Secretagogues of lung surfactant increase annexin A7 localization with ABCA3 in alveolar type II cells

AbstractMembrane fusion between the lamellar bodies and plasma membrane is an obligatory event in the secretion of lung surfactant. Previous studies have postulated a role for annexin A7 (A7) in membrane fusion during exocytosis in some cells including alveolar type II cells. However, the intracellular trafficking of A7 during such fusion is not described. In this study, we investigated association of endogenous A7 with lamellar bodies in alveolar type II cells following treatment with several secretagogues of lung surfactant. Biochemical studies with specific antibodies showed increased membrane-association of cell A7 in type II cells stimulated with agents that increase secretion through different signaling mechanisms. Immuno-fluorescence studies showed increased co-localization of A7 with ABCA3, the lamellar body marker protein. Because these agents increase surfactant secretion through activation of PKC and PKA, we also investigated the effects of PKC and PKA inhibitors, bisindolylmaleimideI (BisI) and H89, respectively, on A7 partitioning. Western blot analysis showed that these inhibitors prevented secretagogue-mediated A7 increase in the membrane fractions. These inhibitors also blocked increased co-localization of A7 with ABCA3 in secretagogue-treated cells, as revealed by immuno-fluorescence studies. In vitro studies with recombinant A7 showed phosphorylation with PKC and PKA. The cell A7 was also phosphorylated in cells treated with surfactant secretagogues. Thus, our studies demonstrate that annexin A7 relocates to lamellar bodies in a phosphorylation-dependent manner. We suggest that activation of protein kinase promotes phosphorylation and membrane-association of A7 presumably to facilitate membrane fusion during lung surfactant secretion

Diabetes and oral therapies A review of oral therapies for diabetes mellitus

AbstractFor decades, antihyperglycaemic agents have been used for the treatment of type 2 diabetes mellitus given their effectiveness and convenience. Metformin (MET) and sulphonylureas (SU) are time-tested antihyperglycaemic agents that have been administered for more than 50 years. These agents were followed by the introduction of other antihyperglycaemic agents such as glinides (GLN), thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), dipeptidyl peptidase-4 inhibitors (DPP-4I), and sodium–glucose cotransporter-2 inhibitors (SGLT2I). MET is recognized as the drug of choice for monotherapy unless contraindicated or unwanted side effects occur. SU-induced hypoglycaemia is losing ground to various new agents, but the generic formulae of SU together with MET are cheap and effective. The cardiovascular hazards of several agents are a major concern to physicians and legislating bodies. In choosing antihyperglycaemic agents for dual or triple therapy, the treating physician must keep in mind the health status of the patient, medication side effects, cost, and patient preference. This review addresses the advantages and disadvantages of a range of antihyperglycaemic agents and their applications in monotherapy or combination therapy

Effect of Processing Parameters on Compressive Strength of Metakaolinite Based Geopolymers: Using DOE Approach

AbstractGeopolymers are inorganic materials with a wide variety of potential applications such as fire resistant materials, building materials, cements and concrete, high-tech composites aircraft interior, and etc. Various parameters affect the properties of these materials. This article describes the effects of several factors such as molar ratios of SiO2/Al2O3, Na2O/SiO2, and H2O/Na2O and curing temperature on the compressive strength of metakaolinite based geopolymer bodies (MGBs) by statistical design of experiments (DOE) approach. It was found that the above-mentioned agents play an important role in MGBs’ properties. Also, a model to present the relationship between compressive strength and influential factors was obtained

Addressing the Needs of Female Professional and Amateur Athletes

This study fills a major gap in the development of the dialogue around women's sports, a report that for the first time articulates female athletes' sense of the most pressing issues they face as competitors today. The results show that while many improvements have been made in U.S. women's sports, especially since the 1996 Olympic Games, there remains a consistent cluster of issues that needs to be addressed. This report outlines those issues and serves as the basis for policy recommendations and to facilitate communication about athletes' needs

A Methodology to Engineer and Validate Dynamic Multi-level Multi-agent Based Simulations

This article proposes a methodology to model and simulate complex systems, based on IRM4MLS, a generic agent-based meta-model able to deal with multi-level systems. This methodology permits the engineering of dynamic multi-level agent-based models, to represent complex systems over several scales and domains of interest. Its goal is to simulate a phenomenon using dynamically the lightest representation to save computer resources without loss of information. This methodology is based on two mechanisms: (1) the activation or deactivation of agents representing different domain parts of the same phenomenon and (2) the aggregation or disaggregation of agents representing the same phenomenon at different scales.Comment: Presented at 3th International Workshop on Multi-Agent Based Simulation, Valencia, Spain, 5th June 201

Bodies of Science and Law: Forensic DNA Profiling, Biological Bodies, and Biopower

How is jurisdiction transferred from an individual's biological body to agents of power such as the police, public prosecutor and judiciary, and what happens to these biological bodies when transformed from private into public objects? These questions are examined by analyzing bodies situated at the intersection of science and law. More specifically, the transformation of 'private bodies' into 'public bodies' shall be analyzed by going into the details of forensic DNA profiling in the Dutch jurisdiction. It will be argued that various 'forensic genetic practices' enact different 'forensic genetic bodies'. These enacted forensic genetic bodies are connected with various infringements of civil rights, which become articulated in exploring these forensic genetic bodies' 'normative registers'