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

最新文章

• Systemic in utero gene editing as a treatment for cystic fibrosis AI翻译
  作者：Ricciardi, Adele S.; Barone, Christina; Putman, Rachael; Quijano, Elias; Gupta, Anisha; Nguyen, Richard; Mandl, Hanna; Piotrowski-Daspit, Alexandra S.; Lopez-Giraldez, Francesc; Luks, Valerie; Freedman-Weiss, Mollie R.; Farrelly, James; Ahle, Samantha; Lynn, Anna Y.; Glazer, Peter M.; Saltzman, W. Mark; Stitelman, David H.; Egan, Marie E.
  作者单位：Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University
  摘要：In utero gene editing has the potential to modify disease- causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. In cystic fibrosis (CF), a disease that arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. Thus, treating CF...
• Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling (vol 113, pg E3773, 2016) AI翻译
  作者：Yin, Yaling; Gao, Di; Wang, Yali; Wang, Zhi-Hao; Wang, Xin; Ye, Jinwang; Wu, Dongqin; Fang, Lin; Pi, Guilin; Yang, Ying; Wang, Xiao-Chuan; Lu, Chengbiao; Ye, Keqiang; Wang, Jian-Zhi
• Induction of a neurotoxin in diatoms by iron limitation via cysteine synthase AI翻译
  作者：Zheng, Xianyao; Wu, Shuaishuai; Qiu, Jiangbing; Li, Aifeng; Li, Ling; Yan, Guowang; Li, Min; Meng, Fanping; Zhang, Kaidian; Lin, Senjie
  作者单位：Hainan University; Ocean University of China; Ocean University of China; Xiamen University; University of Connecticut
  摘要：The beta- N- methylamino- L- alanine (BMAA) is an emerging neurotoxin associated with human neurodegenerative diseases such as Alzheimer's disease. Here, we report the prevalence of BMAA synthesis in protein forms by marine diatoms and reconstruct its tentative biosynthesis pathway. Remarkably, the BMAA production is strongly induced by iron limitation. Transcriptomic analyses suggest that cysteine synthase (CysK) is involved in BMAA synthesis. This is verified as CRISPR/Cas9- based CysK knock...
• Quantum oscillations in the hole-doped cuprates and the confinement of spinons (vol 121, e2418633121, 2024) AI翻译
  作者：Bonetti, Pietro M.; Christos, Maine; Sachdev, Subir
• Longitudinal associations between birth- to- six cortical growth and childhood neurocognitive function AI翻译
  作者：Davis, Megan M.; Woodburn, Mackenzie; Nugiel, Tehila; Rakesh, Divyangana; Tate, Maresa; Asciutto, William; Lin, Weili; Cohen, Jessica R.; Sheridan, Margaret A.
  作者单位：University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; State University System of Florida; Florida State University; University of London; King's College London; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine
  摘要：The human cortex undergoes immense change in the first years of life, doubling in thickness within the first year and evidencing the greatest change within the first 5 y. While substantial research has identified the early postnatal period as a sensitive period in cortical development, research to date lacks the temporal resolution necessary to identify which aspects of cortical change predict later neural and cognitive function. This study leveraged a rich longitudinal dataset of cortical thi...
• Formation of giant ER sheets by pentadecanoic acid causes lipotoxicity in fission yeast AI翻译
  作者：Hoshikawa, Yojiro; Shirota, Natsuho; Tsugawa, Hiroshi; Kimura, Satoshi; Matsuyama, Akihisa; Yashiroda, Yoko; Kakeya, Hideaki; Arita, Makoto; Iizumi, Reiko; Yoshida, Minoru; Nishimura, Shinichi
  作者单位：University of Tokyo; Hiroshima University; Hiroshima University; RIKEN; RIKEN; Yokohama City University; Tokyo University of Agriculture & Technology; University of Tokyo; RIKEN; Kyoto University; Keio University; Keio University; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Tokyo; University of Tokyo; RIKEN
  摘要：Excess amounts of saturated fatty acids (FAs) are toxic to organisms, a condition termed lipotoxicity, which is often accompanied by pleiotropic cellular and tissue dysfunction. Here, we show that pentadecanoic acid (C15:0) exerts toxicity on the fission yeast Schizosaccharomyces pombe by generating an aberrantly planar endoplasmic reticulum (ER) structure, which we named a giant ER sheet. Untargeted lipidomics revealed that C15:0 is incorporated into complex lipids depending on an acyl- CoA l...
• Cardiolipin membranes drive Myosin VI activation, oligomerization, and processive cargo transport AI翻译
  作者：Montanarella, Antonino F.; Hundt, Nikolas; Keim, Dominik; Venczel, Aron; Zierhut, Felix; Langnickel, Simon; Graw, Andreas; Kroess, Markus; Dietrich, Johannes; Saczko, Dario; Veigel, Claudia
  作者单位：University of Munich; University of Munich
  摘要：Mitochondrial damage determines cell fate, leading to mitochondrial autophagy or cellular apoptosis in health and disease. The molecular mechanisms and role of the acto-myosin cytoskeleton regulating mitochondrial clearance and membrane remodeling are critical in neurodegenerative disease progression including Alzheimer, but remain unclear. To investigate the potential link between full-length Myosin VI (FL-Myo6) recruitment and exposure of the mitochondria-specific lipid cardiolipin (CL), her...
• A direct computational assessment of vinculin-actin unbinding kinetics reveals catch-bonding behavior AI翻译
  作者：Ccoa, Willmor J. Pena; Mukadum, Fatemah; Ramon, Aubin; Stirnemann, Guillaume; Hocky, Glen M.
  作者单位：New York University; University of Cambridge; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Ecole Normale Superieure (ENS); New York University
  摘要：Vinculin forms a catch bond with the cytoskeletal polymer actin, displaying an increased bond lifetime upon force application. Notably, this behavior depends on the direction of the applied force, which has significant implications for cellular mechanotransduction. In this work, we present a comprehensive molecular dynamics simulation study, employing enhanced sampling techniques to investigate the thermodynamic, kinetic, and mechanistic aspects of this phenomenon at physiologically relevant f...
• The distribution of highly deleterious variants across human ancestry groups AI翻译
  作者：Stolyarova, Anastasia; Coop, Graham; Przeworski, Molly
  作者单位：Columbia University; University of California System; University of California Davis; University of California System; University of California Davis; Columbia University
  摘要：A major focus of human genetics is to map severe disease mutations. Increasingly, that goal is understood as requiring huge numbers of people to be sequenced from every broadly defined genetic ancestry group, so as not to miss ancestry- specific variants. Here, we consider whether this focus is warranted. We start from first principles considerations, based on models of mutation-drift- selection balance, which suggest that since severe disease mutations tend to be strongly deleterious, and thu...
• Dinucleotide preferences underlie apparent codon preference reversals in the Drosophila melanogaster lineage AI翻译
  作者：Yamashita, Haruka; Matsumoto, Tomotaka; Kawashima, Kent; Daanaa, Hassan Sibroe Abdulla; Yang, Ziheng; Akashi, Hiroshi
  作者单位：Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; Graduate University for Advanced Studies - Japan; University of London; University College London; Graduate University for Advanced Studies - Japan
  摘要：We employ fine-scale population genetic analyses to reveal dynamics among interacting forces that act at synonymous sites and introns among closely related Drosophila cies. Synonymous codon usage bias has proven to be well suited for population genetic inference. Under major codon preference (MCP), translationally superior major codons confer fitness benefits relative to their less efficiently and/or accurately decoded synonymous counterparts. Our codon family and lineage-specific analyses exp...