Expression of peptide YY in all four islet cell types in the developing mouse pancreas suggests a common peptide YY-producing progenitor

The islets of Langerhans contain four distinct endocrine cell types producing the hormones glucagon, insulin, somatostatin and pancreatic polypeptide. These cell lineages are thought to arise from a common, multipotential progenitor cell whose identity has not been well established. The pancreatic and intestinal hormone, peptide YY, has been previously identified in glucagon-producing cells in islets; however, transgenic mice expressing Simian Virus 40 large T antigen under the control of the peptide YY gene expressed the oncoprotein in beta, delta and pancreatic polypeptide cells, and occasionally developed insulinomas, suggesting relationships between peptide YY-producing cells and several islet cell lineages. The four established pancreatic islet cell types were examined for coexpression of peptide YY in islets of normal and transgenic mice throughout development. Peptide YY immunoreactivity was identified in the earliest endocrine cells in the fetal pancreas and was coexpressed in each islet cell type during development. Peptide YY showed a high degree of co-localization with glucagon- and insulin-producing cells in early pancreatic development, but by adulthood, peptide YY was expressed in less than half of the alpha cells and was no longer expressed in beta cells. Peptide YY was also coexpressed with somatostatin and pancreatic polypeptide when these cell types first appeared, but most delta and pancreatic polypeptide cells continued to express peptide YY throughout development. The use of conditions that distinguish peptide YY from the related peptides, pancreatic polypeptide and neuropeptide Y, as well as the ability of the peptide YY gene to direct expression of a reporter gene in islets of transgenic mice, establishes expression of peptide YY in the earliest pancreatic endocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Production and Characterization of Peptide Antibodies to the C-Terminal of Frameshifted Calreticulin Associated with Myeloproliferative Diseases

Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys¹, Trp⁹, and Glu¹¹ were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets.     

An Investigation into the Powder Release Behavior from Capsule-Based Dry Powder Inhalers

A methodology for studying the deagglomeration performance and emptying behavior of micronized mannitol powder from two commercial capsule-based dry powder inhalers (DPIs), the low- and high-resistance RS01®, is presented. Mathematical modeling played a key role in the interpretation of the powder release behavior from these two DPI systems. Non-linear regression models, which were characterized from the aerosol obscuration versus time profiles obtained from laser diffraction particle sizing data, were used to estimate rate constants for emptying of mannitol powder. The effects of device resistance and associated pressure drops, sampling flow rate, rates of powder emptying, and the presence of capsule on the dispersion characteristics were studied. The presence of a capsule significantly improved the aerosolization performance of mannitol powder from both inhalers, which may be due to the extended powder–air–device interactions within the device. It is important to consider the stochastic nature of movement and physical state of the capsule when assessing the aerosolization mechanisms and dispersion performance from these complex delivery systems. The methodology set out in this study has the capacity to provide a greater level of detail in the study of aerosol plume characteristics from capsule-based DPIs.

Copyright 2015 American Association for Aerosol Research     

Crystal plasticity investigation of friction effect on texture evolution of Al single crystal during ECAP

A crystal plasticity finite element model has been developed to study the effect of friction between the die wall and the billet on texture evolution during equal channel angular pressing of an aluminum single crystal. Four cases with different coefficients of friction μ = 0, 0.05, 0.1, and 0.15 have been simulated. It has been found that the friction of μ = 0.05 and 0.1 can capture the major texture features shown in the experimental results, and μ = 0.05 predicts a slightly better texture than μ = 0.1. The frictional condition significantly affects texture evolution in the region between 1/2 and 3/4 of the billet thickness from the top surface. It can be attributed to the effect of friction on the corner gap and the distribution of stresses in the die corner.