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作者：Pouikli, Andromachi; Frezza, Christian
作者单位：University of Cologne; University of Cologne
摘要：The metabolism of cancer cells adapts to meet an increased need for the energy, biosynthesis, and antioxidants required for proliferation, tumor growth, and metastasis (1). Yet, whether this metabolic reprogramming affects the recognition and elimination of cancer cells by immune cells has not been well investigated. On page 1316 of this issue, Mangalhara et al. (2) report a connection between a cancer cell's mitochondrial metabolism and its ability to evoke an immune response in a mouse model...
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作者：Jacobs, Phie
摘要：Half-million-year-old structure unearthed in Zambia may have been a platform, bridge, or house foundation
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作者：Rubinoff, Daniel; Gon, Samuel M. 'Ohukani'ohi'a, III
作者单位：University of Hawaii System; Nature Conservancy
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作者：Bjorkland, Rhema
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作者：Brainard, Jeffrey
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作者：Chaplin, Lan Nguyen
作者单位：Northwestern University
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作者：Squair, Jordan W.; Milano, Marco; de Coucy, Alexandra; Gautier, Matthieu; Skinnider, Michael A.; James, Nicholas D.; Cho, Newton; Lasne, Anna; Kathe, Claudia; Hutson, Thomas H.; Ceto, Steven; Baud, Laetitia; Galan, Katia; Aureli, Viviana; Laskaratos, Achilleas; Barraud, Quentin; Deming, Timothy J.; Kohman, Richie E.; Schneider, Bernard L.; He, Zhigang; Bloch, Jocelyne; Sofroniew, Michael V.; Courtine, Gregoire; Anderson, Mark A.
作者单位：Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
摘要：Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show ...
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作者：Marsh, Joseph A.; Teichmann, Sarah A.
作者单位：University of Edinburgh; Wellcome Trust Sanger Institute; University of Cambridge
摘要：Many of the genetic mutations that cause disease in humans occur in protein-coding regions. Although the capacity to sequence DNA and identify these variants has substantially increased, the ability to interpret their effects remains limited. This problem is particularly acute for missense variants, which involve substitution of a single amino acid residue and make up the overwhelming majority of variants of uncertain significance (VUS), as classified by clinicians (1). On page 1303 of this is...
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作者：Horton, Connor A.; Alexandari, Amr M.; Hayes, Michael G. B.; Marklund, Emil; Schaepe, Julia M.; Aditham, Arjun K.; Shah, Nilay; Suzuki, Peter H.; Shrikumar, Avanti; Afek, Ariel; Greenleaf, William J.; Gordan, Raluca; Zeitlinger, Julia; Kundaje, Anshul; Fordyce, Polly M.
作者单位：Stanford University; Stanford University; Stanford University; Stanford University; Stowers Institute for Medical Research; Duke University; Duke University; Weizmann Institute of Science; Duke University; Duke University; University of Kansas; University of Kansas Medical Center; Chan Zuckerberg Initiative (CZI); University of California System; University of California Berkeley; Fred Hutchinson Cancer Center
摘要：Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density, with impacts we...
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作者：Lim, Yang; Tamayo-Orrego, Lukas; Schmid, Ernst; Tarnauskaite, Zygimante; Kochenova, Olga V.; Gruar, Rhian; Muramatsu, Sachiko; Lynch, Luke; Schlie, Aitana Verdu; Carroll, Paula L.; Chistol, Gheorghe; Reijns, Martin A. M.; Kanemaki, Masato T.; Jackson, Andrew P.; Walter, Johannes C.
作者单位：Harvard University; Harvard Medical School; University of Edinburgh; Howard Hughes Medical Institute; Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Stanford University; Stanford University; Graduate University for Advanced Studies - Japan; University of Tokyo; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute
摘要：CDC45-MCM2-7-GINS (CMG) helicase assembly is the central event in eukaryotic replication initiation. In yeast, a multi-subunit pre-loading complex (pre-LC) accompanies GINS to chromatin-bound MCM2-7, leading to CMG formation. Here, we report that DONSON, a metazoan protein mutated in microcephalic primordial dwarfism, is required for CMG assembly in vertebrates. Using AlphaFold to screen for protein-protein interactions followed by experimental validation, we show that DONSON scaffolds a verte...
