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

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• Reply to Ritson-Williams et al. and Loya and van Woesik: Coral replacement research is vital due to uncertainty and unprecedented stress AI翻译
  作者：Camacho, Alejandro E.; Dana, David A.; Matz, Mikhail
  作者单位：University of California System; University of California Los Angeles; Northwestern University; University of Texas System; University of Texas Austin
• Multiplex gene editing enables the multibiofortification of essential vitamins and other health-promoting phytonutrients in tomato AI翻译
  作者：Hong, Yechun; Yu, Zongjun; Zhu, Wenbo; Sun, Jialei; Zhu, Zeyao; Wang, Zhen; Cao, Minjie; Lang, Zhaobo; Lyu, Yu-Xuan; Liu, Pengpeng; Zhu, Jian-Kang
  作者单位：Southern University of Science & Technology; Southern University of Science & Technology; Anhui Agricultural University; Macau University of Science and Technology
  摘要：Dietary deficiencies in essential micronutrients and other phytonutrients represent a global health and economic burden, contributing to hidden hunger and chronic diseases. While genome editing has been employed to improve individual nutritional traits in crops, multibiofortification through simultaneous modification of multiple distinct metabolic pathways is more challenging. Here, we designed a multiplex CRISPR-Cas strategy to edit five key genes in tomato: Sl7-DR2, SlGAD3, SlSGR1, SlGGP1, a...
• Illuminating proinflammatory myeloid cells with PET tracers targeting GPR84 AI翻译
  作者：Kalita, Mausam; Kuo, Renesmee C.; Straniero, Valentina; Reyes, Samantha T.; Pandrala, Mallesh; Lanzini, Alessia; Marsango, Sara; D'Moore, Desiree; Mahn, Piper; Setiadi, Andrew; Sundar, Mira; Mak, Spencer; Nagy, Sydney; Alam, Israt S.; Jain, Poorva; Inay, Grace; Malek, Rim; Brooks, Allen F.; Beinat, Corinne; Valoti, Ermanno; Scott, Peter J. H.; Milligan, Graeme; James, Michelle L.
  作者单位：Stanford University; Stanford Medicine; Stanford University; University of Milan; University of Glasgow; University of Michigan System; University of Michigan; Stanford University; Stanford Medicine
  摘要：Innate immunity mediated by myeloid cells defends against infection and injury, but when chronically activated, it drives tissue damage and neurodegeneration. Molecular imaging with positron emission tomography (PET) enables noninvasive, real-time monitoring of such processes in vivo. However, most current neuroinflammation PET tracers lack specificity for activated myeloid cells. G protein-coupled receptor 84 (GPR84) is a promising biomarker that is selectively upregulated on activated microg...
• ICMT supports BRAFV600E-driven tumor growth by membrane targeting of the CAAX protein INPP5E AI翻译
  作者：Yang, Xijie; Qiao, Xi; Schmidt, Sarah; Eklund, Ella A.; Ebner-Walter, Carolina; Ivarsson, Emil; Crespo, Michelle Ann; Kersemakers, Nadieh; Dzanan, Jozefina J.; Thorisson, Bjarni; Lundgren, Christine; Lim, Hooi Ching; Shkoukani, Sam; Tuksammel, Elin; Xu, Xiufeng; Sayin, Volkan I.; Martin-Fontecha, Mar; Ortega-Gutierrez, Silvia; Dalin, Martin; Bergo, Martin O.
  作者单位：Karolinska Institutet; University of Gothenburg; University of Gothenburg; University of Gothenburg; Complutense University of Madrid; Complutense University of Madrid; University of Gothenburg
  摘要：Isoprenylcysteine carboxyl methyltransferase (ICMT) catalyzes C-terminal methylation of prenylated CAAX proteins, a final processing step promoting membrane association and signaling. Although ICMT has been pursued to disrupt RAS membrane targeting, its role in BRAFV600E-driven cancers and critical substrates remains unclear. Here, genetic and pharmacologic (UCM-1336) ICMT inhibition suppressed proliferation and invasion in BRAFV600E-mutant melanoma cells and reduced tumor growth in xenografts...
• Coordinated stomatal, mesophyll, and biochemical functions in photosynthetic responses to heat and dryness AI翻译
  作者：Hu, Xingyu; Wong, Suan Chin; Farquhar, Graham D.
  作者单位：Tsinghua University; Australian National University
  摘要：The intrinsic link between temperature and leaf-to-air vapor pressure difference (Delta e) complicates isolation of their individual effects on photosynthesis. Consequently, how CO2 diffusion changes under heat and high evaporative demand, particularly through mesophyll conductance (g(m)) responses, remains poorly understood. The conditions under which biochemical colimitation occurs, meaning Rubisco carboxylation and RuBP regeneration capacities match, are also unclear. To advance understandi...
• The rising threats of global wildland-human interface revealed by a scale-adaptive approach AI翻译
  作者：Xia, Junnan; Kong, Xuesong; Jiao, Limin; Wei, Wei; Liu, Lingbo; Hu, Yuanchao; Wang, Zhen; Hong, Mengyao; Liu, Yaolin
  作者单位：Wuhan University; Jianghan University; Wuhan University; Harvard University; Guangdong University of Technology; Huazhong Agricultural University
  摘要：The Wildland-Human Interface (WHI), where human infrastructure and activities meet or intermingle with wildland vegetation, represents a critical zone of human-environmental conflict. Here, we present the first global map to explicitly differentiate the WHI into its Wildland-Urban Interface (WUI) and Wildland-Agriculture Interface (WAI) components between 2000 and 2020, using a scale-adaptive HEALpix Quadtree algorithm. We show that the global WHI covered 4.87% of terrestrial area in 2020, wit...
• Self-cleavage-dependent and-independent functions of Adgrg1/Gpr56 in mice AI翻译
  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...
• Mechanism of MutLβ-dependent DNA expansions AI翻译
  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...
• PPP1R3G-RIPK1-ZBP1 axis activates early-stage apoptosis and late-stage necroptosis to promote doxorubicin-induced cardiotoxicity AI翻译
  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...
• Selective depletion of virus-specific CD8 T cells from the liver after PD-1 therapy with Fc-intact antibody during chronic infection AI翻译
  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...