Endothelium-Derived Netrin-4 Supports Pancreatic Epithelial Cell Adhesion and Differentiation through Integrins α2β1 and α3β1

BACKGROUND: Netrins have been extensively studied in the developing central nervous system as pathfinding guidance cues, and more recently in non-neural tissues where they mediate cell adhesion, migration and differentiation. Netrin-4, a distant relative of Netrins 1-3, has been proposed to affect cell fate determination in developing epithelia, though receptors mediating these functions have yet to be identified. METHODOLOGY/PRINCIPAL FINDINGS: Using human embryonic pancreatic cells as a model of developing epithelium, here we report that Netrin-4 is abundantly expressed in vascular endothelial cells and pancreatic ductal cells, and supports epithelial cell adhesion through integrins α2β1 and α3β1. Interestingly, we find that Netrin-4 recognition by embryonic pancreatic cells through integrins α2β1 and α3β1 promotes insulin and glucagon gene expression. In addition, full genome microarray analysis revealed that fetal pancreatic cell adhesion to Netrin-4 causes a prominent down-regulation of cyclins and up-regulation of negative regulators of the cell cycle. Consistent with these results, a number of other genes whose activities have been linked to developmental decisions and/or cellular differentiation are up-regulated. CONCLUSIONS/SIGNIFICANCE: Given the recognized function of blood vessels in epithelial tissue morphogenesis, our results provide a mechanism by which endothelial-derived Netrin-4 may function as a pro-differentiation cue for adjacent developing pancreatic cell populations expressing adhesion receptors α2β1 and α3β1 integrins

Removal of endocrine-disrupting chemicals from textile industry effluents by nanofiltration

Textile finishing industry wastewaters contain micropollutants such as endocrine-disrupting chemicals in addition to the conventional pollutants since advanced manufacturing activities provide additional features to the textiles to make them shrink-proof, water-proof, wrinkle-proof, rot-proof, distasteful to moths, and mildew, flame-resistant, etc. Endocrine-disrupting chemicals can interfere with the endocrine system, exert endocrine-modulating behavior, and cause adverse health effects, even when exposed to low doses. Therefore, treatment of endocrine- disrupting chemicals is a major concern for textile finishing wastewaters since they cannot be completely removed by widely applied conventional treatment technologies; but rather by using membrane filtration, advanced oxidation, and adsorption technologies. This study aims to investigate the performance of nanofiltration membranes in the post-treatment of endocrine-disrupting chemicals in textile finishing wastewaters. A total of 299 chemicals that were identified as endocrine-disrupting chemicals present and/or likely to be present in surface waters of Turkey were monitored in a textile finishing wastewater, and their removal by nanofiltration was investigated. The experimental results showed that 10 of the 17 compounds determined in textile industry treatment plant effluent, including benzo (g,h,i) perylene, fluorene, phenanthrene, mono-2-ethylhexylphthalate, dicyclohexylphthalate, diethyl-phthalate, di-n-butylphthalate, octamethylcyclotetrasiloxane, mirex (perchloropentacyclodecane) and saccharin were treated below their limit of detection values with nanofiltration. On the other hand, it was determined that nanofiltration was not efficient for compounds such as naphthalene, mono-n-butylphthalate, and di-sec-octylphthalate

Role of insulin-like growth factor binding proteins in mammary gland development

Insulin-like growth factors (IGFs) play an important role in mammary gland development and their effects are, in turn, influenced by a family of 6 IGF-binding proteins (IGFBPs). The IGFBPs are expressed in time- and tissue-specific fashion during the periods of rapid growth and involution of the mammary gland. The precise roles of these proteins in vivo have, however, been difficult to determine. This review examines the indirect evidence (evolution, chromosomal location and roles in lower life-forms) the evidence from in vitro studies and the attempts to examine their roles in vivo, using IGFBP-deficient and over-expression models. Evidence exists for a role of the IGFBPs in inhibition of the survival effects of IGFs as well as in IGF-enhancing effects from in vitro studies. The location of the IGFBPs, often associated with the extracellular matrix, suggests roles as a reservoir of IGFs or as a potential barrier, restricting access of IGFs to distinct cellular compartments. We also discuss the relative importance of IGF-dependent versus IGF-independent effects. IGF-independent effects include nuclear localization, activation of proteases and interaction with a variety of extracellular matrix and cell surface proteins. Finally, we examine the increasing evidence for the IGFBPs to be considered as part of a larger family of extracellular matrix proteins involved in morphogenesis and tissue re-modeling

Prophylactic antibiotic regimens in tumour surgery (PARITY) A PILOT MULTICENTRE RANDOMISED CONTROLLED TRIAL

Optimising joint reconstruction management in arthritis and bone tumour patient