A Key Role for E-cadherin in Intestinal Homeostasis and Paneth Cell Maturation

E-cadherin is a major component of adherens junctions. Impaired expression of E-cadherin in the small intestine and colon has been linked to a disturbed intestinal homeostasis and barrier function. Down-regulation of E-cadherin is associated with the pathogenesis of infections with enteropathogenic bacteria and Crohn's disease. To genetically clarify the function of E-cadherin in intestinal homeostasis and maintenance of the epithelial defense line, the Cdh1 gene was conditionally inactivated in the mouse intestinal epithelium. Inactivation of the Cdh1 gene in the small intestine and colon resulted in bloody diarrhea associated with enhanced apoptosis and cell shedding, causing life-threatening disease within 6 days. Loss of E-cadherin led cells migrate faster along the crypt-villus axis and perturbed cellular differentiation. Maturation and positioning of goblet cells and Paneth cells, the main cell lineage of the intestinal innate immune system, was severely disturbed. The expression of anti-bacterial cryptidins was reduced and mice showed a deficiency in clearing enteropathogenic bacteria from the intestinal lumen. These results highlight the central function of E-cadherin in the maintenance of two components of the intestinal epithelial defense: E-cadherin is required for the proper function of the intestinal epithelial lining by providing mechanical integrity and is a prerequisite for the proper maturation of Paneth and goblet cells

Pigment epithelium-derived factor as an anticancer drug and new treatment methods following the discovery of its receptors: A patent perspective

Traditional forms of cancer therapy, which include chemotherapy, have largely been overhauled due to the significant degree of toxicity they pose to normal, otherwise healthy tissue. It is hoped that the use of biological agents, most of which are endogenously present in the body, will lead to safer treatment outcomes, without sacrificing efficacy. The finding that pigment epithelium-derived factor (PEDF), a naturally-occurring protein, is a potent angiogenesis inhibitor has become the basis for studying the role of PEDF in tumours that are highly resistant to chemotherapy. The determination of the direct role of PEDF against cancer paves the way for understanding and developing PEDF as a novel drug. This review focuses on the patent applications behind testing the anticancer therapeutic effect of PEDF via its receptors as an antiangiogenic agent and as a direct anticancer agent. The majority of the PEDF patents describe the antiangiogenic ability and usage of recombinant vectors as the mode of treatment delivery. PEDF's therapeutic potential against different diseases and the discovery of its receptors open possibilities for improving PEDF-based peptide design and drug delivery modes

The service quality-satisfaction link revisited: exploring asymmetries and dynamics

This study provides deeper insight in the link between service quality and customer satisfaction. The traditional assumption of a linear relationship is challenged by exploring asymmetries and dynamics. The simultaneous influence of service quality and customer experience on satisfaction is examined by means of nonlinear structural equation modeling. Results show that functional-utilitarian quality attributes (availability, efficiency, fulfillment, and privacy) lose their capability to delight customers as the customer relationship matures. In contrast, hedonic quality attributes (design, enjoyment, and image) only exhibit an increasing effect on satisfaction for more experienced customers. These insights are vital for service managers as they help to improve the efficiency of quality investments

Melting at the base of the Greenland ice sheet explained by Iceland hotspot history

Ice-penetrating radar1,2,3 and ice core drilling4 have shown that large parts of the north-central Greenland ice sheet are melting from below. It has been argued that basal ice melt is due to the anomalously high geothermal flux1,4 that has also influenced the development of the longest ice stream in Greenland1. Here we estimate the geothermal flux beneath the Greenland ice sheet and identify a 1,200-km-long and 400-km-wide geothermal anomaly beneath the thick ice cover. We suggest that this anomaly explains the observed melting of the ice sheet’s base, which drives the vigorous subglacial hydrology3 and controls the position of the head of the enigmatic 750-km-long northeastern Greenland ice stream5. Our combined analysis of independent seismic, gravity and tectonic data6,7,8,9 implies that the geothermal anomaly, which crosses Greenland from west to east, was formed by Greenland’s passage over the Iceland mantle plume between roughly 80 and 35 million years ago. We conclude that the complexity of the present-day subglacial hydrology and dynamic features of the north-central Greenland ice sheet originated in tectonic events that pre-date the onset of glaciation in Greenland by many tens of millions of years