Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

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

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Natural Products from the Genus Tephrosia

The genus Tephrosia, belonging to the Leguminosae family, is a large pantropical genus of more than 350 species, many of which have important traditional uses in agriculture. This review not only outlines the source, chemistry and biological evaluations of natural products from the genus Tephrosia worldwide that have appeared in literature from 1910 to December 2013, but also covers work related to proposed biosynthetic pathways and synthesis of some natural products from the genus Tephrosia, with 105 citations and 168 new compounds

Phycocyanin Ameliorates Colitis-Associated Colorectal Cancer by Regulating the Gut Microbiota and the IL-17 Signaling Pathway

Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota and transcriptomic analyses to investigate the effects of PC on colitis-associated cancer (CAC). Our results indicated that PC ameliorated AOM/DSS induced inflammation. PC treatment significantly reduced the number of colorectal tumors and inhibited proliferation of epithelial cell in CAC mice. Moreover, PC reduced the relative abundance of Firmicutes, Deferribacteres, Proteobacteria and Epsilonbacteraeota at phylum level. Transcriptomic analysis showed that the expression of genes involved in the intestinal barrier were altered upon PC administration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the IL-17 signaling pathway was affected by PC treatment. The study demonstrated the protective therapeutic action of PC on CAC

Proteomic Identification of Plasma Components in <i>Tachypleus tridentatus</i> and Their Effects on the Longitudinal Bone Growth Rate in Rats

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10–30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10–30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10–30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent

A new diketopiperazine from South China Sea marine sponge <i>Callyspongia</i> sp.

<div><p>Further chemical investigation on the marine sponge <i>Callyspongia</i> sp. collected from South China Sea led to the isolation of a new diketopiperazine, named callysponine A (<b>1</b>), as well as four known diketopiperazines, namely cyclo-(Gly-Pro) (<b>2</b>), cyclo-(Thr-Pro) (<b>3</b>), cyclo-(Ile-Pro) (<b>4</b>) and cyclo-(Pro-Pro) (<b>5</b>). The new structure was determined on the basis of NMR and MS analysis, and the absolute stereochemistry was defined by analysis of the coupling constants and optical rotation. The structures of the known compounds were identified by comparing their spectroscopic data with those reported in the literature. Compounds <b>1</b>–<b>5</b> did not inhibit the growth of HepG2 (hepatoma carcinoma cell), A549 (lung carcinoma cell) and HeLa (cervical cancer cell) cell lines.</p></div

Assimilating FY-4A Lightning and Radar Data for Improving Short-Term Forecasts of a High-Impact Convective Event with a Dual-Resolution Hybrid 3DEnVAR Method

A dual-resolution, hybrid, three-dimensional ensemble-variational (3DEnVAR) data assimilation method combining static and ensemble background error covariances is used to assimilate radar data, and pseudo-water vapor observations to improve short-term severe weather forecasts with the Weather Research and Forecast (WRF) model. The higher-resolution deterministic forecast and the lower-resolution ensemble members have 3 and 9 km horizontal resolution, respectively. The water vapor pseudo-observations are derived from the combined use of total lightning data and cloud top height from the Fengyun-4A(FY-4A) geostationary satellite. First, a set of single-analysis experiments are conducted to provide a preliminary performance evaluation of the effectiveness of the hybrid method for assimilating multisource observations; second, a set of cycling analysis experiments are used to evaluate the forecast performance in convective-scale high-frequency analysis; finally, different hybrid coefficients are tested in both the single and cycling experiments. The single-analysis results show that the combined assimilation of radar data and water vapor pseudo-observations derived from the lightning data is able to generate reasonable vertical velocity, water vapor and hydrometeor adjustments, which help to trigger convection earlier in the forecast/analysis and reduce the spin-up time. The dual-resolution hybrid 3DEnVAR method is able to adjust the wind fields and hydrometeor variables with the assimilation of lightning data, which helps maintain the triggered convection longer and partially suppress spurious cells in the forecast compared with the three-dimensional variational (3DVAR) method. A cycling analysis that introduced a large number of observations with more frequent small adjustments is able to better resolve the observed convective events than a single-analysis approach. Different hybrid coefficients can affect the forecast results, either in the single deterministic or cycling analysis experiments. Overall, we found that a static coefficient of 0.4 and an ensemble coefficient of 0.6 yields the best forecast skill for this event

Brominated Depsidones with Antibacterial Effects from a Deep-Sea-Derived Fungus <i>Spiromastix</i> sp.

Eleven new brominated depsidones, namely spiromastixones U-Z5 (1–11) along with five known analogues (12–16), were isolated from a deep-sea-derived fungus Spiromastix sp. through the addition of sodium bromide during fermentation. Their structures were elucidated by extensive analysis of the spectroscopic data including high-resolution MS and 1D and 2D NMR data. Compounds 6–10 and 16 exhibited significant inhibition against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) with MIC values ranging from 0.5 to 2.0 μM. Particularly, tribrominated 7 displayed the strongest activity against MRSA and VRE with a MIC of 0.5 and 1.0 μM, respectively, suggesting its potential for further development as a new antibacterial agent