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作者:Chen, Li; Zhou, Xujiao; Huang, Chengsi; Zhang, Yirou; Xin, Changchang; Hong, Jiaxu; Wang, Yu
作者单位:Shenzhen University; Shenzhen University; Fudan University; Fudan University; Fudan University; Chinese Academy of Sciences; Shenzhen Institute of Advanced Technology, CAS
摘要:Compact programmable nucleases provide versatile genome editing tools with therapeutic potential, particularly when delivered via adeno-associated virus (AAV) vectors. However, their limited editing efficacy and stringent protospaceradjacent motif (PAM) requirements impose significant limitations in practical application. Here, we engineered MiniCasUltra, an optimized Un1Cas12f1 variant, through rational minimal off-target effects (on/off-target ratio > 10), and an expanded PAM preference (5 '...
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作者:Tan, Ee Phie; Lyang, Nora; Doroodian, Saam; Sanz-Martinez, Pablo; Xu, Jin; Zaretski, Sviatlana; Nieto-Torres, Jose L.; Ebata, Hiroshi; Lim, Shaun H. Y.; Hou, William C.; Clay, Khalyd J.; Yoon, Leonard; Rhoades, Derek; Garza, Danny; Johnson, Kristen A.; To, Alan; Ambaye, Lydia; Bentley, Emily P.; Petrascheck, Michael; Stolz, Alexandra; Kelly, Jeffery W.; Hansen, Malene
作者单位:Universidad CEU Cardenal Herrera; Sanford Burnham Prebys Medical Discovery Institute; Scripps Research Institute; Buck Institute for Research on Aging; Goethe University Frankfurt; Goethe University Frankfurt; Scripps Research Institute; Scripps Research Institute; Scripps Research Institute; Scripps Research Institute
摘要:The degradation of cellular components through autophagy is essential for longevity and healthy aging. However, autophagy function decreases with aging, contributing to age-related diseases. In this study, we characterized a small-molecule activator of autophagy called AA-20 that enhances autophagy and lipid droplet clearance in human cells and in the nematode Caenorhabditis elegans. AA-20 reduces polyglutamine aggregation in an autophagy-dependent manner in both human cells and C. elegans, wh...
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作者:Chen, Haopeng; Verbeke, Pieter; Mattioni, Stefania; Calderon, Cristian Buc; Verguts, Tom
作者单位:Ghent University; HOWEST University of Applied Sciences
摘要:Testing enhances memory more than studying. Although numerous studies have demonstrated the robustness of this classic effect, its neural and computational origin remains debated. Predictive learning is a potential mechanism behind this phenomenon: Because predictions and prediction errors (mismatch between predictions and feedback) are more likely to be generated in testing (relative to in studying), testing can benefit more from predictive learning. We shed light on the testing effect from a...
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作者:Ferguson, Shawn M.
作者单位:Yale University; Yale University
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作者:He, Yucheng; Huang, Yan; Xiao, Hengyu; Jiang, Jun; Wang, Song
作者单位:Chinese Academy of Sciences; University of Science & Technology of China, CAS
摘要:Identifying reaction intermediates is a critical component of elucidating the mechanisms of chemical reactions. Spectroscopic techniques are instrumental in this identification process. The capacity of AI to establish the correlations between spectra and chemical substances renders it a suitable tool for spectra analysis. However, the presence of limited data, or even the absence of data, is a common occurrence for intermediates with transient characteristics. This poses a significant challeng...
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作者:Xu, Xi; V. Zuza, Andrew; Liu, Lijun; Zhu, Weilin; Sun, Yanyun; Wang, Baodi; Kuang, Xingtao; Han, Song; Zhang, Xuanjie; Zhang, Wan; Fu, Xiaowei; Pearson, D. Graham; Liu, Jingao
作者单位:Yangtze University; Yangtze University; China Geological Survey; Tongji University; Nevada System of Higher Education (NSHE); University of Nevada Reno; Chinese Academy of Sciences; Institute of Geology & Geophysics, CAS; China National Offshore Oil Corporation (CNOOC); University of Alberta; China University of Geosciences; China University of Geosciences
摘要:The evolution of continents is shaped by the growth and destruction of long-lived cratons, which serve as their stable cores. Processes for craton destruction are controversial because most invoked mechanisms occur frequently throughout Earth history, making the preservation of cratons for billions of years problematic. Here, we address this issue by presenting a crustal-scale analytical signal-amplitude model obtained from high-resolution airborne and shipborne magnetic data across cratons wi...
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作者:Zhou, Nan; Zhang, Yan; Chen, Peng R.; Fan, Xinyuan
作者单位:Peking University; Peking University
摘要:Apoptosis is a critical outcome of stress-induced processes, with the endoplasmic reticulum (ER) playing a central role in apoptotic protein processing and stress signal transduction. Profiling the ER proteome during stress to cell death offers valuable insights into these processes, but existing methods often suffer from a loss of in situ information or requirement of genetic manipulation. In this study, we introduce CAT-ER, a nongenetic ER proteomics system that provides in situ labeling, sp...
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作者:Junod, Samuel L.; Rush, Coby; Tingey, Mark; Yang, Weidong
作者单位:Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University
摘要:Efficient gene expression depends on the tightly regulated export of messenger RNA (mRNA) through nuclear pore complexes (NPCs), which are densely modified by O-linked N-acetylglucosamine (O-GlcNAc). Although dysregulated O-GlcNAcylation has been linked to a variety of human diseases, the precise distribution of O-GlcNAc within the NPC and its effects on mRNA export remain poorly understood. Here, we combined single-point edge-excitation subdiffraction (SPEED) microscopy with stochastic optica...
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作者:Latawiec, Elisabeth I.; Chiesa, Alessandro; Qiu, Yunfan; Tcyrulnikov, Nikolai A.; Young, Ryan M.; Carretta, Stefano; Krzyaniak, Matthew D.; Wasielewski, Michael R.
作者单位:Northwestern University; Northwestern University; University of Parma; University of Parma; Consiglio Nazionale delle Ricerche (CNR); Istituto di Scienze e Tecnologie Molecolari (ISTM-CNR); Istituto Nazionale di Fisica Nucleare (INFN)
摘要:Chirality-induced spin selectivity (CISS) results in spin polarization of electrons transmitted through chiral molecules and materials. Since CISS results in spin polarization even at room temperature, it affords the possibility of using it to develop quantum technologies that can operate under ambient conditions. We have shown previously that photo-driven hole transfer within DNA hairpins provides a facile route to generate spin-correlated radical pairs (SCRPs). To study the effect of CISS on...
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作者:McGuire, Donald J.; Akondy, Rama S.; Yang, Shu; Edupuganti, Srilatha; Nagar, Shashi; Michael, Garett; Rosa, Stephen C. De; Newell, Evan W.; Farber, Donna L.; Kissick, Haydn T.; McElrath, M. Juliana; Ahmed, Rafi
作者单位:Emory University; Emory University; Ashoka University; Tianjin Medical University; Tianjin Medical University; ICON plc; Fred Hutchinson Cancer Center; Columbia University; NewYork-Presbyterian Hospital; NewYork-Presbyterian Hospital; Columbia University; Emory University
摘要:This study examines the expression of CD45 isoforms on human yellow fever virus vaccine (YFV-17D) specific CD8 T cells longitudinally after vaccination. As expected, effector CD8 T cells at day 14 express CD45RO but within 4 to 6 wk these virus-specific CD8 T cells become CD45RA positive and remain CD45RA for >10 y. The journey for these YFV-specific CD8 T cells goes from naive (CD45RA+ CCR7+) to effector/ effector memory (CD45RO+ CCR7-) to Temra (CD45RA+ CCR7-) to stem-cell memory (CD45RA+ CC...