作者：Krasnow, Nicholas A.; Xu, Joy A.; Zhang, Emily; Mahadeshwar, Gandhar K.; Tao, Y. Allen; McCreary, Julia; Hemez, Colin F.; Brown, Logan E.; Jiang, Wei; Liu, David R.
作者单位：Harvard University; Harvard University; Howard Hughes Medical Institute; Harvard Medical School
摘要：Engineered or laboratory-evolved proteins often have suboptimal stability, activity or specificity. Here we applied artificial intelligence (AI)-based protein sequence design to address challenges in experimental enzyme evolution. Using the model ProteinMPNN, we redesigned three distinct botulinum neurotoxin (BoNT) proteases, generating variants with improved stability and full catalytic efficiency1. We hypothesized that redesigned enzymes may be more mutationally robust than their wild-type (...
作者：Desharnais, Lysanne; Swaby, Anikka; Messaoudene, Meriem; Dore, Samuel; Yu, Miranda W.; Fiset, Benoit; Breton, Valerie; Ponce, Mayra; Hu, Yongjia; Wilson, Liam; Sorin, Mark; Wang, Ye; Dewar, Ken; Pollak, Michael; Elkrief, Arielle; Routy, Bertrand; Walsh, Logan A.; Quail, Daniela F.
作者单位：McGill University; McGill University; McGill University; Universite de Montreal; McGill University; McGill University; McGill University; McGill University; Universite de Montreal
摘要：Physiological host factors, such as the gut microbiome and obesity, independently influence anti-tumour immunity and responses to immune checkpoint inhibitors (ICIs)1, with high body mass index (BMI) having an unexpected link with greater ICI efficacy2, 3, 4, 5-6. However, how these factors interact across diverse dietary contexts remains unclear. Here, using 12 mouse diet models that reflect a spectrum of obesity biology, we characterize diet-driven metabolic, immune and gut microbiota featur...
作者：Ahanger, Sajad Hamid; Semenza, Evan R.; Zhang, Chujing; Gil, Eugene; Cole, Mitchel A.; Lu, Serena Huei-An; Wang, Li; Kriegstein, Arnold R.; Lim, Daniel A.
作者单位：University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
摘要：The nuclear genome is spatially organized into a three-dimensional architecture by physical association of large chromosomal domains with subnuclear compartments including the nuclear lamina at the radial periphery and nuclear speckles within the nucleoplasm1, 2, 3, 4-5. However, how higher-order spatial genome architecture regulates human development has been overlooked, and the interplay between chromatin state and subnuclear genome compartmentalization is poorly understood. Here we generate...
