-
作者：Tsuchida, Connor A.; Wasko, Kevin M.; Hamilton, Jennifer R.; Doudna, Jennifer A.
作者单位：University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California San Francisco; The J David Gladstone Institutes; Howard Hughes Medical Institute; University of California System; University of California Berkeley
摘要：Cell- type- specific in vivo delivery of genome editing molecules is the next breakthrough that will drive biological discovery and transform the field of cell and gene therapy. Here, we discuss recent advances in the delivery of CRISPR-Cas genome editors either as preassembled ribonucleoproteins or encoded in mRNA. Both strategies avoid pitfalls of viral vector- mediated delivery and offer advantages including transient editor lifetime and potentially streamlined manufacturing capability that...
-
作者：Zimmerman, Lior; Alon, Noga; Levin, Itay; Koganitsky, Anna; Shpigel, Nufar; Brestel, Chen; Lapidoth, Gideon D.
摘要：The potential of engineered enzymes in industrial applications is often limited by their expression levels, thermal stability, and catalytic diversity. De novo enzyme design faces challenges due to the complexity of enzymatic catalysis. An alternative approach involves expanding natural enzyme capabilities for new substrates and parameters. Here, we introduce CoSaNN (Conformation Sampling using Neural Network), an enzyme design strategy using deep learning for structure prediction and sequence...
-
作者：Katsumura, Koichi R.; Liu, Peng; Kim, Jeong-ah; Mehta, Charu; Bresnick, Emery H.
作者单位：University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
摘要：Mutations in genes encoding transcription factors inactivate or generate ectopic activities to instigate pathogenesis. By disrupting hematopoietic stem/progenitor cells, GATA2 germline variants create a bone marrow failure and leukemia predisposition, GATA2 deficiency syndrome, yet mechanisms underlying the complex phenotypic constellation are unresolved. We used a GATA2- deficient progenitor rescue system to analyze how genetic variation influences GATA2 functions. Pathogenic variants impaire...
-
作者：Li, Jian-Feng; Cheng, Wen-Yan; Lin, Xiang-Jie; Wen, Li-Jun; Wang, Kai; Zhu, Yong-Mei; Zhu, Hong-Ming; Chen, Xin-Jie; Zhang, Yu-Liang; Yin, Wei; Zhang, Jia-Nan; Yi, Xiao; Zhang, Fan; Weng, Xiang-Qin; Wang, Sheng-Yue; Jiang, Lu; Wu, Hui-Yi; Ren, Jia-Qi; Lin, Xiao-Jing; Qiao, Niu; Dai, Yu-Ting; Fang, Hai; Tan, Yun; Sun, Xiao-Jian; Lv, Gang; Yan, Xiao-Yu; Chen, Su-Ning; Chen, Zhu; Jin, Jie; Wu, De-Pei; Ren, Rui-Bao; Chen, Sai-Juan; Shen, Yang
作者单位：Shanghai Jiao Tong University; Chinese Academy of Sciences; Zhejiang University; Soochow University - China; Soochow University - China; Hainan Medical University; Zhejiang University
摘要：Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging- related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyz...
-
作者：Hong, Suk - Hyun; Castro, Glenda; Wang, Dan; Nofsinger, Russell; Kane, Maureen; Folias, Alexandra; Atkins, Annette R.; Yu, Ruth T.; Napoli, Joseph L.; Sassone-Corsi, Paolo; de Rooij, Dirk G.; Liddle, Christopher; Downes, Michael; Evans, Ronald M.
作者单位：Salk Institute; University of California System; University of California Berkeley; University of California System; University of California Irvine; Institut National de la Sante et de la Recherche Medicale (Inserm); Utrecht University; University of Sydney; Westmead Institute for Medical Research; University of Sydney; Bristol-Myers Squibb
摘要：Despite numerous female contraceptive options, nearly half of all pregnancies are unintended. Family planning choices for men are currently limited to unreliable condoms and invasive vasectomies with questionable reversibility. Here, we report the development of an oral contraceptive approach based on transcriptional disruption of cyclical gene expression patterns during spermatogenesis. Spermatogenesis involves a continuous series of self- renewal and differentiation programs of spermatogonia...
-
作者：Shukla, Sankalp; Chen, Wei; Rao, Shanlin; Yang, Serim; Ou, Chenxi; Larsen, Kevin P.; Hummer, Gerhard; Hanson, Phyllis I.; Hurley, James H.
作者单位：University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Michigan System; University of Michigan; Max Planck Society; Goethe University Frankfurt; University of California System; University of California Berkeley
摘要：Apoptosis linked Gene - 2 (ALG-2) is a multifunctional intracellular Ca2+ sensor and the archetypal member of the penta-EF hand protein family. ALG-2 functions in the repair of damage to both the plasma and lysosome membranes and in COPII- dependent budding at endoplasmic reticulum exit sites (ERES). In the presence of Ca2+, ALG-2 binds to ESCRT-I and ALIX in membrane repair and to SEC31A at ERES. ALG-2 also binds directly to acidic membranes in the presence of Ca2+ by a combination of electro...
-
作者：Kiat, Yosef; O'Connor, Jingmai K.
作者单位：Field Museum of Natural History (Chicago)
摘要：As a fundamental ecological aspect of most organisms, locomotor function significantly constrains morphology. At the same time, the evolution of novel locomotor abilities has produced dramatic morphological transformations, initiating some of the most significant diversifications in life history. Despite significant new fossil evidence, it remains unclear whether volant locomotion had a single or multiple origins in pennaraptoran dinosaurs and the volant abilities of individual taxa are contro...
-
作者：Guo, Qian; Chen, Kai-en; Gimenez-Andres, Manuel; Jellett, Adam P.; Gao, Ya; Simonetti, Boris; Liu, Meihan; Danson, Chris M.; Heesom, Kate J.; Cullen, Peter J.; Collins, Brett M.
-
作者：Aassve, Arnstein; Adsera, Alicia; Chang, Paul Y.; Mencarini, Letizia; Park, Hyunjoon; Peng, Chen; Plach, Samuel; Raymo, James M.; Wang, Senhu; Yeung, Wei-Jun Jean
作者单位：Bocconi University; Bocconi University; Princeton University; Princeton University; Harvard University; University of Pennsylvania; Princeton University; University of Tokyo; National University of Singapore; National University of Singapore; Agency for Science Technology & Research (A*STAR)
摘要：Taking stock of individuals' perceived family ideals is particularly important in the current moment given unprecedented fertility declines and the diversification of households in advanced industrial societies. Study participants in urban China, Japan, South Korea, Singapore, the United States, Italy, Spain, and Norway were asked to evaluate vignettes describing families whose characteristics vary on ten dimensions. In contrast to previous studies that focused on a single dimension, such as f...
-
作者：Butruille, Thomas; Crone, Joshua C.; Portela, Carlos M.
作者单位：Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
摘要：Ultralight architected materials enabled by advanced manufacturing processes have achieved density-normalized strength and stiffness properties that are inaccessible to bulk materials. However, the majority of this work has focused on static loading and elastic-wave propagation. Fundamental understanding of the mechanical behavior of architected materials under large-deformation dynamic conditions remains limited, due to the complexity of mechanical responses and shortcomings of characterizati...
