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

最新文章

• Environmental resistome-guided development of resistance-tolerant antibiotics AI翻译
  作者：Peek, James; Bhattacharjee, Abir; Burian, Jan; Hsieh, David Chun- Cheng; Hernandez, Yozen; Ternei, Melinda; Panfil, Cecilia; Brady, Sean F.
  作者单位：Rockefeller University; Rockefeller University
  摘要：Failure to anticipate new forms of antibiotic resistance has led to resistance developing rapidly to virtually all antibiotics that have entered clinical use. Many of the most problematic types of resistance originated in the environment, where ancient arms races between antibiotic-producing microbes and their competitors have created vast arsenals of antibiotics and resistance. Seizing on the knowledge that resistance in nature is frequently a harbinger of future clinical resistance, we propo...
• Cross-feeding creates tipping points in microbiome diversity AI翻译
  作者：Clegg, Tom; Gross, Thilo
  作者单位：Carl von Ossietzky Universitat Oldenburg; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; Carl von Ossietzky Universitat Oldenburg
  摘要：A key unresolved question in microbial ecology is how the extraordinary diversity of microbiomes emerges from the interactions among their many functionally distinct populations. This process is driven in part by the cross-feeding networks that help to structure these systems, in which consumers use resources to fuel their metabolism, creating by-products which can be used by others in the community. Understanding the effects of cross-feeding presents a major challenge, as it creates complex i...
• Caveolin assemblies displace one bilayer leaflet to organize and bend membranes AI翻译
  作者：Doktorova, Milka; Daum, Sebastian; Reagle, Tyler R.; Cannon, Hannah I.; Ebenhan, Jan; Neudorf, Sarah; Han, Bing; Sharma, Satyan; Kasson, Peter; Levental, Kandice R.; Bacia, Kirsten; Kenworthy, Anne K.; Levental, Ilya
  作者单位：University of Virginia; Stockholm University; Martin Luther University Halle Wittenberg; Uppsala University; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology
  摘要：Caveolin is a monotopic integral membrane protein, widely expressed in metazoans and responsible for constructing enigmatic membrane invaginations known as caveolae. Recently, the high-resolution structure of a purified human caveolin assembly, the CAV1-8S complex, revealed a unique organization of 11 protomers arranged in a tightly packed, radially symmetric spiral disc. One face and the outer rim of this disc are hydrophobic, suggesting that the complex incorporates into membranes by displac...
• The oncoprotein SET promotes serine-derived one-carbon metabolism by regulating SHMT2 enzymatic activity AI翻译
  作者：Jiao, Zishan; Zhang, Mi; Ning, Jingyuan; Yao, Han; Yan, Xiaojun; Wu, Zhen; Wu, Dexuan; Liu, Yajing; Zhang, Meng; Wang, Lin; Wang, Donglai
  作者单位：Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; China Medical University; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College
  摘要：Cancer cells frequently reprogram one-carbon metabolic pathways to fulfill their vigorous demands of biosynthesis and antioxidant defense for survival and proliferation. Dysfunction of oncogenes or tumor suppressor genes is critically involved in this process, but the precise mechanisms by which cancer cells actively trigger one-carbon metabolic alterations remain incompletely elucidated. Here, by using untargeted metabolomic analysis, we identify the oncoprotein SE translocation (SET) as a ke...
• Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine AI翻译
  作者：Maciag, Anna E.; Yang, Yue; Sharma, Alok K.; Turner, David M.; Dehart, Caroline J.; Abdelkarim, Hazem; Fan, Lixin; Smith, Brian P.; Kumari, Vandana; Dyba, Marcin; Rigby, Megan; Badillo, Jean A. Castillo; Adams, Lauren; Fornelli, Luca; Fox, Stephen; Brafman, Alla; Turbyville, Thomas; Gillette, William; Messing, Simon; Agamasu, Constance; Wolfe, Andrew L.; Gysin, Stephan; Chan, Albert H.; Simanshu, Dhirendra K.; Esposito, Dominic; Chertov, Oleg; Stephen, Andrew G.; Arkin, Michelle; Renslo, Adam; Kelleher, Neil L.; Gaponenko, Vadim; Lightstone, Felice C.; Nissley, Dwight, V; McCormick, Frank
  作者单位：National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Northwestern University; Northwestern University; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of California System; University of California San Francisco; Northwestern University; Northwestern University; Northwestern University
  摘要：RAS is the most frequently mutated oncogene in cancer. RAS proteins show high sequence similarities in their G-domains but are significantly different in their C-terminal hyper-variable regions (HVR). These regions interact with the cell membrane via lipid anchors that result from posttranslational modifications (PTM) of cysteine residues. KRAS4b is unique as it has only one cysteine that undergoes PTM, C185. Small molecule covalent modification of C185 would block any form of prenylation and ...
• Structural basis for substrate selectivity by site- one protease revealed by studies with a small- molecule inhibitor AI翻译
  作者：Bullington, Ashley, V; Micallo, Ilaria; Bajaj, Bilkish; Kumar, Pankaj; Schlamowitz, Netanya; Silva, Aurora; Hendrix, Sebastian; Zelcer, Noam; Kober, Daniel L.
  作者单位：University of Texas System; University of Texas Southwestern Medical Center; University of Amsterdam
  摘要：Site-one protease (S1P) carries out the first proteolytic step to activate membrane-bound effector proteins in the Golgi. S1P matures through an autocatalytic process that begins in the endoplasmic reticulum (ER) and culminates with the displacement of its inhibitory pro-domain by its cofactor, sterol regulatory element binding protein-regulating gene (SPRING). Spatial control of S1P activity and substrate localization underpins signaling pathways governing, among others, lipogenesis, ER stres...
• Exposing the role of individual heterogeneity in bighorn sheep population dynamics AI翻译
  作者：Forsythe, Amy B.
  作者单位：University of British Columbia; University of British Columbia
• Bounded dissipation law and profiles of turbulent velocity moments in wall flows AI翻译
  作者：Chen, Xi; Sreenivasan, Katepalli R.
  作者单位：Beihang University; New York University; New York University Tandon School of Engineering
  摘要：Understanding the effects of solid boundaries on turbulent fluctuations remains a longstanding challenge. Available data on mean-square fluctuations in these flows show apparent contradiction with classical scaling. We had earlier proposed an alternative model based on the principle of bounded dissipation. Despite its putative success, a conclusive outcome requires much higher Reynolds numbers than are available at present, or can be expected to be available in the near future. However, the mo...
• Phospholipid flippase ATP11A brokers uterine epithelial integrity and function AI翻译
  作者：Krala, Alexa; Tsolova, Aleksandra O.; Radford, Bethany N.; Jadli, Anshul S.; Zhao, Xiang; Blackwell, Danielle; Narang, Ankita; Dean, Wendy; Hemberger, Myriam
  作者单位：University of Calgary; University of Calgary; University of Calgary
  摘要：Uterine adaptations driven by the steroid hormones estrogen and progesterone are pivotal for embryo implantation and, ultimately, for a successful pregnancy. Here, we show in mice that genetic ablation of the membrane lipid flippase Atp11a causes severe deficits in this hormonal response and profound defects in the morphological organization and transcriptional profile of the uterine epithelial compartment where Atp11a is expressed. Atp11a-null uterine epithelial cells lack tight junctions, an...
• Mechanism of allosteric activation in human mitochondrial ClpP protease AI翻译
  作者：Goncalves, Monica M.; Uday, Adwaith B.; Forrester, Taylor J. B.; Currie, S. Quinn W.; Kim, Angelina S.; Feng, Yue; Jitkova, Yulia; Velyvis, Algirdas; Harkness, Robert W.; Kimber, Matthew S.; Schimmer, Aaron D.; Zeytuni, Natalie; Vahidi, Siavash
  作者单位：University of Guelph; McGill University; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; McGill University
  摘要：Human ClpP protease contributes to mitochondrial protein quality control by degrading misfolded proteins. ClpP is overexpressed in cancers such as acute myeloid leukemia (AML), where its inhibition leads to the accumulation of damaged respiratory chain subunits and cell death. Conversely, hyperactivating ClpP with small- molecule activators, such as the recently discovered ONC201, disrupts mitochondrial protein degradation and impairs respiration in cancer cells. Despite its critical role in h...