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作者:Chen, Yu-Jung; Iyer, Swathi V.; Hsieh, David Chun-Cheng; Li, Buren; Elias, Harold K.; Wang, Tao; Li, Jing; Ganbold, Mungunsarnai; Lien, Michelle C.; Peng, Yu-Chun; Xie, Xuanhua P.; Jayewickreme, Chenura D.; van den Brink, Marcel R. M.; Brady, Sean F.; Lim, S. Kyun; Parada, Luis F.
作者单位:Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Rockefeller University; Rockefeller University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; National Institutes of Health (NIH) - USA; Cornell University; Weill Cornell Medicine; Memorial Sloan Kettering Cancer Center; City of Hope; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
摘要:Glioblastoma is incurable and in urgent need of improved therapeutics(1). Here we identify a small compound, gliocidin, that kills glioblastoma cells while sparing non-tumour replicative cells. Gliocidin activity targets a de novo purine synthesis vulnerability in glioblastoma through indirect inhibition of inosine monophosphate dehydrogenase 2 (IMPDH2). IMPDH2 blockade reduces intracellular guanine nucleotide levels, causing nucleotide imbalance, replication stress and tumour cell death(2). G...
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作者:Iaccarino, Hunter F.; Singer, Annabelle C.; Martorell, Anthony J.; Rudenko, Andrii; Gao, Fan; Gillingham, Tyler Z.; Mathys, Hansruedi; Seo, Jinsoo; Kritskiy, Oleg; Abdurrob, Fatema; Adaikkan, Chinnakkaruppan; Canter, Rebecca G.; Rueda, Richard; Brown, Emery N.; Boyden, Edward S.; Tsai, Li-Huei
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作者:Feldman, Andrew F.; Konings, Alexandra G.; Gentine, Pierre; Cattry, Mitra; Wang, Lixin; Smith, William K.; Biederman, Joel A.; Chatterjee, Abhishek; Joiner, Joanna; Poulter, Benjamin
作者单位:National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland College Park; Stanford University; Columbia University; Indiana University System; Indiana University Indianapolis; University of Arizona; United States Department of Agriculture (USDA); National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
摘要:Rainfall events are globally becoming less frequent but more intense under a changing climate, thereby shifting climatic conditions for terrestrial vegetation independent of annual rainfall totals(1-3). However, it remains uncertain how changes in daily rainfall variability are affecting global vegetation photosynthesis and growth(3-17). Here we use several satellite-based vegetation indices and field observations indicative of photosynthesis and growth, and find that global annual-scale veget...
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作者:Weissmann, Florian; Greiwe, Julia F.; Puhringer, Thomas; Eastwood, Evelyn L.; Couves, Emma C.; Miller, Thomas C. R.; Diffley, John F. X.; Costa, Alessandro
作者单位:Francis Crick Institute; Francis Crick Institute; University of Copenhagen
摘要:Eukaryotic DNA replication begins with the loading of the MCM replicative DNA helicase as a head-to-head double hexamer at origins of DNA replication(1-3). Our current understanding of how the double hexamer is assembled by the origin recognition complex (ORC), CDC6 and CDT1 comes mostly from budding yeast. Here we characterize human double hexamer (hDH) loading using biochemical reconstitution and cryo-electron microscopy with purified proteins. We show that the human double hexamer engages D...
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作者:Hedley, Esme; Ong, Sandy
摘要:These scientists are bringing fresh perspectives to solving the world's big challenges in materials.
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作者:Moorosi, Nyalleng
摘要:Language models developed by big technology companies consistently underperform in African languages. It's time to focus on local solutions.
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作者:Panichello, Matthew F.; Jonikaitis, Donatas; Oh, Yu Jin; Zhu, Shude; Trepka, Ethan B.; Moore, Tirin
作者单位:Stanford University; Stanford University; Howard Hughes Medical Institute
摘要:Persistent, memorandum-specific neuronal spiking activity has long been hypothesized to underlie working memory(1,2). However, emerging evidence suggests a potential role for 'activity-silent' synaptic mechanisms(3-5). This issue remains controversial because evidence for either view has largely relied either on datasets that fail to capture single-trial population dynamics or on indirect measures of neuronal spiking. We addressed this controversy by examining the dynamics of mnemonic informat...
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作者:Dhakal, Sandeep; Parry, Hazel
作者单位:Commonwealth Scientific & Industrial Research Organisation (CSIRO)
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作者:Mayassi, Toufic; Li, Chenhao; Segerstolpe, Asa; Brown, Eric M.; Weisberg, Rebecca; Nakata, Toru; Yano, Hiroshi; Herbst, Paula; Artis, David; Graham, Daniel B.; Xavier, Ramnik J.
作者单位:Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine
摘要:The intestine is characterized by an environment in which host requirements for nutrient and water absorption are consequently paired with the requirements to establish tolerance to the outside environment. To better understand how the intestine functions in health and disease, large efforts have been made to characterize the identity and composition of cells from different intestinal regions(1-8). However, the robustness, nature of adaptability and extent of resilience of the transcriptional ...
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作者:Chaurasia, Anurag
作者单位:Indian Council of Agricultural Research (ICAR); ICAR - Indian Institute of Vegetable Research