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[ Objective ] The aim of this study is to study the effects of short-term warming and precipitation reduction on the species diversity , functional traits , and productivity , and to reveal the response of com- munity characteristics to climate change in sandy grassland. [ Methods ] The authors investigated the com- bined effects of precipitation reduction ( 0% , 20% , 40% and 60% ) and warming on plant community com- position , species diversity , and functional trait , as well as relationship between community characteristics and environmental factors using open-top chambers ( OTCs ) to investigate the characteristics in semi-aird sands grassland of Horqin. [ Results ] ( 1 ) Short-term warming and precipitation reduction led to changes in the plant community composition , community coverage , and aboveground biomass were significantly re- duced and species dominance of sandy grassland , suchas dominant species of Artemisia scoparia , Lespede- za davurica . ( 2 ) Short-term warming reduced Margalef richness index , Simpson index , Shannon index , and Pielou index , but short-term precipitation reduction had no effect on species diversities. ( 3 ) Short- term warming increased the height and leaf dry matter content , and reduced leaf thickness , while short- term precipitation reduction increased leaf dry matter content and leaf thickness , and reduced the height , leaf area ratio of plant community. ( 4 ) Short-term warming was the main environmental factor affecting the species diversity and functional traits in sandy grassland. [ Conclusion ] Short-term warming and precipitation reduction change community characteristics , but the temperature is the main environmental factor affect- ing community characteristics in sandy grassland.

The histamine H4 receptor (H4R) plays key role in immune cell function and is a highly valued target for treating allergic and inflammatory diseases. However, structural information of H4R remains elusive. Here, we report four cryo-EM structures of H4R/Gi complexes, with either histamine or synthetic agonists clobenpropit, VUF6884 and clozapine bound. Combined with mutagenesis, ligand binding and functional assays, the structural data reveal a distinct ligand binding mode where D943.32 and a π-π network determine the orientation of the positively charged group of ligands, while E1825.46, located at the opposite end of the ligand binding pocket, plays a key role in regulating receptor activity. The structural insight into H4R ligand binding allows us to identify mutants at E1825.46 for which the agonist clobenpropit acts as an inverse agonist and to correctly predict inverse agonism of a closely related analog with nanomolar potency. Together with the findings regarding receptor activation and Gi engagement, we establish a framework for understanding H4R signaling and provide a rational basis for designing novel antihistamines targeting H4R.The histamine H4 receptor (H4R) plays key roles in immune cell function. Here, the authors report structures of H4R-Gi complex with various ligands bound, revealing distinct ligand binding modes and a basis for rational design of novel antihistamines targeting H4R. [ABSTRACT FROM AUTHOR]

Biodiversity is sensitive to climate change and human activity. Grazing management practices have a profound impact on plant species–genetic diversity in grassland and woodland communities. In this study, we explored the responses of species and genetic diversity to grazing in Ulmus pumila L. communities in the Hunshandak Sandy Land, analyzed the relationship between species and genetic diversity, and revealed the effects of climate factors on them. We found that the dominant species were Spiraea trilobata, Caragana microphylla and Artemisia intramongolica in U. pumila communities. Plant species richness in the banned grazing (BG) and seasonal grazing (SG) communities was significantly higher than that in the delayed grazing (DG) community. Plant Simpson's diversity index showed a downward trend with increasing grazing duration. There was no difference in allelic richness in nuclear DNA (nrDNA) of U (U. pumila) and chloroplast DNA (cpDNA) of NU (other dominant species besides U. pumila) among grazing management types. The expected heterozygosity of U in nrDNA and cpDNA was significantly affected by grazing management, and the trend was BG > SG > DG. The genetic diversity of U was lower than that of NU. The genetic diversity characteristics of U in cpDNA were lower than those in nrDNA. The analysis of molecular variance (AMOVA) showed that 98.08% of the variation in U and 95.25% of the variation in NU was attributed within populations and the differences within grazing management types were 13.35% in U and 24.08% in NU (p < 0.001). The species richness of communities was positively correlated with the genetic diversity of U, NU and all dominant species (U + NU) in communities. The nineteen climatic variables together explained 94.24% and 79.08% of the total variation in U and NU genetic and species diversity. The mean temperature of the warmest quarter and temperature seasonality were the main factors affecting genetic diversity (p = 0.046; 0.01), while the maximum temperature of the warmest month was the main factor affecting species diversity (p = 0.05). [ABSTRACT FROM AUTHOR]

WNT signaling is fundamental in development and homeostasis, but how the Frizzled receptors (FZDs) propagate signaling remains enigmatic. Here, we present the cryo-EM structure of FZD4 engaged with the DEP domain of Dishevelled 2 (DVL2), a key WNT transducer. We uncover a distinct binding mode where the DEP finger-loop inserts into the FZD4 cavity to form a hydrophobic interface. FZD4 intracellular loop 2 (ICL2) additionally anchors the complex through polar contacts. Mutagenesis validates the structural observations. The DEP interface is highly conserved in FZDs, indicating a universal mechanism by which FZDs engage with DVLs. We further reveal that DEP mimics G-protein/β-arrestin/GRK to recognize an active conformation of receptor, expanding current GPCR engagement models. Finally, we identify a distinct FZD4 dimerization interface. Our findings delineate the molecular determinants governing FZD/DVL assembly and propagation of WNT signaling, providing long-sought answers underlying WNT signal transduction., (© 2024. The Author(s).)

The lysophosphatidylserine (LysoPS) receptor P2Y10, also known as LPS 2 , plays crucial roles in the regulation of immune responses and holds promise for the treatment of autoimmune diseases. Here, we report the cryoelectron microscopy (cryo-EM) structure of LysoPS-bound P2Y10 in complex with an engineered G 13 heterotrimeric protein. The structure and a mutagenesis study highlight the predominant role of a comprehensive polar network in facilitating the binding and activation of the receptor by LysoPS. This interaction pattern is preserved in GPR174, but not in GPR34. Moreover, our structural study unveils the essential interactions that underlie the Gα 13 engagement of P2Y10 and identifies key determinants for Gα 12 -vs.-Gα 13 -coupling selectivity, whose mutations selectively disrupt Gα 12 engagement while preserving the intact coupling of Gα 13 . The combined structural and functional studies provide insights into the molecular mechanisms of LysoPS recognition and Gα 12/ 13 coupling specificity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The histamine H 4 receptor (H 4 R) plays key role in immune cell function and is a highly valued target for treating allergic and inflammatory diseases. However, structural information of H 4 R remains elusive. Here, we report four cryo-EM structures of H 4 R/G i complexes, with either histamine or synthetic agonists clobenpropit, VUF6884 and clozapine bound. Combined with mutagenesis, ligand binding and functional assays, the structural data reveal a distinct ligand binding mode where D94 3.32 and a π-π network determine the orientation of the positively charged group of ligands, while E182 5.46 , located at the opposite end of the ligand binding pocket, plays a key role in regulating receptor activity. The structural insight into H 4 R ligand binding allows us to identify mutants at E182 5.46 for which the agonist clobenpropit acts as an inverse agonist and to correctly predict inverse agonism of a closely related analog with nanomolar potency. Together with the findings regarding receptor activation and G i engagement, we establish a framework for understanding H 4 R signaling and provide a rational basis for designing novel antihistamines targeting H 4 R., (© 2024. The Author(s).)

Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies. A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding pocket of receptors; however, the detailed mechanism remains obscure. Here, we present cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with G q , G s , G i , and G 12 . The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms of aGPCR activation. The structures also reveal the uncharted structural information of GPCR/G 12 coupling. A comparison of G q , G s , G i , and G 12 engagements with ADGRL3 reveals the key determinant of G-protein coupling on the far end of αH5 of Gα. A detailed analysis of the engagements allows us to design mutations that specifically enhance one pathway over others. Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling selectivity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)