分类： 药物科学 >> 结构生物学 提交时间： 2024-02-24
Heng Liu
Shimeng Guo
Antao Dai
Peiyu Xu
Xin Li
Sijie Huang
Xinheng He
Kai Wu
Xinyue Zhang
Dehua Yang
Xin Xie
H. Eric Xu
摘要： The orphan receptor GPR30, previously classified as a G protein-coupled estrogen receptor (GPER), has been a subject of debate regarding its ligand specificity. Through an integrative approach combining structure elucidation, biochemical binding, and cell signaling assays, we demonstrate that estrogen does not directly bind to or activate GPR30. Cryo-EM structures of GPR30 reveal an unexpected hydrophilic ligand-binding pocket, with striking differences from classical hydrophobic steroid-binding sites, inconsistent with estrogen binding. We further confirmed hydrophilic agonists like Lys05 as true activators of GPR30, providing structural insights into their binding mechanism and receptor activation. Our findings necessitate a paradigm shift in defining GPR30’s role in estrogen signaling, indicating that its activation occurs through mechanisms independent of estrogen binding. This study opens new avenues for developing targeted GPR30 ligands and reinterpreting its role in estrogen-mediated processes.
分类： 物理学 >> 核物理学 提交时间： 2024-02-24
摘要： The yield ratios of neutron-proton (R(n/p)) and 3H-3He (R(3H/3He)) with reduced rapidity from 0 to 0.5 were simulated for 50 MeV/u even-even 36-56Ca + 40Ca, even-even 48-78Ni + 58Ni and 100-139Sn (every third isotopes) + 112Sn at full reduced impact parameters using the isospin-dependent quantum molecular dynamics (IQMD) model. The neutron and proton density distributions and root-mean-square radii of the reaction systems were obtained using the Skyrme-Hartree-Fock model, which was used for the phase space initialization of the projectile and target in IQMD. We defined the unified neutron skin thickness as ΔRnp=2>n1/2-2>p1/2, which was negative for neutron-deficient nuclei. The unified ΔRnp values for nuclei with the same relative neutron excess from different isotopic chains were nearly equal, except for extreme neutron-rich isotopes, which is a type of scaling behavior. The yield ratios of the three isotopic chains-induced reactions, which dependent on the reduced impact parameter and the unified neutron skin thickness, were studied. The results show that both R(n/p) and R(3H/3He) decreased with a reduced impact parameter for extreme neutron-deficient isotopes; however, they increased with reduced impact parameters for extreme neutron-rich isotopes, and increased with the ΔRnpof the projectiles for all reduced impact parameters. In addition, a scaling phenomena was observed between ΔRnp and the yield ratios in peripheral collisions from different isotopic chain projectiles (except for extreme neutron-rich isotopes). Thus, R(n/p) and R(3H/3He) from peripheral collisions were suggested as experimental probes for extracting the neutron or proton skin thicknesses of non-extreme neutron-rich nuclei from different isotopic chains.
分类： 心理学 >> 教育心理学 提交时间： 2024-02-24
摘要： 精细内容反馈促进深层次的学习，如迁移。但在师生互动中反馈的呈现方式如何影响长时学习迁移及其人际神经基础尚不清楚。本研究采用面对面的师生问答反馈任务，通过两个双人实验（行为学、近红外超扫描），探究反馈的组块化呈现对学习迁移的长时促进作用、认知过程及其人际神经基础。结果发现，组块化反馈促进低知识基础学生的长时迁移。组块化错误修正在反馈呈现方式和长时迁移之间起中介作用。提供与接收组块化反馈过程中，师、生在额、顶叶出现更大的脑间同步，且额叶的脑间同步预测长时迁移与组块化错误修正。上述结果从人际视角为课堂中真实发生的教学反馈的认知神经基础提供新的理解，也为提高教学反馈效果和效率提供一些实践启示。
点击量
待评议
点击量
下载量
评论
通过
