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.

     

Investigation of MS and Anti-segregation Process HSS Flat Broaching Tools

An investigation has been carried out to compare th e cutting performance and tool life evaluation of high speed steel broach samp les. The comparison has been done between conventional M2 and Anti-Segregation Process (ASP) ASP53 and ASP30 high speed steel broach samples. The ASP53 was a development material. The cutting performance was evaluated by measuring the c utting forces and calculating the specific cutting energy, an indicator of cutti ng performance. As the roughness of the machined surfa...     

一种彩色图像的二维纹理识别方法

基于仿射矩正则化技术，推导出了新的光照仿射不变特征：Zernike矩、多波段相关函数，通过正则化方法实现仿射不变矩，采用组合矩方法和奇异值分解方法实现光照不变性，在推导光照不变性时必须使用复数值矩(如Zernike矩)，因为实数值仿射不变矩不能实现独立于光照变化的仿射不变性。实验结果表明，所提出的纹理识别方法具有很好的识别效果。     

Robust Adaptive Multi-Switching Synchronization of Multiple Different Orders Unknown Chaotic Systems

Multi-switching synchronization(MSS) of multiple different orders unknown chaotic(UC)systems confines hacking in the digital transmission process. Similarly, the suppression of undesirable chattering increases synchronization performance. This paper proposes a new robust synchronization control(RASC) technique and discusses the MSS of multiple different orders UC systems. This controller accomplishes(i) quick convergence,(ii) reduces the transient oscillations, and(iii) the rate of convergence decreases in the vicinity of the origin that causes the suppression of chattering. Analysis based on the Lyapunov direct method assures this convergence behavior with any positive values of the feedback gains. This work also provides parameters updated law that estimates the true values of unknown parameters. Numerical examples of five UC systems different orders are simulated. The computer based graphical results validate the efficiency and performance of the proposed RASC technique and the synchronization strategy when compare to peer works. In the simulation, the proposed synchronization strategy successfully recovers an encrypted received image on a communication channel.The article suggests some future research problems to extend the use of the proposed work.     

Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.     

LC-MS法测定拟南芥原生质体脱落酸的研究

利用高效液相色谱与质谱联用法(LC-MS法)对从土培拟南芥叶片和水培拟南芥根系中分离的原生质体进行脱落酸含量分析.结果表明,所测原生质体的脱落酸含量与原生质体数目之间具有较好的线性关系,相关系数分别为0.992 3和0.993 1.脱落酸含量的检测下限为1.07 ng/mL,土培拟南芥叶片和水培拟南芥根系原生质体检测下限分别为3万个和2万个.该研究以原生质体为材料,避免了细胞间隙中的复杂化学成干扰,提高了植物激素测定的灵敏度和精度,完善了经典的植物激素测定技术.     

Coral mucus functions as an energy carrier and particle trap in the reef ecosystem

Zooxanthellae, endosymbiotic algae of reef-building corals, substantially contribute to the high gross primary production of coral reefs, but corals exude up to half of the carbon assimilated by their zooxanthellae as mucus. Here we show that released coral mucus efficiently traps organic matter from the water column and rapidly carries energy and nutrients to the reef lagoon sediment, which acts as a biocatalytic mineralizing filter. In the Great Barrier Reef, the dominant genus of hard corals, Acropora, exudes up to 4.8 litres of mucus per square metre of reef area per day. Between 56% and 80% of this mucus dissolves in the reef water, which is filtered through the lagoon sands. Here, coral mucus is degraded at a turnover rate of at least 7% per hour. Detached undissolved mucus traps suspended particles, increasing its initial organic carbon and nitrogen content by three orders of magnitude within 2 h. Tidal currents concentrate these mucus aggregates into the lagoon, where they rapidly settle. Coral mucus provides light energy harvested by the zooxanthellae and trapped particles to the heterotrophic reef community, thereby establishing a recycling loop that supports benthic life, while reducing loss of energy and nutrients from the reef ecosystem.     

Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.     

Implementation Study Tree Computation on of Dynamic Load Balancing Algorithm of Parallel Clusters of Heterogeneous Workstation

The rapid growth of interconnected high performance workstations has produced a new computing paradigm called clustered of workstations computing. In these systems load balance problem is a serious impediment to achieve good performance. The main concern of this paper is the implementation of dynamic load balancing algorithm, asynchronous Round Robin （ARR）, for balancing workload of parallel tree computation depth-first-search algorithm on Cluster of Heterogeneous Workstations （ COW ） Many algorithms in artificial intelligence and other areas of computer science are based on depth first search in implicitty defined trees. For these algorithms a load- balancing scheme is required, which is able to evenly distribute parts of an irregularly shaped tree over the workstations with minimal interprocessor communication and without prior knowledge of the tree＇s shape. For the （ ARR ） algorithm only minimal interprocessor communication is needed when necessary and it runs under the MPI （Message passing interface） that allows parallel execution on heterogeneous SUN cluster of workstation platform. The program code is written in C language and executed under UNIX operating system （Solaris version）.