severe dengue, but the mechanisms are unknown. Using skin explants from genetically defined donors, we show that European ...
• Parental mixed-gender preferences revealed by IVF twin births AI翻译
  作者：Chu, C. Y. Cyrus; Lin, Chang-Ching; Lu, Shih -Ting; Kao, Ching- Yuan
  作者单位：Academia Sinica - Taiwan; National Taiwan University
  摘要：In vitro fertilization (IVF) affects human fertility by 1) increasing the probability of multiple births through the transfer of multiple embryos, 2) raising the proportion of dizygotic twins, which leads to a higher occurrence of one-boy-one-girl twins, and 3) enabling gender selection through preimplantation genetic screening (PGS) when parents have specific gender preferences. While the above-mentioned increase in multiple births is well documented, the impact on the twins' gender compositi...