-
作者：Hu, Jiashun; Rudi, Johann; Gurnis, Michael; Stadler, Georg
作者单位：Southern University of Science & Technology; Virginia Polytechnic Institute & State University; California Institute of Technology; New York University
摘要：Variable viscosity in Earth's mantle exerts a fundamental control on mantle convection and plate tectonics, yet rigorously constraining the underlying parameters has remained a challenge. Inverse methods have not been sufficiently robust to handle the severe viscosity gradients and nonlinearities (arising from dislocation creep and plastic failure) while simultaneously resolving the megathrust and bending slabs globally. Using global plate motions as constraints, we overcome these challenges b...
-
作者：Yoshida, Saishu; Kawamura, Akira; Aoki, Katsuhiko; Wiriyasermkul, Pattama; Sugimoto, Shinya; Tomiyoshi, Junnosuke; Tajima, Ayasa; Ishida, Yamato; Katoh, Yohei; Tsukada, Takehiro; Tsuneoka, Yousuke; Yamada, Kohji; Nagamori, Shushi; Nakayama, Kazuhisa; Yoshida, Kiyotsugu
作者单位：Toho University; Hiroshima University; Jikei University; Jikei University; Jikei University; Jikei University; Jikei University; Jikei University; Jikei University; Jikei University; Kyoto University; Toho University; Toho University
摘要：Hedgehog (Hh) signaling, an evolutionarily conserved pathway, plays an essential role in development and tumorigenesis, making it a promising drug target. Multiple negative regulators are known to govern Hh signaling; however, how activated Smoothened (SMO) participates in the activation of downstream GLI2 and GLI3 remains unclear. Herein, we identified the ciliary kinase DYRK2 as a positive regulator of the GLI2 and GLI3 transcription factors for Hh signaling. Transcriptome and interactome an...
-
作者：Chandrakar, Kamal Kant; Morrison, Hugh; Grabowski, Wojciech W.; Lawson, R. Paul
摘要：Rain formation is a critical factor governing the lifecycle and radiative forcing of clouds and therefore it is a key element of weather and climate. Cloud microphysics-turbulence interactions occur across a wide range of scales and are challenging to represent in atmospheric models with limited resolution. Based on past experiments and idealized numerical simulations, it has been postulated that cloud turbulence accelerates rain formation by enhancing drop collision-coalescence. We provide su...
-
作者：Lu, Fuzhi; Pausata, Francesco S. R.; Mohtadi, Mahyar
作者单位：Nanjing University; University of Quebec; University of Quebec Montreal; University of Bremen
-
作者：Xiao, Zhuo-Cheng; Lin, Kevin K.; Young, Lai-Sang
作者单位：East China Normal University; East China Normal University; University of Arizona; New York University
摘要：Biologically detailed models of brain circuitry are challenging to build and simulate due to the large number of neurons, their complex interactions, and the many unknown physiological parameters. Simplified mathematical models are more tractable, but harder to evaluate when too far removed from neuroanatomy/physiology. We propose that a multiscale model, coarse-grained (CG) while preserving local biological details, offers the best balance between biological realism and computability. This pa...
-
作者：Cocco, Simona; Posani, Lorenzo; Monasson, Remi
作者单位：Universite PSL; Ecole Normale Superieure (ENS); Sorbonne Universite; Universite Paris Cite; Sorbonne Universite; Columbia University
摘要：Predicting the effects of one or more mutations to the in vivo or in vitro properties of a wild -type protein is a major computational challenge, due to the presence of epistasis, that is, of interactions between amino acids in the sequence. We introduce a computationally efficient procedure to build minimal epistatic models to predict mutational effects by combining evolutionary (homologous sequence) and few mutational -scan data. Mutagenesis measurements guide the selection of links in a spa...
-
作者：Issigonis, Melanie; Browder, Katherine L.; Chen, Rui; Collins III, James J.; Newmark, Phillip A.
作者单位：University of Wisconsin System; University of Wisconsin Madison; The Morgridge Institute for Research, Inc.; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; University of Texas System; University of Texas Southwestern Medical Center
摘要：Germ cells are regulated by local microenvironments (niches), which secrete instructive cues. Conserved developmental signaling molecules act as niche - derived regulatory factors, yet other types of niche signals remain to be identified. Single - cell RNA - sequencing of sexual planarians revealed niche cells expressing a nonribosomal peptide synthetase ( nrps ). Inhibiting nrps led to loss of female reproductive organs and testis hyperplasia. Mass spectrometry detected the dipeptide beta- al...
-
作者：Li, Jingru; You, Chongzhao; Li, Yang; Li, Changyao; Fan, Wenjia; Chen, Zecai; Hu, Wen; Wu, Kai; Xu, H. Eric; Zhao, Li-Hua
作者单位：Nanjing University of Chinese Medicine; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Lingang Laboratory; ShanghaiTech University
摘要：Somatostatin receptor 5 (SSTR5) is an important G protein-coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high- resolution cryogenicelectron microscope structures of the SSTR5-Gi complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 & Aring; and 2.9 & Aring;, respectively. The structures reveal that binding of these peptides causes rearrangement of a hydrophobic lock, consi...
-
作者：Murali, Ranjani; Pace, Laura A.; Sanford, Robert A.; Ward, L. M.; Lynes, Mackenzie M.; Hatzenpichler, Roland; Lingappa, Usha F.; Fischer, Woodward W.; Gennis, Robert B.; Hemp, James
作者单位：University of Illinois System; University of Illinois Urbana-Champaign; California Institute of Technology; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; University of Illinois System; University of Illinois Urbana-Champaign; Smith College; California Institute of Technology; Montana State University System; Montana State University Bozeman; Montana State University System; Montana State University Bozeman; Montana State University System; Montana State University Bozeman; University of California System; University of California Berkeley
摘要：Nitrous oxide is a potent greenhouse gas whose production is catalyzed by nitric oxide reductase (NOR) members of the heme - copper oxidoreductase (HCO) enzyme superfamily. We identified several previously uncharacterized HCO families, four of which (eNOR, sNOR, gNOR, and nNOR) appear to perform NO reduction. These families have novel active - site structures and several have conserved proton channels, suggesting that they might be able to couple NO reduction to energy conservation. We isolate...
-
作者：Paige, Jonathan; Perreault, Charles
作者单位：University of Missouri System; University of Missouri Columbia; Arizona State University; Arizona State University-Tempe
摘要：Cumulative culture, the accumulation of modifications, innovations, and improvements over generations through social learning, is a key determinant of the behavioral diversity across Homo sapiens populations and their ability to adapt to varied ecological habitats. Generations of improvements, modifications, and lucky errors allow humans to use technologies and know-how well beyond what a single naive individual could invent independently within their lifetime. The human dependence on cumulati...
