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

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• Childhood maltreatment influences adult brain structure through its effects on immune, metabolic, and psychosocial factors (vol 121, e2304704121, 2024) AI翻译
  作者：Orellana, Sofia C.; Bethlehem, Richard A. I.; Simpson-Kent, Ivan L.; van Harmelen, Anne- Laura; Vertes, Petra E.; Bullmore, Edward T.
• Reply to Lockhart et al.: Advancing the understanding of sex differences in functional brain organization with innovative AI tools AI翻译
  作者：Ryali, Srikanth; Zhang, Yuan; Supekar, Kaustubh; Menon, Vinod
  作者单位：Stanford University; Stanford University; Stanford University; Stanford University
• PhiSiCal-Checkup: A Bayesian framework to validate amino acid conformations within experimental protein structures AI翻译
  作者：Amarasinghe, Piyumi R.; Allison, Lloyd; Morton, Craig J.; Stuckey, Peter J.; de la Banda, Maria Garcia; Lesk, Arthur M.; Konagurthu, Arun S.
  作者单位：Monash University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
  摘要：As structural biology and drug discovery depend on high-quality protein structures, assessment tools are essential. We describe a new method for validating amino-acid conformations: PhiSiCal ( tpyix al) Checkup. Twenty new joint probability distributions in the form of statistical mixture models explain the empirical distributions of dihedral angles (0), tp , yi , x 1 , x 2 , ...) of canonical amino acids in experimental protein structures. Marginal and conditional probability distributions fo...
• The effect of CO2 ramping rate on the transient weakening of the Atlantic Meridional Overturning Circulation AI翻译
  作者：Hankel, Camille
  作者单位：University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
  摘要：The Atlantic Meridional Overturning Circulation (AMOC) is a key component of the global climate that is projected to weaken under future anthropogenic climate change. While many studies have investigated the AMOC's response to different levels and types of forcing in climate models, relatively little attention has been paid to the AMOC's sensitivity to the rate of forcing change, despite it also being highly uncertain in future emissions scenarios. In this study, I isolate the AMOC's response ...
• Tsg101 mimicry of canonical E2 enzymes underlies its role in ubiquitin signaling AI翻译
  作者：Nyenhuis, David A.; Watanabe, Susan M.; Tjandra, Nico; Carter, Carol A.
  作者单位：National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); State University of New York (SUNY) System; Stony Brook University; Stony Brook University Hospital
  摘要：Tsg101 is a highly conserved protein best known as an early- functioning component of cellular ESCRT machinery participating in recognition, sorting, and trafficking of cellular cargo to various intracellular destinations. It shares sequence and structural homology to canonical ubiquitin- conjugating (E2) enzymes and is linked to diverse events regulated by Ub signaling. How it might fulfill these roles is unclear. Here, we show that Tsg101 E2 mimicry permits interactions with diverse ubiquiti...
• Triple checkpoint blockade of PD-1, Tim-3, and Lag-3 enhances adoptive T cell immunotherapy in a mouse model of ovarian cancer AI翻译
  作者：Alencar, Gabriel F.; Mohamed, Asmaa O.; Burnett, Madison G.; St Jean, Samantha; Nelson, Anders R.; Su, Yapeng; Voillet, Valentin; Bates, Breanna M.; Suarez, Magdalia Rodgers; Ruskin, Susan L.; Trieu, Lam; Lam, Jennifer L.; Bekiranov, Stefan; Gottardo, Raphael; Greenberg, Philip D.; Anderson, Kristin G.
  作者单位：University of Virginia; University of Virginia; Fred Hutchinson Cancer Center; University of Virginia; University of Virginia; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; University of Virginia; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; Swiss Institute of Bioinformatics; University of Virginia
  摘要：The five-year survival rate for ovarian cancer patients remains below 50%, underscoring the need for innovative therapies. One promising approach involves engineering T cells to specifically target proteins uniquely overexpressed in tumors, thereby controlling tumor growth without toxicity to healthy tissues. Mesothelin (MSLN) contributes to the malignant and invasive phenotype in ovarian cancer and has limited expression in healthy cells, making it a candidate immunotherapy target. Our previo...
• A diverse family of bacterial deubiquitinases is defined by the Coxiella burnetii effector EmcB AI翻译
  作者：Duncan-Lowey, Jeffrey K.; Roy, Craig R.
  作者单位：Yale University
  摘要：The obligate intracellular pathogen Coxiella burnetii encodes a deubiquitinase called EmcB that prevents signaling by the host immune sensor Retinoic acid Inducible Gene I (RIG-I). The evolutionary relationship between EmcB and other deubiquitinases is currently unknown. Here, we show that EmcB defines a broad family of bacterial deubiquitinases divergently evolved from the eukaryotic Ovarian Tumor (OTU) family of deubiquitinases. Our data indicate that the emcB gene has an internal gene rearr...
• The potential impacts of human genetics on virus emergence AI翻译
  作者：Langlois, Ryan A.; Casanova, Jean- Laurent
  作者单位：University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Rockefeller University; Howard Hughes Medical Institute; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP
  摘要：Human monogenic traits can confer resistance to viral disease in infected individuals. Enhanced susceptibility can be driven directly by mutations in genes essential for control of the virus or indirectly via the production of autoantibodies against components of host defense. While the impact of viruses on individuals carrying these genotypes permitted their identification and has been amply studied, little is known about the impact of these human genotypes on the natural history of viruses, ...
• Spin-resolved imaging of atomic-scale helimagnetism in mono-and bilayer NiI2 AI翻译
  作者：Miao, Mao-Peng; Liu, Nanshu; Zhang, Wen-Hao; Zhou, Jian-Wang; Wang, Dao-Bo; Wang, Cong; Ji, Wei; Fu, Ying-Shuang
  作者单位：Huazhong University of Science & Technology; Huazhong University of Science & Technology; Renmin University of China; Renmin University of China; Southwest University - China
  摘要：Noncollinear magnetic orders in monolayer van der Waals magnets are crucial for probing delicate magnetic interactions under minimal spatial constraints and advancing miniaturized spintronic devices. Despite their significance, achieving atomic-scale identification remains challenging. In this study, we utilized spin-polarized scanning tunneling microscopy and density functional theory calculations to identify spin-spiral orders in mono-and bilayer NiI2, grown on graphene-covered SiC(0001) sub...
• Employing deep mutational scanning in the Escherichia coli periplasm to decode the thermodynamic landscape for amyloid formation AI翻译
  作者：McKay, Conor E.; Deans, Miles; Connor, Jack; Saunders, Janet C.; Lloyd, Christopher; Radford, Sheena E.; Brockwell, David J.
  作者单位：University of Leeds; University of Leeds; AstraZeneca
  摘要：Deep mutational scanning (DMS) assays provide a powerful method to generate large-scale datasets essential for advancing AI-driven predictions in biology. The tripartite beta- lactamase assay (TPBLA), in which a protein of interest is inserted between two domains of beta- lactamase, has previously been reported as capable of detecting and quantitating the aggregation of proteins and biologics in the oxidizing periplasm of Escherichia coli and used as a platform for identifying small molecule i...