33期

最新文章

• The history of enzyme evolution embedded in metabolism AI翻译
  作者：Corlett, Tatsuya; Smith, Harrison B.; Smith, Eric; Goldford, Joshua E.; Longo, Liam M.
  作者单位：Institute of Science Tokyo; University System of Georgia; Georgia Institute of Technology; California Institute of Technology
  摘要：Whereas phylogenetic reconstructions are a primary record of protein evolution, it is unknown whether the deep history of enzymes is encoded at higher levels of biological organization. Here, we demonstrate that the emergence and reuse history of enzymatic folds is embedded within the web of metabolite-cofactor-enzyme interdependencies that comprise biosphere-scale metabolic reaction networks. Using a simple network analysis approach, we reconstruct the relative ordering of enzymatic fold emer...
• Single-cell multiomics identifies an ALDH9A1-carnitine signaling axis driving resistance of NSCLC to immunotherapy AI翻译
  作者：Du, Hailei; Lang, Tong; Zha, Xiaoxue; Qu, Chao; Chen, Ling; Yao, Shihua; Feng, Xing; Jin, Zhaohui
  作者单位：Shanghai Jiao Tong University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Jilin University; Jilin University; Shanghai Jiao Tong University; Naval Medical University; Yale University; Yale University; Sichuan University
  摘要：Immunotherapy resistance remains a major barrier to achieving sustained patient improvement in non-small cell lung cancer (NSCLCs). Here, through integrating CODEX, metabolomics, CyTOF, ATAC-seq, and single-cell spatial transcriptomics from NSCLC tumors, we uncover an unrecognized role of ALDH9A1 in promoting resistance to anti-PD-1 therapy. In immunocompetent, but not immunocompromised mouse models, loss of ALDH9A1 markedly restrains tumor growth. This effect is accompanied by increased matur...
• Selective loss of primary cilia and neurotrophic signaling in G51D α-synuclein mice highlights a common pathway to Parkinson's disease AI翻译
  作者：Lin, Yu-En; Jaimon, Ebsy; Kim, YoungDoo; Loftman, Annabeth; Vijayakumaran, Aaran; Belfort, Benjamin D. W.; Chiang, Claire Y.; Arenkiel, Benjamin R.; Zoghbi, Huda Y.; Pfeffer, Suzanne R.
  作者单位：Stanford University; Baylor College of Medicine; Baylor College Medical Hospital
  摘要：Parkinson's disease is characterized by dopaminergic neuron loss and accumulation of alpha-synuclein aggregates in the brain. G51D alpha-synuclein knock-in mice provide a genetically and clinically relevant model of disease, exhibiting early olfactory deficits, age-dependent motor impairment, and progressive phospho-alpha-synuclein accumulation. In multiple Parkinson's disease models, striatal cholinergic and parvalbumin interneurons, as well as astrocytes, lose primary cilia and the neurotrop...
• Mechanistic insights into cooperative permeation of glycerol and water through human aquaporin-10 AI翻译
  作者：Rai, Kunal; Joshi, Himanshu
  作者单位：Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Hyderabad; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Hyderabad
  摘要：Human aquaporins are integral membrane proteins that facilitate transmembrane transport of small molecules. Among the 13 members of this family, pH-regulated human aquaporin-10 (hAQP10) plays a critical role in glycerol metabolism and lipid homeostasis. A molecular-level understanding of water and glycerol transport through hAQP10 nanopores is essential for enabling rational therapeutic interventions. We present an all-atom molecular dynamics (MD) simulation study characterizing the nanoscale ...
• Illegal markets for cigarettes and e-cigarettes AI翻译
  作者：Kenkel, Donald; Phillips, Grace
  作者单位：Cornell University; University of Memphis
  摘要：This paper discusses the long-standing illegal markets for cigarettes and the more recently emerged illegal markets for e-cigarettes. We identify three distinctive market fundamentals that help explain many features of the illegal markets. First, in contrast to some illegal goods, many countries have sizable legal markets for cigarettes and e-cigarettes alongside the illegal markets. In 2024, tobacco products generated almost $1 trillion in revenues; e-cigarettes generated $26 billion dollars....
• Scientific production in the era of large language models: Outcome-triggered treatment timing and spurious event-study dynamics AI翻译
  作者：Renault, Thomas; Bergeaud, Antonin; Bosquet, Clement
  作者单位：Universite Paris Saclay; Hautes Etudes Commerciales (HEC) Paris
  摘要：Large language models (LLMs) are increasingly used in scientific writing, but their effect on individual productivity is difficult to identify because adoption is rarely directly observed. [K. Kusumegi et al., Science 390, 1240-1243 (2025)] infer adoption from the first paper detected as LLM-assisted and report large productivity gains after adoption. We show that this treatment-timing rule mechanically generates positive event-study dynamics even in the absence of any causal effect. Because h...
• Emergence of biosignatures on Earth and implications for life detection AI翻译
  作者：Barge, Laura M.; Eigenbrode, Jennifer L.; Fournier, Gregory; Theiling, Bethany
  作者单位：California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Massachusetts Institute of Technology (MIT)
  摘要：Earth's organic chemical evolution (OCE) from abiotic to prebiotic to biotic provides critical insights that may have implications for how we interpret observations made by life-detection planetary missions. To search for life on other worlds, astrobiologists seek biosignatures: features that indicate the presence of extant or extinct life as we know it. However, because the age of putative extraterrestrial biospheres is unknown, biosignatures present at or shortly after life's emergence may h...
• A tonsil organoid model reveals Epstein-Barr virus-infected germinal center B cell states during primary infection AI翻译
  作者：Mitul, Mahina Tabassum; Sun, Yizhe; Yates, Timothy B.; Sureshchandra, Suhas; Kastenschmidt, Jenna M.; Sorn, Andrew M.; Wagoner, Zachary W.; Joloya, Erika M.; Nair, Arjun K.; Daugherty, Allyssa; Saligrama, Naresha; Ahuja, Gurpreet; Zhong, Qiu; Trask, Douglas; Forney, Carmy; Guo, Rui; Weirauch, Matthew T.; Kottyan, Leah C.; Gewurz, Benjamin E.; Wagar, Lisa E.
  作者单位：University of California System; University of California Irvine; University of California System; University of California Irvine; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Washington University (WUSTL); Saint Louis University; University of California System; University of California Irvine; Cincinnati Children's Hospital Medical Center
  摘要：Epstein-Barr virus (EBV) colonizes secondary lymphoid tissues to establish persistent infection and is strongly associated with malignancy and autoimmunity. Our understanding of EBV infection biology is hindered by a lack of models that capture infected B cell activity in the lymphoid tissue microenvironment. We therefore developed an EBV human tonsil organoid model to evaluate key B cell states and antiviral responses, including after primary infection. EBV promoted B cell differentiation int...
• Structure and dynamics of confined water in amyloid protein fibril nanochannels AI翻译
  作者：Mon, Fiona; Abraham, Conor B.; Straub, John E.
  作者单位：Boston University
  摘要：Many fibrils of amyloid proteins are characterized by a dense core structure that largely excludes water. However, an increasing number of amyloid fibril structures are observed to contain water channels. Although water in membrane protein channels and pores has been studied, the structure and dynamics of water in amyloid protein fibril nanochannels is largely unexplored. In this computational study, we used molecular dynamics simulations to characterize the structure and dynamics of water ins...
• A phosphorylation switch governs KIF11's mechanical output during mitosis AI翻译
  作者：Semic, Amila; Reddy, Babu J. N.; Muretta, Joseph M.; Vandal, Sarah E.; Thompson, Alex F.; Fonseca, Cindy L.; Rosenfeld, Steven S.; Gross, Steven P.; Stumpff, Jason
  作者单位：University of Vermont; University of California System; University of California Irvine; University of California System; University of California Irvine; University of Minnesota System; University of Minnesota Twin Cities; Mayo Clinic; University of California System; University of California Irvine
  摘要：The kinesin-5 motor protein KIF11 is crucial for mitotic spindle assembly, driving the separation of spindle poles through microtubule sliding. Src-family kinases phosphorylate KIF11 at multiple tyrosine residues within its motor domain, but the mechanistic consequences of these modifications remain unclear. Here, we dissect the role of phosphorylation at Y211 using phospho-mimetic (Y211E) and nonphosphorylatable mutants (Y211F) in biochemical, biophysical, and cellular assays. Optical trappin...