Crystal structure of the β2 adrenergic receptor-Gs protein complex

G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 ? outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.     

The industrial asymmetry of the stock price prediction with investor sentiment: Based on the comparison of predictive effects with SVR

As a representative emerging financial market, the Chinese stock market is more prone to volatility because of investor sentiment. It is reasonable to use efficient predictive methods to analyze the influence of investor sentiment on stock price forecasting. This paper conducts a comparative study about the predictive performance of artificial neural network, support vector regression (SVR) and autoregressive integrated moving average and selects SVR to study the asymmetry effect of investor sentiment on different industry index predictions. After studying the relevant financial indicators, the results divide the Shenwan first-class industries into two types and show that the industries affected by investor sentiment are composed of young companies with high growth and high operative pressure and there are a great number of investment bubbles in those companies.     

Anthropogenic influence has increased climate extreme occurrence over China

There is overwhelming evidence that anthropogenic activity has exerted a great influence on climate extremes, especially on heat events at continental to global...     

Optimal Switching Integrity Attacks on Sensors in Industrial Control Systems

In this article, an optimal switching integrity attack problem is investigated to study the response of feedback control systems under attack. The authors model the malicious attacks on sensors as additive norm bounded signals. The authors consider an attacker who is only capable of launching attacks to limited number of sensors once a time and changing the combinations of attacked sensors all over the time. The objective of this paper is to find the optimal switching sequence of these combinations and the optimal attack input. The authors solve this problem by transforming it into a traditional optimal control problem with new control variables vary continuously in the range [0, 1]. The optimal solutions of the new control variables are of bang-bang-type. Therefore, an algebraic switching condition and an optimal attack input can be obtained. Finally, numerical results are provided to illustrate the effectiveness of the methods.     

基于区间直觉模糊数ANP的体系贡献率计算方法

体系贡献率主要用于体系建设中度量装备对体系的贡献程度。为解决目前体系贡献率计算存在的一些问题,提出一种“任务–能力–指标–装备”的多层次装备指标体系结构。考虑了装备指标体系结构、网络分析法和区间直觉模糊数的特点,提出了一种基于区间直觉模糊数的网络分析法以得到更准确的体系贡献率。实验表明,该方法不仅能够解决体系贡献率计算公式现存的问题,而且与AHP(analytic hierarchy process)和ANP(analytic network process)相比,可以得到更准确的体系贡献率,为体系建设提供更有效的支持。     

一类随机非线性系统的输出反馈全局镇定

将基于增益观测器的非线性系统输出反馈全局镇定控制器设计方法推广到随机情形,使之适用于一般的随机非线性系统.与已有基于反步法设计的镇定控制器相比,该方法不要求该随机非线性系统满足严格反馈条件,对其噪声向量函数也不要求满足光滑性条件.基于李亚普诺夫第二方法,讨论了所设计的控制器稳定的条件.一个二阶仿真算例表明该控制器设计方法是有效的.     

Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma

The NLRP3 inflammasome is a critical innate immune pathway responsible for producing active interleukin (IL)-1β, which is associated with tumor development and immunity. However, the mechanisms regulating the inflammatory microenvironment, tumorigenesis and tumor immunity are unclear. Herein, we show that the NLRP3 inflammasome was over-expressed in human HNSCC tissues and that the IL-1β concentration was increased in the peripheral blood of HNSCC patients. Additionally, elevated NLRP3 inflammasome levels were detected in tumor tissues of Tgfbr1/Pten 2cKO HNSCC mice, and elevated IL-1β levels were detected in the peripheral blood serum, spleen, draining lymph nodes and tumor tissues. Blocking NLRP3 inflammasome activation using MCC950 remarkably reduced IL-1β production in an HNSCC mouse model and reduced the numbers of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Moreover, inhibiting NLRP3 inflammasome activation increased the numbers of CD4⁺ and CD8⁺ T cells in HNSCC mice. Notably, the numbers of exhausted PD-1⁺ and Tim3⁺ T cells were significantly reduced. A human HNSCC tissue microarray showed that NLRP3 inflammasome expression was correlated with the expression of CD8 and CD4, the Treg marker Foxp3, the MDSC markers CD11b and CD33, and the TAM markers CD68 and CD163, PD-1 and Tim3. Overall, our results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells. Thus, inhibition of the tumor microenvironment through the NLRP3 inflammasome/IL-1β pathway may provide a novel approach for HNSCC therapy.     

Control of a key transition from prostrate to erect growth in rice domestication

The transition from the prostrate growth of ancestral wild rice (O. rufipogon Griff.) to the erect growth of Oryza sativa cultivars was one of the most critical events in rice domestication. This evolutionary step importantly improved plant architecture and increased grain yield. Here we find that prostrate growth of wild rice from Yuanjiang County in China is controlled by a semi-dominant gene, PROG1 (PROSTRATE GROWTH 1), on chromosome 7 that encodes a single Cys(2)-His(2) zinc-finger protein. prog1 variants identified in O. sativa disrupt the prog1 function and inactivate prog1 expression, leading to erect growth, greater grain number and higher grain yield in cultivated rice. Sequence comparison shows that 182 varieties of cultivated rice, including 87 indica and 95 japonica cultivars from 17 countries, carry identical mutations in the prog1 coding region that may have become fixed during rice domestication.