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

最新文章

• Measurement of α- synuclein as protein cargo in plasma extracellular vesicles AI翻译
  作者：Gilboa, Tal; Ter-Ovanesyan, Dmitry; Wang, Shih-Chin; Whiteman, Sara; Kannarkat, George T.; Church, George M.; Chen-Plotkin, Alice S.; Walt, David R.
  作者单位：Harvard University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Pennsylvania
  摘要：Extracellular vesicles (EVs) are released by all cells and hold great promise as a class of biomarkers. This promise has led to increased interest in measuring EV proteins from both total EVs as well as brain- derived EVs in plasma. However, measuring cargo proteins in EVs has been challenging because EVs are present at low levels, and EV isolation methods are imperfect at separating EVs from free proteins. Thus, knowing whether a protein measured after EV isolation is truly inside EVs is diff...
• The conformational landscape of fold- switcher KaiB is tuned to the circadian rhythm timescale AI翻译
  作者：Wayment-Steele, Hannah K.; Otten, Renee; Pitsawong, Warintra; Ojoawo, Adedolapo M.; Glaser, Andrew; Calderone, Logan A.; Kern, Dorothee
  作者单位：Brandeis University; Howard Hughes Medical Institute; Scripps Research Institute
  摘要：How can a single protein domain encode a conformational landscape with multiple stably folded states, and how do those states interconvert? Here, we use real- time and relaxation- dispersion NMR to characterize the conformational landscape of the circadian rhythm protein KaiB from Rhodobacter sphaeroides. Unique among known natural metamorphic proteins, this KaiB variant spontaneously interconverts between two monomeric states: the Ground and Fold- switched (FS) states. KaiB in its FS state in...
• Quantitative omnigenic model discovers interpretable genome-wide associations AI翻译
  作者：Ruzickova, Natalia; Hledik, Michal; Tkacik, Gasper
  作者单位：Institute of Science & Technology - Austria
  摘要：As their statistical power grows, genome-wide association studies (GWAS) have identified an increasing number of loci underlying quantitative traits of interest. These loci are scattered throughout the genome and are individually responsible only for small fractions of the total heritable trait variance. The recently proposed omnigenic model provides a conceptual framework to explain these observations by postulating that numerous distant loci contribute to each complex trait via effect propag...
• QSOX1 facilitates dormant esophageal cancer stem cells to evade immune elimination via PD-L1 upregulation and CD8 T cell exclusion AI翻译
  作者：Wei, Jia-Ru; Zhang, Baifeng; Zhang, Yu; Chen, Wo-Ming; Zhang, Xiao-Ping; Zeng, Ting-Ting; Li, Yan; Zhu, Ying-Hui; Guan, Xin-Yuan; Li, Lei
  作者单位：Sun Yat Sen University; Sun Yat Sen University; Sun Yat Sen University; University of Hong Kong; Sun Yat Sen University; State Key Lab Oncology South China; Sun Yat Sen University; Sun Yat Sen University; University of Hong Kong
  摘要：Dormant cancer stem cells (DCSCs) exhibit characteristics of chemotherapy resistance and immune escape, and they are a crucial source of tumor recurrence and metastasis. However, the underlying mechanisms remain unrevealed. We demonstrate that enriched Gzmk+ CD8+ T cells within the niche of esophageal DCSCs restrict the outgrowth of tumor mass. Nonetheless, DCSCs can escape immune elimination by enhancing PD- L1 signaling, thereby maintaining immune equilibrium. Quiescent fibroblast- derived q...
• Gut- to- brain regulation of Drosophila aging through neuropeptide F, insulin, and juvenile hormone AI翻译
  作者：Chen, Jiangtian; Nouzova, Marcela; Noriega, Fernando G.; Tatar, Marc
  作者单位：Brown University; Czech Academy of Sciences; Biology Centre of the Czech Academy of Sciences; State University System of Florida; Florida International University; State University System of Florida; Florida International University; University of South Bohemia Ceske Budejovice
  摘要：Dietary restriction (DR) slows aging in many animals, while in some cases, the sensory signals from diet alone are sufficient to retard or accelerate lifespan. The digestive tract is a candidate location to sense nutrients, where neuropeptides secreted by enteroendocrine cells (EEC) produce systemic signals in response to food. Here, we measure how Drosophila neuropeptide F (NPF) is secreted into adult circulation by EEC and find that specific EEC differentially respond to dietary sugar and ye...
• Live magnetic observation of parahydrogen hyperpolarization dynamics AI翻译
  作者：Eills, James; Mitchell, Morgan W.; Rius, Irene Marco; Tayler, Michael C. D.
  作者单位：University of Barcelona; Barcelona Institute of Science & Technology; Institut de Bioenginyeria de Catalunya; Barcelona Institute of Science & Technology; Universitat Politecnica de Catalunya; Institut de Ciencies Fotoniques (ICFO); ICREA; Helmholtz Association; Research Center Julich
  摘要：Hyperpolarized nuclear spins in molecules exhibit high magnetization that is unachievable by classical polarization techniques, making them widely used as sensors in physics, chemistry, and medicine. The state of a hyperpolarized material, however, is typically only studied indirectly and with partial destruction of magnetization, due to the nature of conventional detection by resonant-pickup NMR spectroscopy or imaging. Here, we establish atomic magnetometers with sub-pT sensitivity as an alt...
• Observing the crack tip behavior at the nanoscale during fracture of ceramics AI翻译
  作者：Gavalda-Diaz, Oriol; Emmanuel, Max; Berenov, Andrey; Marquardt, Katharina; Saiz, Eduardo; Giuliani, Finn
  作者单位：Imperial College London; University of Nottingham; University of Oxford
  摘要：Ultimately, brittle fracture involves breaking atomic bonds. However, we still lack a clear picture of what happens in the highly deformed region around a moving crack tip. Consequently, we still cannot link nanoscale phenomena with the macroscopic toughness of materials. The unsolved challenge is to observe the movement of the crack front at the nanoscale while extracting quantitative information. Here, we address this challenge by monitoring stable crack growth inside a transmission electron...
• Intensive leaf cooling promotes tree survival during a record heatwave AI翻译
  作者：Posch, Bradley C.; Bush, Susan E.; Koepke, Dan F.; Schuessler, Alexandra; Anderegg, Leander L. D.; Aparecido, Luiza M. T.; Blonder, Benjamin W.; Guo, Jessica S.; Kerr, Kelly L.; Moran, Madeline E.; Cooper, Hillary F.; Doughty, Christopher E.; Gehring, Catherine A.; Whitham, Thomas G.; Allan, Gerard J.; Hultine, Kevin R.
  作者单位：University of California System; University of California Berkeley; University of California System; University of California Santa Barbara; Utah System of Higher Education; University of Utah; University of Arizona; Arizona State University; Arizona State University-Tempe; Northern Arizona University; Northern Arizona University; Northern Arizona University
  摘要：Increasing heatwaves are threatening forest ecosystems globally. Leaf thermal regulation and tolerance are important for plant survival during heatwaves, though the interaction between these processes and water availability is unclear. Genotypes of the widely distributed foundation tree species Populusfremontii were studied in a controlled common garden during a record summer heatwave-where air temperature exceeded 48 degrees C. When water was not limiting, all genotypes cooled leaves 2 to 5 d...
• CryoSeek: A strategy for bioentity discovery using cryoelectron microscopy AI翻译
  作者：Wang, Tongtong; Li, Zhangqiang; Xu, Kui; Huang, Wenze; Huang, Gaoxingyu; Zhang, Qiangfeng Cliff; Yan, Nieng
  作者单位：Tsinghua University; Westlake University; Westlake Laboratory; Shenzhen Medical Academy of Research & Translation (SMART); Shenzhen Bay Laboratory
  摘要：Structural biology is experiencing a paradigm shift from targeted structural determination to structure- guided discovery of previously uncharacterized bioentities. We employed cryoelectron microscopy (cryo-EM) to analyze filtered water samples collected from the Tsinghua Lotus Pond. Here, we report the structural determination and characterization of two highly similar helical fibrils, named TLP-1a and TLP-1b, each approximately 8 nm in diameter with a 15- & Aring; wide tunnel. These fibrils ...
• Comprehensive stable- isotope tracing of glucose and amino acids identifies metabolic by- products and their sources in CHO cell culture AI翻译
  作者：Gonzalez, Jacqueline E.; Naik, Harnish Mukesh; Oates, Eleanor H.; Dhara, Venkata Gayatri; Mcconnell, Brian O.; Kumar, Swetha; Betenbaugh, Michael J.; Antoniewicz, Maciek R.
  作者单位：University of Delaware; Johns Hopkins University; University of Michigan System; University of Michigan
  摘要：Mammalian cell culture processes are widely utilized for biotherapeutics production, disease diagnostics, and biosensors, and hence, should be optimized to support robust cell growth and viability. However, toxic by- products accumulate in cultures due to inefficiencies in metabolic activities and nutrient utilization. In this study, we applied comprehensive 13 C stable- isotope tracing of amino acids and glucose to two Immunoglobulin G (IgG) producing Chinese Hamster Ovary (CHO) cell lines to...