45期

最新文章

• Structural immunotherapy: Harnessing chemical design to build powerful next-generation therapeutics AI翻译
  作者：Teplensky, Michelle H.; Bourgeois, Julianna N.; Kudruk, Sergej; Petrosko, Sarah Hurst; Mirkin, Chad A.
  作者单位：Boston University; Northwestern University; Northwestern University; Northwestern University; Chan Zuckerberg Initiative (CZI)
  摘要：Structural immunotherapy relies on the structural features of immunotherapeutics in addition to component identity to influence biodistribution, intra-or extracellular localization, target engagement, and processing kinetics. This strategy is poised to redefine how immunotherapeutics mobilize immunity against disease and transform our ability to harness structure-function relationships to enhance clinical outcomes.
• Modeling protein-small molecule conformational ensembles with PLACER AI翻译
  作者：Anishchenko, Ivan; Kipnis, Yakov; Kalvet, Indrek; Zhou, Guangfeng; Krishna, Rohith; Pellock, Samuel J.; Lauko, Anna; Lee, Gyu Rie; An, Linna; Dauparas, Justas; Dimaio, Frank; Baker, David
  作者单位：University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
  摘要：Modeling the conformational heterogeneity of protein-small molecule interactions is important for understanding natural systems and evaluating designed systems but remains an outstanding challenge. We reasoned that while residue-level descriptions of biomolecules are efficient for de novo structure prediction, for probing heterogeneity of interactions with small molecules in the folded state, an entirely atomic-level description could have advantages in speed and generality. We developed a gra...
• Amino acid insufficiency impairs hepatic vitamin A mobilization in mice AI翻译
  作者：Bhavsar, Chintan T.; Kim, Youn-Kyung; Rodriguez-Polanco, Flavio C.; Zalma, Brian A.; Lopez, Esther M.; Farooq, Saad A.; Ibrahim, Maria; White, Eileen; Anthony, Tracy G.; Quadro, Loredana
  作者单位：Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick
  摘要：Retinol-binding protein 4 (RBP4) is the sole specific serum carrier of vitamin A, delivering it from the hepatic stores to the peripheral organs in a complex with retinol (ROH) and transthyretin (TTR). Regulators of hepatic mobilization aside from vitamin A status itself are ill-defined. Here, we show that amino acid (AA) insufficiency by diet (low-protein, leucine-devoid diet) or drug (asparaginase, ASNase) elevated liver RBP4 without depleting hepatic retinoid stores. In addition, ASNase red...
• Gene drives, species complexes, and the risks of collateral damage AI翻译
  作者：Boete, Christophe
  作者单位：Universite PSL; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; Ecole Pratique des Hautes Etudes (EPHE)
• BRAF inhibition increases TGFβ2 production and stimulates metastasis in mice with endogenous BRAFV600E-induced hepatocellular carcinoma AI翻译
  作者：Cisowski, Jaroslaw; Zowalaty, Ahmed Ezat El; Sayin, Sama I.; Czarnota, Piotr; Gromowski, Tomasz; Eklund, Ella A.; Kashif, Muhammad; Patel, Angana A. H.; Molinaro, Antonio; Lindahl, Per; Wiel, Clotilde; Sayin, Volkan I.; Bergo, Martin O.; Barbacid, Mariano
  作者单位：University of Gothenburg; Jagiellonian University; University of Gothenburg; University of Gothenburg; University of Gothenburg; Sahlgrenska University Hospital; Jagiellonian University; Karolinska Institutet; University of Gothenburg; Sahlgrenska University Hospital
  摘要：The MEK-ERK pathway is a key driver of hepatocellular carcinoma (HCC) pathogenesis, and BRAF mutations, particularly BRAFV600E, can contribute to its activation. Although BRAFV600E mutations are rare in human HCC, they do occur, yet their physiologic impact in liver cells, especially when combined with frequent comutations in tumor suppressor genes, remains poorly understood. Moreover, the effect of BRAF inhibitors on HCC progression and metastasis is not well-defined. Therefore, we developed ...
• The lower boundary of workplace mistreatment: Do small slights matter? AI翻译
  作者：Hodor, Michal; Eldor, Liat; Cappelli, Peter
  作者单位：Tel Aviv University; Tel Aviv University; University of Pennsylvania
  摘要：Recent research in psychology, management, and more recently in economics, highlights the role of individual managers and their behavior in shaping employee performance. While emerging literature on harmful managerial behavior has focused primarily on severe forms of workplace mistreatment, especially various types of harassment, much less is known about its boundary conditions: How minor can a manager's bad behavior be and still negatively affect employee performance? We study what appears to...
• A new late Neanderthal from Crimea reveals long-distance connections across Eurasia AI翻译
  作者：Pigott, Emily M.; Cheshmedzhieva, Konstantina; Zeller, Elke; Sluis, Laura G. Van Der; Chowdhury, Manasij Pal; Gianni, Maddalena; Vegh, Emese; Uthmeier, Thorsten; Chabai, Victor; Patou-Mathis, Marylene; Simkova, Petra G.; Voglmayr, Jana N.; Weber, Gerhard W.; Pinhasi, Ron; Timmermann, Axel; Kuhlwilm, Martin; Douka, Katerina; Higham, Thomas
  作者单位：University of Vienna; University of Arizona; University of Erlangen Nuremberg; National Academy of Sciences Ukraine; Institute of Archaeology, National Academy of Sciences of Ukraine; Museum National d'Histoire Naturelle (MNHN); Institute for Basic Science - Korea (IBS); Pusan National University
  摘要：The Crimean Peninsula contains several important Middle and Upper Paleolithic sites, including Starosele, Kabazi II, and Siuren I. The region has been considered a potential refugium for Neanderthals before their replacement by Homo sapiens. However, no genetic data have been obtained from any of these late Neanderthals, some being inaccessible or badly preserved. Starosele is a notable site which has undergone excavations in recent years. We used collagen peptide mass fingerprinting (Zooarcha...
• Drug- loaded bispecific T cell nanoengager overcomes T cell exhaustion for potent cancer immunotherapy AI翻译
  作者：Wang, Jinjin; Huang, Xisha; Shi, Qiangqiang; Swingle, Kelsey L.; Hamilton, Alex G.; Gong, Ningqiang; Mitchell, Michael J.
  作者单位：University of Pennsylvania; Chinese Academy of Sciences; University of Science & Technology of China, CAS; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; Pennsylvania Medicine
  摘要：Bispecific T cell engager (BiTE) therapeutics that link T cells and tumor cells to induce tumor cell lysis have demonstrated great success in the clinic for the treatment of many cancers. However, T cell exhaustion in the tumor microenvironment leads to tumor cell escape and BiTE therapy resistance. Herein, we developed a drug-loaded bispecific T cell nanoengager (NanoBiTE) to overcome this obstacle. NanoBiTE is composed of a mesoporous silica nanoparticle encapsulating the adenosine A2A recep...
• The geometry of jamming algorithms in the random Lorentz gas AI翻译
  作者：Folena, Giampaolo; Charbonneau, Patrick; Morse, Peter K.; Rojas, Rafael Diaz Hernandez; Ricci-Tersenghi, Federico
  作者单位：Sapienza University Rome; Duke University; Duke University; Seton Hall University; University of Gottingen; Consiglio Nazionale delle Ricerche (CNR); Sapienza University Rome; Istituto Nazionale di Fisica Nucleare (INFN); Istituto di Nanotecnologia (NANOTEC-CNR)
  摘要：Deterministic optimization algorithms unequivocally partition a complex energy landscape into inherent structures (ISs) and their respective basins of attraction. Can these basins be defined solely through geometric principles? This question is paramount to understanding hard sphere jamming, a key model of disordered matter. We here address the issue by proposing a geometric class of gradient descent-like algorithms, which we use to study a system in the hard-sphere universality class, the ran...
• Stimuli- responsive STING nanovaccine for systemic therapy of HPV- induced cancers AI翻译
  作者：Chen, Shuang; Ye, Shuyue; Huang, Gang; Sun, Zhichen; Feng, Qiang; Wang, Maggie; Pantoja, Raymundo; Sumer, Baran D.; Gao, Jinming
  作者单位：University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
  摘要：In recent years, therapeutic cancer vaccines have been extensively investigated, aiming to boost cancer-specific T cells crucial for antitumor activity. The effectiveness of these vaccines is often limited by insufficient immune activation and suboptimal antigen delivery. Stimulator of interferon genes (STING) is an important immune signaling protein that activates host defense genes against infection and cancer. Clinical evaluation of small-molecule STING agonists has shown tepid antitumor re...