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

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• The limitation of lipidation: Conversion of semaglutide from once-weekly to once-monthly dosing AI翻译
  作者：Schneider, Eric L.; Hangasky, John A.; Fernandez, Rocio del Valle; Ashley, Gary W.; Santi, Daniel, V
  作者单位：University of California System; University of California San Francisco
  摘要：The objective of this work was to develop a long-acting form of the lipidated peptide semaglutide that can be administered to humans once-monthly. Semaglutide was attached to hydrogel microspheres by a cleavable linker with an expected in vivo release half-life of about 1 mo. After a single subcutaneous dose, the pharmacokinetic parameters of released semaglutide and bodyweight loss were determined in mice, and results were used to estimate the dosing and pharmacokinetics of the released semag...
• Calcineurin- fusion facilitates cryo- EM structure determination of a Family A GPCR AI翻译
  作者：Xu, Jun; Chen, Geng; Wang, Haoqing; Cao, Sheng; Heng, Jie; Deupi, Xavier; Du, Yang; Kobilka, Brian K.
  作者单位：Stanford University; The Chinese University of Hong Kong, Shenzhen; Tsinghua University; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Institute of Bioinformatics
  摘要：Advances in singe- particle cryo- electron microscopy (cryo-EM) have made it possible to solve the structures of numerous FamilyA and Family B G protein- coupled receptors (GPCRs) in complex with G proteins and arrestins, as well as several Family C GPCRs. Determination of these structures has been facilitated by the presence of large extramembrane components (such as G protein, arrestin, or Venus flytrap domains) in these complexes that aid in particle alignment during the processing of the c...
• Forecasting Africa's fertility decline by female education groups AI翻译
  作者：Adhikari, Saroja; Lutz, Wolfgang; Kebede, Endale
  作者单位：Max Planck Society; Shanghai University; Austrian Academy of Sciences; University of Vienna; University of Vienna
  摘要：While female education has long been recognized as a key driver of fertility decline during the process of demographic transition and most population projection models consider it implicitly or explicitly in their forecasts of overall fertility, there still is need for a method to forecast education-specific fertility trends directly. Here we propose a method for projecting education-specific fertility declines for cohorts of women in Sub-Saharan Africa based on all available demographic and h...
• Measuring diversity in Hollywood through the large-scale computational analysis of film AI翻译
  作者：Bamman, David; Samberg, Rachael; So, Richard Jean; Zhou, Naitian
  作者单位：University of California System; University of California Berkeley; University of California System; University of California Berkeley; McGill University
  摘要：Movies are a massively popular and influential form of media, but their computational study at scale has largely been off-limits to researchers in the United States due to the Digital Millennium Copyright Act. In this work, we illustrate use of a new regulatory framework to enable computational research on film that permits circumvention of technological protection measures on digital video discs (DVDs). We use this exemption to legally digitize a collection of 2,307 films representing the top...
• Small RNA OxyS induces resistance to aminoglycosides during oxidative stress by controlling Fe-S cluster biogenesis in Escherichia coli AI翻译
  作者：Baussier, Corentin; Oriol, Charlotte; Durand, Sylvain; Py, Beatrice; Mandin, Pierre
  作者单位：Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB)
  摘要：Fe-S clusters are essential cofactors involved in many reactions across all domains of life. Their biogenesis in Escherichia coli and other enterobacteria involves two machineries: Isc and Suf. Under conditions where cells operate with the Suf system, such as during oxidative stress or iron limitation, the entry of aminoglycosides is reduced, leading to resistance to these antibiotics. The transition between Isc and Suf machineries is controlled by the transcriptional regulator IscR. Here, we ...
• The Warburg Effect is the result of faster ATP production by glycolysis than respiration AI翻译
  作者：Kukurugya, Matthew A.; Rosset, Saharon; V. Titov, Denis
  作者单位：University of California System; University of California Berkeley; University of California System; University of California Berkeley; Tel Aviv University; University of California System; University of California Berkeley
  摘要：Many prokaryotic and eukaryotic cells metabolize glucose to organism- specific by- products instead of fully oxidizing it to carbon dioxide and water-a phenomenon referred to as the Warburg Effect. The benefit to a cell is not fully understood, given that partial metabolism of glucose yields an order of magnitude less adenosine triphosphate (ATP) per molecule of glucose than complete oxidation. Here, we test a previously formulated hypothesis that the benefit of the Warburg Effect is to increa...
• Tuning porosity of macroporous hydrogels enables rapid rates of stress relaxation and promotes cell expansion and migration AI翻译
  作者：Nerger, Bryan A.; Kashyap, Kirti; Deveney, Brendan T.; Lou, Junzhe; Hanan, Blake F.; Liu, Qi; Khalil, Andrew; Lungjangwa, Tenzin; Cheriyan, Maria; Gupta, Anupam; Jaenisch, Rudolf; Weitz, David A.; Mahadevan, L.; Mooney, David J.
  作者单位：Harvard University; Harvard University; Indian Institute of Technology System (IIT System); Indian Institute of Technology (IIT) - Hyderabad; Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University
  摘要：Extracellular matrix (ECM) viscoelasticity broadly regulates cell behavior. While hydrogels can approximate the viscoelasticity of native ECM, it remains challenging to recapitulate the rapid stress relaxation observed in many tissues without limiting the mechanical stability of the hydrogel. Here, we develop macroporous alginate hydrogels that have an order of magnitude increase in the rate of stress relaxation as compared to bulk hydrogels. The increased rate of stress relaxation occurs acro...
• Distributed feather-inspired flow control mitigates stall and expands flight envelope AI翻译
  作者：Sedky, Girguis; Simon, Nathaniel; Othman, Ahmed K.; Wiswell, Hannah; Wissa, Aimy
  作者单位：Princeton University
  摘要：Multiple rows of feathers, known as the covert feathers, contour the upper and lower surfaces of bird wings. These feathers have been observed to deploy passively during high angle of attack maneuvers and are suggested to play an aerodynamic role. However, there have been limited attempts to capture their underlying flow physics or assess the function of multiple covert rows. Here, we first identify two flow control mechanisms associated with a single covert-inspired flap and their location se...
• Heat waves may trigger unexpected surge in aerosol and ozone precursor emissions from sedges in urban landscapes AI翻译
  作者：Wang, Hui; Nagalingam, Sanjeevi; Welch, Allison M.; Leong, Christopher; Czimczik, C. I.; Guenther, Alex B.
  作者单位：University of California System; University of California Irvine
  摘要：Biogenic isoprene emissions from herbaceous plants are generally lower than those from trees. However, our study finds widespread isoprene emission in herbaceous sedge plants, with a stronger temperature response surpassing current tree- derived models. We measured and compared isoprene emissions from sedges grown in different climatic zones, all showing an exponential temperature response with a Q10 range of 7.2 to 12, significantly higher than the Q10 of about 3 for other common isoprene emi...
• 2.6-Å resolution cryo-EM structure of a class Ia ribonucleotide reductase trapped with mechanism-based inhibitor N3CDP AI翻译
  作者：Westmoreland, Dana E.; Feliciano, Patricia R.; Kang, Gyunghoon; Cui, Chang; Kim, Albert; Stubbe, Joanne; Nocera, Daniel G.; Drennan, Catherine L.
  作者单位：Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University
  摘要：Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides using radical-based chemistry. For class Ia RNRs, the radical species is stored in a separate subunit (beta 2) from the subunit housing the active site (alpha 2), requiring the formation of a short-lived alpha 2 beta 2 complex and long-range radical transfer (RT). RT occurs via proton-coupled electron transfer (PCET) over a long distance (similar to 32-angstrom) and involves the formation and decay of multiple amin...