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.     

建造合同预计损失准备的转回和转销

文章论述了建造合同完成前,在已计提了预计合同损失准备的情况下,对因完工百分比增加造成的预计损失准备变动额应采取的会计处理方式。     

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。     

基于PDM的集成化CAPP系统

讨论了基于产品数据管理的集成化CAPP系统的总体结构和模块结构 ,并对面向产品的工艺设计、IMAN与AutoCAD之间的通信、CAPP与MRPⅡ之间的集成、版本管理、流程管理、配置管理等关键技术进行了研究 .     

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。     

10kV油浸式变压器试验模态分析

针对变压器结构动力学优化设计问题,开展了10kV油浸式变压器试验模态分析。通过对变压器不同测点固有频率进行分析,并与变压器空载运行时相同测点振动信号对比发现：变压器长期运行后某些结构松动、老化会引起变压器固有频率变化;当变压器固有频率在工作频率附近时,可能引起变压器结构共振,影响变压器安全运行。本文研究结果为变压器结构性能优化分析和试验提供了一定参考。