High-resolution functional mapping of RAD51C by saturation genome editing [0.03%]
饱和基因组编辑的RAD51C高分辨率功能图谱绘制
Rebeca Olvera-León,Fang Zhang,Victoria Offord et al.
Rebeca Olvera-León et al.
Pathogenic variants in RAD51C confer an elevated risk of breast and ovarian cancer, while individuals homozygous for specific RAD51C alleles may develop Fanconi anemia. Using saturation genome editing (SGE), we functionally assess 9,188 uni...
In vivo DNA replication dynamics unveil aging-dependent replication stress [0.03%]
体内DNA复制动力学揭示了与衰老相关的复制压力
Giacomo G Rossetti,Noëlle Dommann,Angeliki Karamichali et al.
Giacomo G Rossetti et al.
The genome duplication program is affected by multiple factors in vivo, including developmental cues, genotoxic stress, and aging. Here, we monitored DNA replication initiation dynamics in regenerating livers of young and old mice after par...
Helen H Yang,Bella E Brezovec,Laia Serratosa Capdevila et al.
Helen H Yang et al.
Locomotion involves rhythmic limb movement patterns that originate in circuits outside the brain. Purposeful locomotion requires descending commands from the brain, but we do not understand how these commands are structured. Here, we invest...
Intracellular Ebola virus nucleocapsid assembly revealed by in situ cryo-electron tomography [0.03%]
低温 cryo-电子断层扫描揭示细胞内埃博拉病毒核糖核蛋白装配体结构
Reika Watanabe,Dawid Zyla,Diptiben Parekh et al.
Reika Watanabe et al.
Filoviruses, including the Ebola and Marburg viruses, cause hemorrhagic fevers with up to 90% lethality. The viral nucleocapsid is assembled by polymerization of the nucleoprotein (NP) along the viral genome, together with the viral protein...
Mingliang Jin,Robert I Seed,Guoqing Cai et al.
Mingliang Jin et al.
TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain and presented on immune cell surfaces by covalent association with GARP. Binding to integrin αvβ8 act...
Long-term mesoscale imaging of 3D intercellular dynamics across a mammalian organ [0.03%]
哺乳动物器官的长期三维细胞间动态的中规模成像
Yuanlong Zhang,Mingrui Wang,Qiyu Zhu et al.
Yuanlong Zhang et al.
A comprehensive understanding of physio-pathological processes necessitates non-invasive intravital three-dimensional (3D) imaging over varying spatial and temporal scales. However, huge data throughput, optical heterogeneity, surface irreg...
Neoself-antigens are the primary target for autoreactive T cells in human lupus [0.03%]
新自身抗原是人类狼疮自身反应性T细胞的主要靶点
Shunsuke Mori,Masako Kohyama,Yoshiaki Yasumizu et al.
Shunsuke Mori et al.
Major histocompatibility complex class II (MHC-II) is the most significant genetic risk factor for systemic lupus erythematosus (SLE), but the nature of the self-antigens that trigger autoimmunity remains unclear. Unusual self-antigens, ter...
Intercellular nanotube-mediated mitochondrial transfer enhances T cell metabolic fitness and antitumor efficacy [0.03%]
细胞间纳米管介导的线粒体转移增强T细胞代谢活性和抗肿瘤功效
Jeremy G Baldwin,Christoph Heuser-Loy,Tanmoy Saha et al.
Jeremy G Baldwin et al.
Mitochondrial loss and dysfunction drive T cell exhaustion, representing major barriers to successful T cell-based immunotherapies. Here, we describe an innovative platform to supply exogenous mitochondria to T cells, overcoming these limit...
A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes [0.03%]
发育梯度揭示了单子叶球根植物中真核毒素的生物合成途径
Niraj Mehta,Yifan Meng,Richard Zare et al.
Niraj Mehta et al.
Numerous eukaryotic toxins that accumulate in geophytic plants are valuable in the clinic, yet their biosynthetic pathways have remained elusive. A notable example is the >150 Amaryllidaceae alkaloids (AmAs), including galantamine, an FDA-a...
Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function [0.03%]
利用模版聚合来降解致病性tau聚集体并改善运动功能
Lauren V C Miller,Guido Papa,Marina Vaysburd et al.
Lauren V C Miller et al.
Protein aggregation causes a wide range of neurodegenerative diseases. Targeting and removing aggregates, but not the functional protein, is a considerable therapeutic challenge. Here, we describe a therapeutic strategy called "RING-Bait," ...