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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.

Clinical application of inhaled glucocorticoids (GCs) has been hampered in the case of steroid-resistant severe asthma. To overcome this limitation, we have developed a series of highly potent GCs, including VSGC12, VSG158, and VSG159 based on the structural insight into the glucocorticoid receptor (GR). Particularly, VSG158 exhibits a maximal repression of lung inflammation and is 10 times more potent than the currently most potent clinical GC, Fluticasone Furoate (FF), in a murine model of asthma. More importantly, VSG158 displays a unique property to reduce neutrophilic inflammation in a steroid-resistant airway inflammation model, which is refractory to clinically available GCs, including dexamethasone and FF. VSG158 and VSG159 are able to deliver effective treatments with reduced off-target and side effects. In addition, these GCs also display pharmacokinetic properties that are suitable for the inhalation delivery method for asthma treatment. Taken together, the excellent therapeutic and side-effect profile of these highly potent GCs holds promise for treating steroid-resistant severe asthma.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.

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]

Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCF.sup.D3 ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCF.sup.D3 ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex. Strigolactones (SLs), key regulators of plant growth, are believed to mediate their responses through a proposed receptor (D14) that interacts with an F-box protein (D3) to form a D14-SCF.sup.D3 protein complex; here the perception of SLs by the D14-SCF.sup.D3 complex and the control of gene expression are linked by the finding that DWARF 53, a repressor protein of SL signalling, interacts with the D14-SCF.sup.D3 complex and is ubiquitinated and degraded in a SL-dependent manner. Strigolactone receptor identified The strigolactones are key regulators of plant growth, controlling the formation of secondary shoots and regulating root branching. Strigolactone responses are mediated through a proposed receptor (D14) that interacts with an F-box protein (D3). Now, in two related publications, Liang Jiang et al. and Feng Zhou et al. demonstrate a functional link between the perception of strigolactones by D14/D3 and the control of gene expression in rice. They show that the protein DWARF53 (D53), of previously unknown function, acts as a repressor of strigolactone signalling and that strigolactones induce its degradation. D53 interacts with the D14-D3 complex and is ubiquitinated and degraded by the proteasome in a strigolactone-dependent manner., Author(s): Liang Jiang [sup.1] , Xue Liu [sup.1] , Guosheng Xiong [sup.1] , Huihui Liu [sup.1] , Fulu Chen [sup.1] , Lei Wang [sup.1] , Xiangbing Meng [sup.1] , Guifu [...]

Abstract Background Steroid receptors play major roles in the development, differentiation, and homeostasis of normal and malignant tissue. STAMP is a novel coregulator that not only enhances the ability of p160 coactivator family members TIF2 and SRC-1 to increase gene induction by many of the classical steroid receptors but also modulates the potency (or EC50) of agonists and the partial agonist activity of antisteroids. These modulatory activities of STAMP are not limited to gene induction but are also observed for receptor-mediated gene repression. However, a physiological role for STAMP remains unclear. Methods The growth rate of HEK293 cells stably transfected with STAMP plasmid and overexpressing STAMP protein is found to be decreased. We therefore asked whether different STAMP levels might also contribute to the abnormal growth rates of cancer cells. Panels of different stage human cancers were screened for altered levels of STAMP mRNA. Those cancers with the greatest apparent changes in STAMP mRNA were pursued in cultured cancer cell lines. Results Higher levels of STAMP are shown to have the physiologically relevant function of reducing the growth of HEK293 cells but, unexpectedly, in a steroid-independent manner. STAMP expression was examined in eight human cancer panels. More extensive studies of ovarian cancers suggested the presence of higher levels of STAMP mRNA. Lowering STAMP mRNA levels with siRNAs alters the proliferation of several ovarian cancer tissue culture lines in a cell line-specific manner. This cell line-specific effect of STAMP is not unique and is also seen for the conventional effects of STAMP on glucocorticoid receptor-regulated gene transactivation. Conclusions This study indicates that a physiological function of STAMP in several settings is to modify cell growth rates in a manner that can be independent of steroid hormones. Studies with eleven tissue culture cell lines of ovarian cancer revealed a cell line-dependent effect of reduced STAMP mRNA on cell growth rates. This cell-line dependency is also seen for STAMP effects on glucocorticoid receptor-mediated transactivation. These preliminary findings suggest that further studies of STAMP in ovarian cancer may yield insight into ovarian cancer proliferation and may be useful in the development of biomarker panels.

The structure/ activity relationships of the protein, glucocorticoid modulatory element binder (GMEB)-2 are documented and the results are compared with GMEB-1. Mechanism of action of GMEB-2 supports the conclusion that the ability of factors to modulate the position of the dose-response curve of glucocorticoid receptors (GRs) complex is unrelated to the effect on the total levels of GR-induced gene expression.