Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1.

BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins.DOI: http://dx.doi.org/10.7554/eLife.02362.001

Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification.

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines

Structural analysis of site-directed mutants of cellular retinoic acid-binding protein II addresses the relationship between structural integrity and ligand binding

A water network stabilizes the structure of cellular retionic acid binding protein II

Pressure-induced electronic topological transition and superconductivity in topological insulator Bi2Te2.1Se0.9

Great attention has been drawn to topological superconductivity due to its potential application in topological quantum computing. Meanwhile, pressure is regarded as a powerful tool for tuning electronic structure and even inducing superconductivity in topological insulators. As a well-defined topological insulator, Bi2Te2.1Se0.9 can be a suitable candidate to search for topological superconductivity and study its intrinsic property. In this paper, we report the occurrence of superconductivity and electronic topological transition (ETT) in Bi2Te2.1Se0.9 with applied pressure. Superconductivity can be observed at 2.4 GPa with the Tconset around 6.6 K in Bi2Te2.1Se0.9 by resistance measurement, and the corresponding structure resolved by X-ray diffraction and Raman experiments doesn't change below the pressure of 8.4 GPa. Moreover, at about 3.0 GPa, the abnormal changes of c/a as well as the full width at half maximum (FWHM) of mode indicate the occurrence of electronic topological transition (ETT). These results indicate that superconductivity can be realized in doped topological insulator Bi2Te2.1Se0.9 in the low-pressure rhombohedral phase

Network pharma cology and GEO chip based elucidation of mechanisms underlying the use of Yi Tieqing for prevention and treatment of postoperative nausea and vomiting

Purpose: To investigate the mechanism(s) involved in the use of Yi Tieqing for the prevention and treatment of postoperative nausea and vomiting (PONV), using network pharmacology and GEO chip. Methods: The chemical constituents and functional targets of five traditional Chinese medicines in Yi Tieqing were obtained by searching TCMSP database. The PONV disease targets were identified through DisGeNET, GeneCards and DrugBank databases, and differential expression genes of the GEO database chip (GSE7762) were mined. From the intersections of the component targets and disease targets, the core targets of drugs and diseases were obtained. The core targets were investigated in R language using GO-biological process and KEGG enrichment analyses, and their biological activities were verified via molecular docking. Finally, the severity and incidence of PONV in control and treatment groups were determined and compared. Results: A total of 254 bioactive components and 301 related potential targets were obtained from the TCMSP database. There were 2092 related targets in PONV, and 6 intersecting targets were obtained from Venn diagram. The results of GO biological process and KEGG enrichment analysis showed that the incidence of PONV was strongly correlated with the negative regulation of response to wounding and nervous system. Clinical results showed that from 24 – 48 h (T2) after operation, the severity and incidence of PONV in the treatment group were significantly lower than those in the control group (p < 0.05). Conclusion: Yi Tieqing alleviates PONV through multi-components, multi-targets, and multi-pathways

Non-Abelian Collective Excitations in Unlinearized Quark-Gluon Plasma Media

We study the effect of unlinearized medium on the collective excitations in quark-gluon plasma. We present two kinds of non-Abelian oscillation solutions which respectively correspond to weakly and strongly nonlinear coupling of field components in color space. We also show that the weakly nonlinear solution is similar to Abelian-like one but has the frequency shift, which is of order $g^2T$, from eigenfrequency.Comment: 7 page

A Four-Step Method for Optimising the Normal Water Level of Reservoirs Based on a Mathematical Programming Model—A Case Study for the Songyuan Backwater Dam in Jilin Province, China

Determination of the optimal normal water level of reservoirs (RNWL) was investigated, incorporating environmental ecology as a primary consideration. RNWL constitutes a relatively significant eigenvalue of any water conservancy project. In the present study, a four-step method based on a mathematical programming model and suitable for RNWL decision making was developed and applied to the water conservancy project of the Songyuan backwater dam in China. System analysis, correlation analysis, significance testing, principal component analysis, sensitivity analysis, and system optimisation theory are used in the solution process. In this study, various factors that impact the economic viability, engineering characteristics, environmental and urban ecology are considered for holistic optimisation. The study shows that the proposed four-step method may provide a feasible quantitative form of support for RNWL decision making

Pore Characteristics of the Upper Carboniferous Taiyuan Shale in Liaohe Depression

High pressure mercury, nitrogen adsorption, nano-CT, and scanning electron microscope with energy spectrum analysis were conducted on core shale samples for studying the characteristics of Taiyuan formation in the eastern uplift of Liaohe depression. The research results show that the shale gas reservoir pores are mainly open pores such as the wedge-shape pores and parallel-plate pores. By a genetic type, pores mainly include organic pore, pyrite crystal particle pore, illite intragranular pore, illite-smectite mixed layer intragranular pore, and feldspar dissolved pore. The micropore and mesopore play an important role in shale gas reservoir, and their surface area and pore volume are 9.56 m2/g, 0.0414 mL/g, 97.3%, and 68.8% respectively. The pores diameter presents a bimodal distribution with two main peaks at 43 nm and 6.35 μm. Based on the nano-CT, the porosity is 4.36% and the permeability is 204 nD. The brittle minerals played a supportive and protective role for the pores and controlled their spatial distribution