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.

     

Study on the Centralization Strategy of the Blood Allocation Among Different Departments within a Hospital

By far, the researches on how to distribute blood products among different departments in hospital have not been further studied, though the problem of blood shortage and wastage that caused by improper blood allocation is severe, which may endanger patient’s lives and impose considerable costs on hospitals. In order to solve this problem, this paper mainly studies on how to distribute the blood items among different departments within a hospital and investigates the allocation approach with the novel management method by centralizing the inventory of several different departments. By integrating the blood inventory requirements of some departments, the hospital could reduce the rate of blood shortage and wastage effectively, release the pressure of the occupancy of resources and reduce the bullwhip effect of blood products. This paper illustrates the centralization principle in hospital and formulates the mixed integer programming model to work out the optimal allocation network scheme and the optimal inventory setting for every department. And the results of the numerical example demonstrate that this centralization method could considerably reduce blood shortage and wastage in hospital by about 72% and 90% respectively. Furthermore, it could decrease the total cost by about 108,540 RMB a month on blood supply chain management in the hospital and improve the effect of some certain surgeries by transfusing the fresh blood to patients.     

广西高技术产业科技创新能力评价研究

文章在分析广西高技术产业发展现状基础上,构建高技术产业科技创新能力评价指标体系,运用熵值法,基于2015—2019年面板数据对广西高技术产业的创新能力进行实证研究.研究表明:广西高技术产业创新能力在西部五省中处于较低水平;广西高技术创新产出实力略低于创新投入实力,创新技术吸收实力仍相对较弱;广西高技术四大行业创新能力存在差异,即电子及通信设备制造产业科技创新投入和产出效果最好,医药制造业和电子通信及装备制造业创新投入高,创新产出评分偏低,医疗仪器设备及仪器仪表制造产业和计算机及办公设备制造产业创新吸收能力很弱.基于以上结论,文章从加大创新资源投入、推动创新平台建设、加强人才队伍建设等方面提出了对策建议.     

The modernity of Dedekind’s anticipations contained in What are numbers and what are they good for?

Archive for History of Exact Sciences - We show that Dedekind, in his proof of the principle of definition by mathematical recursion, used implicitly both the concept of an inductive cone from an...     

The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier

G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the “triple membrane bypass” pathway and the generation of reactive oxygen species. The recent recognition of GPCR transactivation of serine/threonine kinase receptors enormously broadens the GPCR signalling paradigm. It may be predicted that the transactivation of serine/threonine kinase receptors would have mechanistic similarities with transactivation of tyrosine kinase pathways; however, initial studies suggest that these two transactivation pathways are mechanistically distinct. Important questions are the relative importance of tyrosine and serine/threonine transactivation pathways, the contribution of transactivation to overall GPCR signalling, mechanisms of transactivation and the range of cell types in which this phenomenon occurs. The ultimate significance of transactivation-dependent signalling remains to be defined but it appears to be prominent and if so will represent a new cell signalling frontier.     

关于三网合一技术

介绍了我国现阶段并存的三网(电信网、有线电视网和计算机互联网)的特点与现状，分析了三网在融合过程中需要解决的一些不可避免的问题，以及三网合一的技术基础和促进三网合一的有利因素，提出了三网合一是现代通信和计算机网络发展的必然趋势，以及在三网融合的过程中还将有一个相互渗透交叉、相互竞争、共存发展过程的观点。