Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.

     

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.     

改进的多方向融合图像插值算法

为了解决数字图像插值过程中出现的边缘模糊和锯齿现象,提出一种改进的多方向融合图像插值算法.该算法将图像分为平坦区域和边缘区域,平坦区域采用双线性插值算法进行插值,边缘区域采用多方向融合算法进行插值.实验结果表明,该算法运算复杂度小,其结果在主观视觉效果和客观指标方面都有很大的改善,且适用于任意倍数的插值放大.     

A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation

Autosomal dominant polycystic liver disease results from mutations in PRKCSH or SEC63. The respective gene products, glucosidase IIβ and SEC63p, function in protein translocation and quality control pathways in the endoplasmic reticulum. Here we show that glucosidase IIβ and Sec63p are required in mice for adequate expression of a functional complex of the polycystic kidney disease gene products, polycystin-1 and polycystin-2. We find that polycystin-1 is the rate-limiting component of this complex and that there is a dose-response relationship between cystic dilation and levels of functional polycystin-1 following mutation of Prkcsh or Sec63. Reduced expression of polycystin-1 also serves to sensitize the kidney to cyst formation resulting from mutations in Pkhd1, the recessive polycystic kidney disease gene. Finally, we show that proteasome inhibition increases steady-state levels of polycystin-1 in cells lacking glucosidase IIβ and that treatment with a proteasome inhibitor reduces cystic disease in orthologous gene models of human autosomal dominant polycystic liver disease.     

COVERING TWO DIGRAPHS WITH ARBORESCENCES

Let G_1 and G_2 be finite digraphs,both with vertex set V.Suppose that each vertexv of V has nonnegative integers f(v) and g(v) with f(v)≤g(v),and each arc e of G_4 hasnonnegative integers a_i(e) and b_i(e) with a_i(e)≤b_i(e),i=1,2.In this paper we give anecessary and sufficient condition for the existence of k arborescences in G_4 covering each are(?) of G_i at least a_i(e) and at most b_i(e) times,i=1,2,and satisfying the condition that foreach v in Vf(v)≤r_1(v)=r_2(v)≤g(v)where r_4(v) denote the number of the arborescences in G_(?) rooted at v.     

基于区域叠合有限元技术预测三维编织复合材料弹性性能

本文基于区域叠合有限元技术预测三维四向编织复合材料弹性性能。在该方法中,分别建立相互独立的纤维增强相有限元模型和复合材料整体区域(包括所有增强相和基体相所占几何空间)有限元模型,两相模型在空间叠合组成复合材料模型,运用节点自由度耦合技术使两相模型满足变形协调关系,通过对两相模型赋予适当的材料属性以使所建复合材料模型具有与实际复合材料等效的力学特性。该方法较传统方法显著缩短了建模时间,降低了建模难度。区域叠合法的数值模拟结果与传统方法预测结果一致。本文的研究为进一步研究编织复合材料非线性宏观力学特性和渐进损伤过程模拟奠定基础。     

UNIX操作系统初始化过程分析

本文作者曾对UNIX分时操作系统第六版和第七版的核心代码作过分析,尔后又对该系统的几个重要的外围程序和工具性程序做了解剖。UNIX初始化程序(包括init,getty和login)规模小、结构简单;但是,对初始化过程的深入了解,有助于理解系统活动的全过程,同时也是分析其他程序(如Shell)所不可缺少的准备。     

分散H∞低阶控制器在不确定电力系统中的应用

提出了一种新的方法为具有不确定性的实际电力系统设计分散鲁棒H∞阻尼控制器。采用多胞型模型将系统运行状态的各种变化描述为以若干个典型运行参数为顶点的凸集。分散H∞控制器的设计可以归结为基于同伦参数法的两个线性矩阵不等式的求解问题。所提的方法可以得出较低阶的鲁棒控制器，具有工程实用性。将其与系统模型降阶法相结合，可进一步减轻计算负担，进而适用于实际电力系统的控制器求解。算法分别用于SVC的分散附加阻尼控制器和19机IEEE标准测试系统的PSS设计。算例结果表明，分散控制器相互协调，不但显著地提升系统的阻尼比，使其具有良好的抗干扰能力，且对于严重故障后产生的持续振荡具有很好的抑制作用。     

国内外旅游景区人力资源开发与管理模式研究——以美国迪斯尼乐园和中国深圳世界之窗、华侨城为例

本文简要介绍了美国迪斯尼乐园和中国深圳世界之窗、华侨城的人力资源开发与管理模式,分析了它们取得成功的经验,力求为促进国内其他旅游景区的人力资源开发与管理提供一点可供参考的思路.     

液动冲击器测试系统的研究

分析和比较了测试破岩冲击器冲击能量的各种方法，根据冲击力法的测试原理和特点，选用冲击力法测试破岩冲击器的性能参数，并以ＹＤ系列测力传感器为检测元件，建立了一套比较完善的自动检测系统。实验证明，用这套系统测出的结果比较准确地反映了冲击器的性能特点，对于研究和改进冲击器的结构具有指导意义，同时为研究冲击破岩机理提供了可靠的实验数据。