Proceedings of the National Academy of Sciences of the United States of America

最新文章

• Dynamic relocation of PKA regulatory subunits during sperm capacitation: Linking PKA to the CatSper signaling complex AI翻译
  作者：Novero, Analia G.; Volante, Arturo Matamoros -; Gomez -Olivieri, Lucila R.; Stival, Cintia; Luque, Guillermina M.; Szalai, Alan M.; Ambrosio, Andrea L.; Stefani, Fernando D.; Buffone, Mariano G.; Krapf, Dario; Krapf, Diego
  作者单位：National University of Rosario; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); National University of Rosario; Colorado State University System; Colorado State University Fort Collins; Colorado State University System; Colorado State University Fort Collins; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Colorado State University System; Colorado State University Fort Collins; University of Buenos Aires
  摘要：To fertilize an oocyte, mammalian spermatozoa must undergo a maturation step known as capacitation that takes place after ejaculation. Protein kinase A (PKA) plays a fundamental role in capacitation in all mammalian species. Before capacitation, PKA is maintained in an inactive state where the catalytic subunits are bound to a dimer of inhibitory regulatory subunits. A key element in the regulation of PKA lies in its intracellular compartmentalization achieved by docking at A-kinase anchoring ...
• The cell-permeable iron chelator M606 inhibits MYCN-driven neuroblastoma via an E2F3-mediated response AI翻译
  作者：Pandher, Ruby; Xue, Chengyuan; Gamble, Laura D.; Milazzo, Giorgio; Di Giacomo, Simone; Murray, Jayne; Cheung, Leanna; Ferrucci, Francesca; Palombo, Marta; Purgato, Stefania; Burkhart, Catherine A.; Fedtsova, Natalia; Gleiberman, Anatoli S.; Purmal, Andrei A.; Korotchkina, Lioubov; Nikiforov, Mikhail A.; Makarov, Sergei S.; Telfer, Thomas J.; Codd, Rachel; Marshall, Glenn M.; Scott, David A.; Osterman, Andrei L.; Gudkov, Andrei, V; Perini, Giovanni; Haber, Michelle; Norris, Murray D.
  作者单位：Children's Cancer Institute; University of New South Wales Sydney; University of Bologna; Roswell Park Comprehensive Cancer Center; University of Sydney; NSW Health; Sydney Childrens Hospitals Network; University of Sydney; Sanford Burnham Prebys Medical Discovery Institute; University of New South Wales Sydney
  摘要：Despite Myc oncoproteins being major causal factors in human cancer, they remain undruggable. The MYCN oncogene is one of the most powerful prognostic markers for the childhood cancer neuroblastoma and represents an important target for developing novel therapeutics. Here, we report the finding and characterization of M606, a selective small molecule inhibitor of MYCN, which was identified by screening a diverse chemical library. M606 reduced MYCN protein levels in neuroblastoma cell lines and...
• Controlling DNA-RNA strand displacement kinetics with base distribution AI翻译
  作者：Ratajczyk, Eryk J.; Bath, Jonathan; Sulc, Petr; Doye, Jonathan P. K.; Louis, Ard A.; Turberfield, Andrew J.
  作者单位：University of Oxford; University of Oxford; University of Oxford; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; Arizona State University; Arizona State University-Tempe; Technical University of Munich; University of Oxford
  摘要：DNA-RNA hybrid strand displacement underpins the function of many natural and engineered systems. Understanding and controlling factors affecting DNA-RNA strand displacement reactions is necessary to enable control of processes such as CRISPR-Cas9 gene editing. By combining multiscale modeling with strand displacement experiments, we show that the distribution of bases within the displacement domain has a very strong effect on reaction kinetics, a feature unique to DNA-RNA hybrid strand displa...
• Programmable seconds- to- days- long delayed snapping in jumping metashells AI翻译
  作者：Qing, Haitao; Zhou, Caizhi; Qi, Fangjie; Yin, Jie
  作者单位：North Carolina State University
  摘要：Shape- shifting structures can transform and recover their shapes in response to external stimuli, but they often lack programmable, clock- like control over spatiotemporal deformation and motion, especially after stimuli are removed. Achieving autonomous, time- regulated spatiotemporal motion remains a grand challenge. Here, we present an autonomous delayed- jumping metashell that integrates viscoelastic materials with monostable architected structures to address this limitation. The metashel...
• The cellular dance that splits vessels AI翻译
  作者：Munn, Lance L.
  作者单位：Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
• Task difficulty modulates the effect of mind wandering on phase dynamics AI翻译
  作者：Long, Zhengkun; Northoff, Georg; Fu, Xiaolan
  作者单位：Chinese Academy of Sciences; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shenzhen University; University of Ottawa; Shanghai Jiao Tong University
  摘要：Mind wandering attenuates widespread sensory and motor processing, both of which are mediated by phase coherence. However, it remains unclear i) whether mind wandering impacts both sensory input and motor output processing by modulating ii) neural entrainment to external stimuli, as measured by intertrial phase coherence (ITPC), and specifically iii) whether task difficulty with different degrees of attentional demands moderates the impact of mind wandering on phase coherence. Using the though...
• Biochemical and structural basis of Dicer helicase function unveiled by resurrecting ancient proteins AI翻译
  作者：Aderounmu, Adedeji M.; Maus-Conn, Josephine; Consalvo, Claudia D.; Shen, Peter S.; Bass, Brenda L.
  作者单位：Utah System of Higher Education; University of Utah
  摘要：A fully functional Dicer helicase, present in the modern arthropod, uses energy from ATP hydrolysis to power translocation on bound dsRNA, enabling the processive dsRNA cleavage required for efficient antiviral defense. However, modern Dicer orthologs exhibit divergent helicase functions that affect their ability to contribute to antiviral defense. Moreover, mechanisms that couple ATP hydrolysis to Dicer helicase movement on dsRNA remain enigmatic. We used biochemical and structural analyses o...
• Calcineurin controls the cytokinesis machinery during thermal stress in Cryptococcus deneoformans AI翻译
  作者：Yadav, Vikas; Averette, Anna Floyd; Upadhya, Rajendra; Heitman, Joseph
  作者单位：Duke University
  摘要：Calcineurin is a highly conserved phosphatase that plays a central role in sensing calcium and governing transcriptional, posttranscriptional, and posttranslational signaling networks. Calcineurin is a heterodimer consisting of a catalytic A subunit and a regulatory B subunit. Through downstream effectors, calcineurin signaling drives myriad responses in different organisms. In the fungal pathogenic Cryptococcus species complex that infects humans, calcineurin governs thermotolerance and is es...
• Learning to estimate sample-specific transcriptional networks for 7,000 tumors AI翻译
  作者：Ellington, Caleb N.; Lengerich, Benjamin J.; Watkins, Thomas B. K.; Yang, Jiekun; Adduri, Abhinav K.; Mahbub, Sazan; Xiao, Hanxi; Kellis, Manolis; Xing, Eric P.
  作者单位：Carnegie Mellon University; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of London; University College London; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Mohamed bin Zayed University of Artificial Intelligence MBZUAI
  摘要：Cancers are shaped by somatic mutations, microenvironment, and patient background, each altering gene expression and regulation in complex ways, resulting in heterogeneous cellular states and dynamics. Inferring gene regulatory networks (GRNs) from expression data can help characterize this regulation-driven heterogeneity, but network inference requires many statistical samples, limiting GRNs to cluster-level analyses that ignore intracluster heterogeneity. We propose to move beyond coarse ana...
• Activation dynamics of ubiquitin-specific protease 7 AI翻译
  作者：Valles, Gabrielle J.; Korchak, Emilie J.; Buehre, Dane H. Geddes -; Jaiswal, Nancy; Korzhnev, Dmitry M.; Bezsonova, Irina
  作者单位：University of Connecticut; Indiana University System; Indiana University Bloomington
  摘要：Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that plays a crucial role in cellular processes, including the maintenance of genome stability and regulation of antiviral and immune responses. Its dysfunction is linked to various cancers and neurodevelopmental disorders such as Hao-Fountain syndrome. Unlike other USP-family enzymes, the triad of catalytic residues in USP7 adopts an inactive conformation and undergoes rearrangement into the active state upon substrate binding....