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

最新文章

• Engineering a protease-stable, oral single-domain antibody to inhibit IL-23 signaling AI翻译
  作者：Ota, Naruhisa; Davies, Christopher W.; Kang, Jing; Yan, Donghong; Scherl, Alexis; Wong, Anne; Cook, Ryan; Tao, Xun; Dunlap, Debra; Klabunde, Sha; Mantik, Priscilla; Mohanan, Vishnu; Lin, WeiYu; McBride, Jacqueline; Sadekar, Shraddha; Storek, Kelly M.; Lupardus, Patrick; Ye, Zhengmao; Wallweber, Heidi Ackerly; Kiefer, James R.; Xu, Min; Chan, Pamela; Nagapudi, Karthik; Xi, Tangshen; Koerber, James T.
  作者单位：Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech
  摘要：Interleukin (IL)- 23 is a validated therapeutic target in inflammatory bowel disease. While antibodies targeting IL23 demonstrate clinical efficacy, they face challenges such as high costs, safety risks, and the necessity of parenteral administration. Here, we present a workflow to simultaneously enhance the affinity and protease stability of an anti- IL23R VHH employs both CDR and framework residues to achieve picomolar affinity for IL23R. The engineered VHH remains stable for over 8 h in int...
• Robustness revisited: On the neutral evolution of centrality and localization AI翻译
  作者：Sella, Yehonatan; Bergman, Aviv
  作者单位：Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; The Santa Fe Institute
  摘要：This study investigates the intricate interplay among neutral landscape structure, mutation rate, recombination rate, and population dynamics in shaping evolutionary robustness. We provide a comprehensive framework that elucidates how different evolutionary forces interact to influence genotypic robustness and localization within haploid and diploid populations. We demonstrate that in haploid populations, high mutation rates relative to recombination typically drive the population toward regio...
• Macrophages release neuraminidase and cleaved calreticulin for programmed cell removal AI翻译
  作者：Banuelos, Allison; Baez, Michelle; Zhang, Allison; Yilmaz, Leyla; Kasberg, William; Volk, Regan; Georgeos, Nardin; Sedova, Elle Koren -; Le, Uyen; Burden, Andrew T.; Marjon, Kristopher D.; Schwartz, Jennifer Lippincott -; Zaro, Balyn W.; Weissman, Irving L.
  作者单位：Stanford University; Stanford University; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Stanford University
  摘要：Calreticulin (CALR) is primarily an endoplasmic reticulum chaperone protein that also plays a key role in facilitating programmed cell removal (PrCR) by acting as an eat-me signal for macrophages, directing their recognition and engulfment of dying, diseased, or unwanted cells. Recent findings have demonstrated that macrophages can transfer their own CALR onto exposed asialoglycans on target cells, marking them for PrCR. Despite the critical role CALR plays in this process, the molecular mecha...
• Trait-space patterning is dictated by the tempo and mode of mutation AI翻译
  作者：Martis, Stephen; Schwab, David J.; Grandpre, Trevor
  作者单位：Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Princeton University; City University of New York (CUNY) System; Princeton University; Princeton University
  摘要：In large, natural ecosystems, many (>= 1) phenotypically relevant mutants can emerge over the characteristic turnover time of the population. When this is the case, there can be `eco-evolutionary feedback' between the dynamical processes that underlie mutation, selection and ecology. We show that, owing to such feedback, the precise details of the mutational process can have a qualitative impact on the long-term behavior of an eco-evolutionary system, in contrast to the classical population ge...
• Interpreting dynamic-compression experiments to uncover the time dependence of freezing: Application to gallium AI翻译
  作者：Belof, Jonathan L.; Brown, Justin L.; Myint, Philip C.; Sterbentz, Dane M.; Hao, Yue; Stoltzfus, Brian S.; Benedict, Lorin X.
  作者单位：United States Department of Energy (DOE); Lawrence Livermore National Laboratory; United States Department of Energy (DOE); Sandia National Laboratories
  摘要：Using pulsed-power magnetic field sources to compress gallium to gigapascal pressures on nanosecond timescales, we report here experiments on shockless dynamic compression of a liquid metal. Time-resolved velocimetry data reveal signatures of rapid freezing from a metastable liquid state, and we demonstrate that the kinetics of this nonequilibrium solidification can be accurately simulated with a computational modeling framework we have developed in previous studies, where classical nucleation...
• Quadruple adenine base-edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease-engineered T cells AI翻译
  作者：Engel, Nils W.; Steinfeld, Israel; Ryan, Daniel; Anupindi, Kusala; Kim, Samuel; Wellhausen, Nils; Chen, Linhui; Wilkins, Katherine; Baker, Daniel J.; Rommel, Philipp C.; Jarocha, Danuta; Gohil, Mercy; Zhang, Qian; Milone, Michael C.; Fraietta, Joseph A.; Davis, Megan; Young, Regina M.; June, Carl H.
  作者单位：University of Pennsylvania; Agilent Technologies; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania
  摘要：Genome-editing technologies have enabled the clinical development of allogeneic cellular therapies, yet the optimal gene-editing modality for multiplex editing of therapeutic T cell product manufacturing remains elusive. In this study, we conducted a comprehensive comparison of CRISPR/Cas9 nuclease and adenine base editor (ABE) technologies in generating allogeneic chimeric antigen receptor (CAR) T cells, utilizing extensive in vitro and in vivo analyses. Both methods achieved high editing eff...
• QnAs with Thomas A. Henzinger AI翻译
  作者：Ravindran, Sandeep
• Molecular determinants of sialylated IgG anti-inflammatory activity AI翻译
  作者：Sneed, Sunny L.; Strandberg, Elizabeth A.; Laureano, Ana F. S.; Vattepu, Ravi; Sun, Yehao; Tran, Truc T.; Conroy, Michelle E.; Anthony, Robert M.
  作者单位：Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of North Carolina; East Carolina University; Amgen
  摘要：IgG antibodies are the basis for many successful therapeutics. A single, N-linked glycan is present on the Fc on all IgGs, and the composition of that glycan exerts marked influence over effector functions of the IgG. We and others have shown terminal sialylation of the Fc glycan confers anti-inflammatory activity to the IgG1 subclass and is thought to be responsible for the anti-inflammatory activity of high-dose intravenous immunoglobulin. However, whether sialylation results in anti-inflamm...
• Reply to Royka and Santos: Representing ignorance, and the evolution of theory of mind AI翻译
  作者：Townrow, Luke A.; Krupenye, Christopher
  作者单位：Johns Hopkins University
• AI assistance improves people's ability to distinguish correct from incorrect eyewitness lineup identifications AI翻译
  作者：Kelso, Lauren E.; Dobolyi, David G.; Grabman, Jesse H.; Dodson, Chad S.
  作者单位：University of Virginia; University of Colorado System; University of Colorado Boulder; New Mexico State University
  摘要：Mistaken eyewitness identification is one of the leading causes of false convictions. Improving law enforcement's ability to identify correct identifications could have profound implications for criminal justice. Across two experiments, we show that AI-assistance can improve people's ability to distinguish between accurate and inaccurate eyewitness lineup identifications. Participants (Experiment 1: N = 1,092, Experiment 2: N = 1,809) saw an eyewitness's lineup identification, accompanied by t...