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202 result(s) for "Qian, Wenyu"
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Cryo-EM structure of the β-1,3-glucan synthase FKS1-Rho1 complex
β-1,3 Glucan synthase (GS) is essential for fungal cell wall biosynthesis. The GS holoenzyme comprises the glycosyltransferase FKS1 and its regulatory factor Rho1, a small GTPase. However, the mechanism by which Rho1 activates FKS1 in a GTP-dependent manner remains unclear. Here, we present two cryo-EM structures of FKS1, apo and in complex with Rho1. FKS1 adopts a cellulose synthase-like conformation. The interaction between Rho1 and FKS1 is enhanced in the presence of GTPγS. Rho1 is positioned within a pocket between the glycosyltransferase domain of FKS1 (GT domain) and the transmembrane helix spanning TM7-15. Comparison of the two structures reveals extensive conformational changes within FKS1. These alterations suggest that Rho1’s GTP/GDP cycling may act as a molecular pump, promoting a dynamic transition between the resting and active states of FKS1. Notably, Rho1 triggers FKS1 conformational changes that may push the growing glucan chain into FKS1’s transmembrane channel, thereby facilitating β-1,3-glucan elongation. Cryo-EM structures of apo-FKS1 and the FKS1-Rho1 complex reveal how Rho1 activates FKS1, driving conformational changes of FKS1 in β−1,3- glucan synthesis.
Structural-guided identification of two modulators of β−1,3-glucan synthase FKS1
FKS1 is a β−1,3-glucan synthase critical for fungal cell wall formation and a target for antifungal drugs such as echinocandin and ibrexafungerp. However, the mechanisms regulating FKS1 activity remain largely unknown. Here, we reveal that transfer RNA (tRNA) acts as an endogenous inhibitor, whereas GSR1 functions as a stabilizer of FKS1. The cryo-EM structure of FKS1 adopts a tRNA-mediated homodimer configuration, representing a quiescent state of β−1,3-glucan synthase. Unexpectedly, the copurified endogenous tRNA is identified as a potent inhibitor that suppresses FKS1 activity. Moreover, high-resolution cryo-EM density analysis enable the identification of GSR1 as an additional binding partner of FKS1. Mutagenesis experiments confirm the interaction between FKS1 and GSR1. Evolutionarily conserved GSR1 is found to increase the stability of FKS1 in β−1,3-glucan biosynthesis. Collectively, our findings identify both tRNA and GSR1 as intrinsic modulators of β−1,3-glucan biosynthesis, thereby providing opportunities for the further development of FKS1-targeted antifungal drugs. This study discovers that tRNA directly binds and regulates the membrane protein FKS1, a β-1,3-glucan synthase essential for fungal cell wall formation. Cryo-EM and biochemical analyses show how tRNA and GSR1 control FKS1 activity and fungal growth.
Aryl Azocarboxylate Compounds - Syntheses from Quinone Derivatives and Aryl Radical Generation
Aryl azocarboxylate compounds remain underutilized as synthetic building blocks, despite the tremendous development of their reactivity. One of the contributing factors to this phenomenon is the limited synthetic method to access this class of compounds, constraining the scope of available aryl azocarboxylates. The prevailing method to synthesize aryl azocarboxylate involves diazotization of anilines, reduction to aryl hydrazines, followed by nucleophilic substitution to aryl hydrazides and oxidation to aryl azocarboxylates. To address this challenge, we developed a novel strategy to access aryl azocarboxylate motifs from a condensation process between quinone derivatives and carbazates. We also demonstrated quinone derivatives can be used to construct substituted aromatic rings, by further functionalization of para-quinones after condensation, installing two orthogonal functional handles. We further recognized the potentials of aryl azocarboxylates in aryl radical chemistry, and we developed both TMSOTf-2,6-lutidine condition and Cu(II)-mediated aryl radical generation strategies.
Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Monlb
Numb is an endocytic protein that plays crucial roles in diverse cellular processes such as asymmetric cell division, cell migration and differentiation. However, the molecular mechanism by which Numb regulates endocytic trafficking is poorly understood. Here, we demonstrate that Numb is a docking regulator for homotypic fusion of early endo- somes (EEs). Numb depletion causes clustered but unfused EEs, which can be rescued by overexpressing cytosolic Numb 65 and Numb 71 but not plasma membrane-attached Numb 66 or Numb 72. Time-lapse analysis reveals that paired vesicles tend to tether but not fuse with each other in the absence of Numb. We further show that Numb binds to another docking regulator, Monlb, and is required for the recruitment of cytosolic Monlb to the EE membrane. Consistent with this, deletion of Monlb causes similar defects in EE fusion. Our study thus identifies a novel mecha- nism by which Numb regulates endocytic sorting by mediating EE fusion.
Numb regulates vesicular docking for homotypic fusion of early endosomes via membrane recruitment of Mon1b
Numb is an endocytic protein that plays crucial roles in diverse cellular processes such as asymmetric cell division, cell migration and differentiation. However, the molecular mechanism by which Numb regulates endocytic trafficking is poorly understood. Here, we demonstrate that Numb is a docking regulator for homotypic fusion of early endosomes (EEs). Numb depletion causes clustered but unfused EEs, which can be rescued by overexpressing cytosolic Numb 65 and Numb 71 but not plasma membrane-attached Numb 66 or Numb 72. Time-lapse analysis reveals that paired vesicles tend to tether but not fuse with each other in the absence of Numb. We further show that Numb binds to another docking regulator, Mon1b, and is required for the recruitment of cytosolic Mon1b to the EE membrane. Consistent with this, deletion of Mon1b causes similar defects in EE fusion. Our study thus identifies a novel mechanism by which Numb regulates endocytic sorting by mediating EE fusion.
Nanhuaphasma Chen, He & Li, 2002 is a junior synonym of Dajaca Brunner von Wattenwyl, 1893 (Phasmatodea, Aschiphasmatidae, Dajacini)
The genus Nanhuaphasma Chen, He & Li, 2002 was established as a member of the family Pseudophasmatidae Rehn, 1904 (now belonging to Aschiphasmatidae Brunner von Wattenwyl, 1893) based on the male of N. hamicercum Chen & He, 2002. We review the status of Nanhuaphasma and N. hamicercum by examining the holotype and male and female non-types which were collected in same location as the holotype. We find that Nanhuaphasma is a junior synonym of Dajaca Brunner von Wattenwyl, 1893 and N. hamicercum is a junior synonym of D. napolovi Brock, 2000. Complementing egg morphology of D. napolovi and keys to eight species of Dajaca are provided.
The Influence of ESG Performance on Corporate Value: An Empirical Analysis of Chinese A-Share Listed Sports Companies
This study uses a two-way fixed-effect model to analyze the impact of ESG performance on corporate value based on the quarterly data of Chinese A-share listed sports companies from 2018 to 2022. The results prove that (1) The ESG performance of sports enterprises positively affects corporate value: the higher the ESG score is, the higher the corporate value is. (2) Mechanism analysis shows that financing constraints play a partially mediating role in the relationship between ESG performance and corporate value. (3) Heterogeneity analysis shows that corporate political relations will weaken the facilitating effect of ESG performance on corporate value. The stronger the political relations are, the weaker the facilitating effect of ESG performance on corporate value. Compared with that during the bear market, the performance of ESG in the bull market has a greater facilitating effect on corporate value. Compared with sports service enterprises, sports goods enterprises’ ESG performance has a stronger facilitating effect on corporate value. Plain Language Summary Research question: This paper provide an in-depth discussion of the impact of sports enterprises’ ESG (environment, social responsibility and corporate governance) performance on corporate value. Research methods: This study uses a two-way fixed-effect model to analyze the impact of ESG performance on corporate value based on the quarterly data of Chinese A-share listed sports companies from 2018 to 2022. Results and findings: The results prove that (1) The ESG performance of sports enterprises positively affects corporate value: the higher the ESG score is, the higher the corporate value is. (2) Mechanism analysis shows that financing constraints play a partially mediating role in the relationship between ESG performance and corporate value. (3) Heterogeneity analysis shows that corporate political relations will weaken the facilitating effect of ESG performance on corporate value. The stronger the political relations are, the weaker the facilitating effect of ESG performance on corporate value. Compared with that during the bear market, the performance of ESG in the bull market has a greater facilitating effect on corporate value. Compared with sports service enterprises, sports goods enterprises’ ESG performance has a stronger facilitating effect on corporate value. Implications: It is helpful for relevant enterprises to clarify the positive influence of ESG performance on corporate value to stimulate the internal motivation of sports enterprises to fulfil their ESG responsibilities while boosting the sustainable development of sports enterprises and the green and coordinated development of the sports industry. Limitations: The overall data is relatively less, and the research methods need to be enriched.
Decoding the development of the human hippocampus
The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and the consolidation of information from short-term memory to long-term memory 1 , 2 . Here we use single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC–seq) analysis to illustrate the cell types, cell linage, molecular features and transcriptional regulation of the developing human hippocampus. Using the transcriptomes of 30,416 cells from the human hippocampus at gestational weeks 16–27, we identify 47 cell subtypes and their developmental trajectories. We also identify the migrating paths and cell lineages of PAX6 + and HOPX + hippocampal progenitors, and regional markers of CA1, CA3 and dentate gyrus neurons. Multiomic data have uncovered transcriptional regulatory networks of the dentate gyrus marker PROX1. We also illustrate spatially specific gene expression in the developing human prefrontal cortex and hippocampus. The molecular features of the human hippocampus at gestational weeks 16–20 are similar to those of the mouse at postnatal days 0–5 and reveal gene expression differences between the two species. Transient expression of the primate-specific gene NBPF1 leads to a marked increase in PROX1 + cells in the mouse hippocampus. These data provides a blueprint for understanding human hippocampal development and a tool for investigating related diseases. Single-cell RNA sequencing is used to catalogue and explore the developmental trajectories of more than 30,000 cells in the developing human hippocampus.
MapTRv2: An End-to-End Framework for Online Vectorized HD Map Construction
High-definition (HD) map provides abundant and precise static environmental information of the driving scene, serving as a fundamental and indispensable component for planning in autonomous driving system. In this paper, we present Map TR ansformer, an end-to-end framework for online vectorized HD map construction. We propose a unified permutation-equivalent modeling approach, i . e ., modeling map element as a point set with a group of equivalent permutations, which accurately describes the shape of map element and stabilizes the learning process. We design a hierarchical query embedding scheme to flexibly encode structured map information and perform hierarchical bipartite matching for map element learning. To speed up convergence, we further introduce auxiliary one-to-many matching and dense supervision. The proposed method well copes with various map elements with arbitrary shapes. It runs at real-time inference speed and achieves state-of-the-art performance on both nuScenes and Argoverse2 datasets. Abundant qualitative results show stable and robust map construction quality in complex and various driving scenes. Code and more demos are available at https://github.com/hustvl/MapTR for facilitating further studies and applications.
Quantum entanglement between partons in a strongly coupled quantum field theory
A bstract We perform a first-principles, non-perturbative investigation of quantum entanglement between partonic constituents in a strongly coupled 3+1-dimensional scalar Yukawa theory, using light-front Hamiltonian methods with controlled Fock-space truncations. By explicitly constructing reduced density matrices for (mock) nucleon, pion, and anti-nucleon subsystems from light-front wave functions, we compute key entanglement witnesses, including von Neumann entropy, mutual information, and linear entropy, in both quenched (no sea pairs) and unquenched frameworks. We find that the entanglement entropy is closely related to the Shannon entropy of the transverse momentum dependent distribution, establishing a link between quantum information and parton structure. In contrast, the unquenched theory reveals genuinely non-classical correlations: the entanglement entropy cannot be reduced to any Shannon entropy of normalized parton distributions, demonstrating that the full hadronic wave function encodes quantum information beyond classical probabilities. Our findings highlight the role of entanglement as a fundamental probe of non-perturbative dynamics in relativistic quantum field theory and lay the groundwork for extending these concepts to QCD and future collider phenomenology.