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• De novo-designed pMHC binders facilitate T cell-mediated cytotoxicity toward cancer cells AI翻译
  作者：Johansen, Kristoffer Haurum; Wolff, Darian Stephan; Scapolo, Beatrice; Fernandez-Quintero, Monica L.; Christensen, Charlotte Risager; Loeffler, Johannes R.; Rivera-de-Torre, Esperanza; Overath, Max D.; Munk, Kamilla Kjaergaard; Morell, Oliver; Viuff, Marie Christine; Lacunza, Inigo; Englund, Alberte T. Damm; Due, Mathilde; Gharpure, Anant; Forli, Stefano; Pardo, Carlos Rodriguez; Tamhane, Tripti; Andersen, Emma Qingjie; Bjoernsson, Kasper Haldrup; Fernandes, Jordan Sylvester; Voss, Lasse Frank; Thumtecho, Suthimon; Ward, Andrew B.; Ormhoj, Maria; Hadrup, Sine Reker; Jenkins, Timothy P.
  作者单位：Technical University of Denmark; Technical University of Denmark; Scripps Research Institute
  摘要：The recognition of intracellular antigens by CD8+ T cells through T cell receptors (TCRs) is central for adaptive immunity against infections and cancer. However, the identification of TCRs from patient material remains complex. We present a rapid de novo minibinder (miBd) design platform leveraging state-of-the-art generative models to engineer miBds targeting the cancer-associated peptide-bound major histocompatibility complex (pMHC) SLLMWITQC/HLA-A*02:01 (NY-ESO-1). Incorporating in silico ...
• Global patterns and drivers of untracked industrial fishing in coastal marine protected areas AI翻译
  作者：Seguin, Raphael; Le Manach, Frederic; Devillers, Rodolphe; Velez, Laure; Mouillot, David
  作者单位：Ifremer; Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); Universite de Montpellier; University of La Reunion; Universite de Montpellier
  摘要：Marine protected areas (MPAs) are expanding worldwide, but industrial fishing within their boundaries remains poorly understood. By combining vessel Global Positioning System data with satellite imagery, we detected industrial fishing in 47% of coastal MPAs worldwide between 2022 and 2024, with two-thirds of vessel detections (67%) untracked by public monitoring. These untracked vessels were most prevalent (80%) in MPAs with the most restrictive management category, which aims to prohibit all ...
• Flat optics produces quantum graphs AI翻译
  作者：Shcherbakov, Maxim R.
  作者单位：University of California System; University of California Irvine
• 'Wandering scholars' analysis reveals how location drives productivity AI翻译
  作者：Langin, Katie
• Genetics, energetics, and allostery in proteins with randomized cores and surfaces AI翻译
  作者：Escobedo, Albert; Voigt, Gesa; Faure, Andre J.; Lehner, Ben
  作者单位：Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Wellcome Trust Sanger Institute; Pompeu Fabra University; ICREA
  摘要：A lack of systematic experimental data limits our understanding of protein evolution. In this study, we experimentally characterized proteins with randomized sequences. Vast numbers of amino acid combinations constitute stable protein cores and surfaces. However, alternative cores frequently disrupt protein function by indirect allosteric effects. Both protein stability and binding can be predicted using simple additive energy models with a small contribution from pairwise energetic couplings....
• Weaponizing Europe's borders imperils wildlife AI翻译
  作者：Nowak, Katarzyna; Cerri, Jacopo; Kudrenko, Svitlana; Kopatz, Alexander; Stachowicz, Izabela; Selva, Nuria; Berhe, Asmeret Asefaw; Kojola, Ilpo; Sprem, Nikica
  作者单位：Polish Academy of Sciences; Mammal Research Institute of the Polish Academy of Sciences; Norwegian University of Life Sciences; Norwegian Institute Nature Research; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD); Polish Academy of Sciences; Universidad de Huelva; University of California System; University of California Merced; Natural Resources Institute Finland (Luke); University of Zagreb
• BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction AI翻译
  作者：Simanshu, Dhirendra K.; Xu, Rui; Stice, James P.; Czyzyk, Daniel J.; Feng, Siyu; Denson, John-Paul; Riegler, Erin; Yang, Yue; Zhang, Cathy; Donovan, Sofia; Smith, Brian P.; Abreu-Blanco, Maria; Chen, Ming; Feng, Cindy; Fu, Lijuan; Rabara, Dana; Young, Lucy C.; Dyba, Marcin; Yan, Wupeng; Lin, Ken; Ghorbanpoorvalukolaie, Samar; Larsen, Erik K.; Malik, Wafa; Champagne, Allison; Parker, Katie; Ju, Jin Hyun; Jeknic, Stevan; Esposito, Dominic; Turner, David M.; Lightstone, Felice C.; Wang, Bin; Wehn, Paul M.; Wang, Keshi; Stephen, Andrew G.; Maciag, Anna E.; Hata, Aaron N.; Sinkevicius, Kerstin W.; Nissley, Dwight V.; Wallace, Eli M.; McCormick, Frank; Beltran, Pedro J.
  作者单位：National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
  摘要：BBO-10203 is an orally available drug that covalently and specifically binds to the rat sarcoma (RAS)-binding domain of phosphoinositide 3-kinase alpha (PI3K alpha), preventing its activation by HRAS, NRAS, and KRAS. It inhibited PI3K alpha activation in tumors with oncogenic mutations in KRAS or PIK3CA and in tumors with human epidermal growth factor receptor 2 (HER2) amplification or overexpression. In preclinical models, BBO-10203 caused significant tumor growth inhibition across multiple t...
• 撤稿声明: A bacterium that can grow by using arsenic instead of phosphorus AI翻译
  作者：Thorp, H. Holden
• Atom-by-atom imaging of moiré phasons with electron ptychography AI翻译
  作者：Zhang, Yichao; Ahammed, Ballal; Bae, Sang Hyun; Lee, Chia-Hao; Huang, Jeffrey; Hossain, Mohammad Abir; Rakib, Tawfiqur; van der Zande, Arend M.; Ertekin, Elif; Huang, Pinshane Y.
  作者单位：University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University System of Maryland; University of Maryland College Park; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
  摘要：Twisted two-dimensional materials exhibit distinctive vibrational modes called moir & eacute; phonons, which arise from the moir & eacute; superlattice. Here, we demonstrate atom-by-atom imaging of phasons, an ultrasoft class of moir & eacute; phonons in twisted bilayer tungsten diselenide (WSe2). Using ultrahigh-resolution (<15 picometers) electron ptychography, we imaged the size and shape of each atom to extract time-averaged vibrational amplitudes as a function of twist angle and position....
• Molecular glues that facilitate RAS binding to PI3Kα promote glucose uptake without insulin AI翻译
  作者：Terayama, Koji; Furuzono, Shinji; Fer, Nicole; Yan, Wupeng; Young, Lucy C.; Czyzyk, Daniel J.; Goldstein de Salazar, Ruby; Sasaki, Masato; Uozumi, Akihiro; Konishi, Masahiro; Kanda, Shoichi; Sogawa, Yoshitaka; Yamaguchi, Mitsuhiro; Tsuji, Takashi; Kuroyanagi, Junichi; Hayashi, Mayumi; Ogura, Yuji; Simanshu, Dhirendra K.; Kubota, Kazuishi; Tanaka, Jun; McCormick, Frank
  作者单位：Daiichi Sankyo Company Limited; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Daiichi Sankyo Company Limited; Daiichi Sankyo Company Limited; Daiichi Sankyo Company Limited
  摘要：While exploring strategies to control blood glucose concentrations in diabetes, we identified so-called molecular glues D223 and D927 that promote glucose uptake in the absence of insulin. They act by increasing the binding affinity of phosphoinositide 3-kinase alpha (PI3K alpha) catalytic subunit p110 alpha to canonical small guanosine triphosphatase RAS proteins and to RRAS, RRAS2, and MRAS by three orders of magnitude. The compounds bind to the RAS-binding domain of p110 alpha, stabilizing ...