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作者：Kwarcinski, Frank E.; Bernadyn, Tyler F.; Teuber, James P.; Nascimento, Mariane; Bergin, Ingrid; Shen, Tingzhen; Gandhi, Riya; Lu, Xinyi; Brody, Matthew J.; Holinstat, Michael; Tall, Gregory G.
作者单位：University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
摘要：Adhesion G protein-coupled receptors (AGPCRs) regulate essential physiological processes through interactions between their ectodomains and adjacent cell surface proteins or extracellular matrix components (ECM). AGPCRs distinctively arrive at the plasma membrane as self-cleaved holoreceptors with noncovalently associated N-terminal (NTF) and C-terminal fragments (CTF). Canonical AGPCR signaling proceeds in three sequential steps; NTF adhesive domains bind to ligands, extracellular shear force...
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作者：Kadyrova, Lyudmila Y.; Kadyrov, Farid F.; Hayward, Bruce; Usdin, Karen; Kadyrov, Farid A.
作者单位：Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Southern Illinois University System; Southern Illinois University; Washington University (WUSTL); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
摘要：MutS and MutL proteins and their eukaryotic homologs have important functions in DNA metabolism. MutL beta (MLH1-PMS1 heterodimer) is a poorly understood eukaryotic MutL complex. Recent genetic studies have implicated MutL beta in the process of expansion of the short, tandem DNA repeat tracts that is responsible for the repeat expansion diseases. The function of MutL beta and the mechanism of MutL beta-dependent DNA expansions have not been established. We show here that MutL beta promotes Mu...
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作者：Ma, Xueling; Chen, Ken; Wang, Zhigao
作者单位：State University System of Florida; University of South Florida
摘要：Cardiotoxicity is a dose-limiting complication of doxorubicin (DOX) chemotherapy, yet the molecular mechanisms governing the transition from acute stress to terminal heart failure remain incompletely defined. Here, we identify Protein Phosphatase 1 Regulatory Subunit 3G (PPP1R3G) as a central regulator of a RIPK1-ZBP1 signaling axis that drives DOX-induced cardiotoxicity. We demonstrate that DOX initiates a biphasic death program. Initially, DOX triggers p38-mediated inhibitory phosphorylation...
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作者：Hashimoto, Masao; Nasti, Tahseen H.; Jin, Hyun - Tak; Bu, Melissa; Araki, Koichi; Lee, Junghwa; Valanparambil, Rajesh M.; Akhtar, Akil; Khan, Mohammad Affan; Peng, Zhipeng; Hu, Yinghong; McManus, Daniel T.; Bahhar, Ilham; Wieland, Andreas; Davis, Carl W.; Ramalingam, Suresh S.; Sharpe, Arlene H.; Ravetch, Jeffrey V.; Freeman, Gordon J.; Ahmed, Rafi
作者单位：Emory University; Emory University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; University of California System; University of California San Francisco; University System of Ohio; Cincinnati Children's Hospital Medical Center; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Institut Pasteur Korea; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Ropar; University System of Ohio; Ohio State University; Emory University; Emory University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Rockefeller University
摘要：Anti-programmed cell death 1 (PD-1) antibody therapy is now widely used in various cancers. However, the role of the antibody Fc region in PD-1 directed immunotherapy is not well understood. Preclinical studies commonly use species-mismatched rat anti-mouse antibodies, which may not accurately reflect antibody-Fc gamma receptor (Fc gamma R) interactions. Here, we used mouse anti-mouse PD-1 antibodies to investigate how the Fc region influences therapeutic efficacy for enhancing CD8 T cell resp...
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作者：Jordan, Anikka G.; Voss, Joel L.; Kragel, James E.
作者单位：University of Chicago
摘要：The hippocampus supports episodic memory by binding spatial and semantic information, yet how this information is simultaneously organized along its long axis remains debated. Gradient accounts propose a continuous shift in representational scale, from coarse coding in anterior to fine coding in posterior regions, whereas modular accounts posit discrete subregions specialized for distinct functions. Using high-resolution fMRI together with eye tracking as a readout of spatial and semantic memo...
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作者：Li, Ming; Liu, Jianling; Xing, Mingyan; Liu, Han; Wang, Lingxia; Wu, Xiaoxia; Ou, Yangjing; Zhao, Xiaoming; Wang, YangYang; Xie, YangYang; Zhang, Hanwen; Wu, Zhuyang; Hao, Jincheng; Li, Hong; Li, Yu; Zhang, Haibing
作者单位：Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences; Shanghai Institute of Nutrition & Health, CAS
摘要：Receptor-interacting protein kinase 1 (RIPK1) is a key regulator of cell death and inflammation, with its activation modulated by diverse posttranslational modifications. While ubiquitination of RIPK1 at lysine 376 (K376) has been shown to inhibit apoptosis and necroptosis both in vitro and in vivo, its role in inflammation remains undefined. In this study, we introduced a kinase-dead D138N mutation into Ripk1K376R/K376R mice. Notably, Ripk1K376R,D138N/K376R,D138N mice rescued the embryonic le...
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作者：Wang, Wenqing; Cook, David H.; Chen, Xiaoyu; Kumar, Punit; Minor, Andrew M.; Rao, Satish I.; Asta, Mark; Ritchie, Robert O.; Farkas, Diana
作者单位：United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Virginia Polytechnic Institute & State University
摘要：Understanding how grain boundaries mediate fracture remains a critical challenge in designing ductile, high-performance refractory alloys. Here, we extend the Rice-Thomson criterion to account for the angle between cracks and the impinging grain boundaries (GBs), capturing the competition between intergranular fracture and dislocation-mediated plasticity. Using machine learning interatomic potentials, we performed molecular statics simulations to probe fracture mechanisms in nanocrystalline Nb...
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作者：Cote-Gendreau, Marielle
作者单位：Princeton University
摘要：Migration decisions are embedded in social and family trajectories that escape traditional data sources, which tend to observe individuals in isolation. Genealogical microdata now make it possible to trace these dynamics over long time horizons. This paper documents how prior generations' migration histories shape future internal migration behavior, leveraging rich historical microdata spanning over two centuries and multiple generations at the scale of an entire population (Quebec, Canada; 16...
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作者：Liao, Yawen; Yuan, Luezhen; Sornapudi, Trinadha Rao; Land, Max; Gupta, Rajshikhar; Shivashankar, G., V
作者单位：Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
摘要：The integration of environmental cues into cellular programs is crucial for cell function. Yet, how this integration is modulated due to cellular aging remains unclear. We propose that the 3D chromatin organization filters these signals and investigated how age-related chromatin changes in human dermal fibroblasts affect responses to mechanical tension and TGF-beta. Young fibroblasts exhibited synergistic gene expression enhancement in response to combined stimuli, a response that was markedly...
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作者：van Haastert, Peter J. M.
作者单位：University of Groningen
