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.

     

An Economic Model-Based Matching Approach Between Buyers and Sellers Through a Broker in an Open E-Marketplace

A broker in an open e-marketplace enables buyers and sellers to do business with each other. Although a broker plays an important role in e-marketplaces, theory and guidelines for matching between buyers and sellers in multi-attribute exchanges are limited. Therefore, a challenge for a broker’s responsibility is how to maximize a buyer’s total satisfaction degree as its goals under the consideration of trade-off between a buyer’s buying quantity and price paid to a seller, and other attributes. To solve this challenge, this paper proposes an economic model-based matching approach between a buyer’s requirements and a seller’s offers. The major contributions of this paper are that (i) a broker can model a seller’s price policy as per a buyer’s buying quantity through communication between a broker and a seller; (ii) due to each buyer’s different quantity demand, a broker models a buyer’s satisfaction degree as per a buyer’s buying quantity based on communication between a broker and a buyer; and (iii) to carry out a broker’s matching processes, an objective function and a set of constraints are generated to help a broker to maximize a buyer’s total satisfaction degree. Experimental results demonstrate the good performance of the proposed approach.     

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.     

Effects of Strain Rate,Temperature and Grain Size on the Mechanical Properties and Microstructure Evolutions of Polycrystalline Nickel Nanowires: A Molecular Dynamics Simulation

Through molecular dynamics(MD)simulation,the dependencies of temperature,grain size and strain rate on the mechanical properties were studied.The simulation results demonstrated that the strain rate from 0.05 to 2 ns~(–1 )affected the Young’s modulus of nickel nanowires slightly,whereas the yield stress increased.The Young’s modulus decreased approximately linearly;however,the yield stress firstly increased and subsequently dropped as the temperature increased.The Young’s modulus and yield stress increased as the mean grain size increased from 2.66 to6.72 nm.Moreover,certain efforts have been made in the microstructure evolution with mechanical properties association under uniaxial tension.Certain phenomena such as the formation of twin structures,which were found in nanowires with larger grain size at higher strain rate and lower temperature,as well as the movement of grain boundaries and dislocation,were detected and discussed in detail.The results demonstrated that the plastic deformation was mainly accommodated by the motion of grain boundaries for smaller grain size.However,for larger grain size,the formations of stacking faults and twins were the main mechanisms of plastic deformation in the polycrystalline nickel nanowire.     

Fuzzy Views on Black-Litterman Portfolio Selection Model

In this paper, views of investor are described in fuzzy sets, and two fuzzy Black-Litterman models are constructed with fuzzy views and fuzzy random views respectively. In the models, expected returns and uncertainty matrix of views are redefined and the views are formulated by fuzzy approaches suitably. Then the models are tested with data from Chinese financial markets. Empirical results show that the fuzzy random views model performs the best, and both the fuzzy models are better than the traditional ones, demonstrating that the fuzzy approaches can contain more information in the views and measure the uncertainty more correctly.     

The growth plate’s response to load is partially mediated by mechano-sensing via the chondrocytic primary cilium

Mechanical load plays a significant role in bone and growth-plate development. Chondrocytes sense and respond to mechanical stimulation; however, the mechanisms by which those signals exert their effects are not fully understood. The primary cilium has been identified as a mechano-sensor in several cell types, including renal epithelial cells and endothelium, and accumulating evidence connects it to mechano-transduction in chondrocytes. In the growth plate, the primary cilium is involved in several regulatory pathways, such as the non-canonical Wnt and Indian Hedgehog. Moreover, it mediates cell shape, orientation, growth, and differentiation in the growth plate. In this work, we show that mechanical load enhances ciliogenesis in the growth plate. This leads to alterations in the expression and localization of key members of the Ihh-PTHrP loop resulting in decreased proliferation and an abnormal switch from proliferation to differentiation, together with abnormal chondrocyte morphology and organization. Moreover, we use the chondrogenic cell line ATDC5, a model for growth-plate chondrocytes, to understand the mechanisms mediating the participation of the primary cilium, and in particular KIF3A, in the cell’s response to mechanical stimulation. We show that this key component of the cilium mediates gene expression in response to mechanical stimulation.     

Ciliary proteins Fap43 and Fap44 interact with each other and are essential for proper cilia and flagella beating

Cilia beating is powered by the inner and outer dynein arms (IDAs and ODAs). These multi-subunit macrocomplexes are arranged in two rows on each outer doublet along the entire cilium length, except its distal end. To generate cilia beating, the activity of ODAs and IDAs must be strictly regulated locally by interactions with the dynein arm-associated structures within each ciliary unit and coordinated globally in time and space between doublets and along the axoneme. Here, we provide evidence of a novel ciliary complex composed of two conserved WD-repeat proteins, Fap43p and Fap44p. This complex is adjacent to another WD-repeat protein, Fap57p, and most likely the two-headed inner dynein arm, IDA I1. Loss of either protein results in altered waveform, beat stroke and reduced swimming speed. The ciliary localization of Fap43p and Fap44p is interdependent in the ciliate Tetrahymena thermophila.