Expression of Cathepsins B, D, and G in WHO Grade I Meningioma

Aim: We have recently demonstrated the presence of putative tumor stem cells (TSCs) in World Health Organization (WHO) grade I meningioma (MG) localized to the microvessels, which expresses components of the renin-angiotensin system (RAS). The RAS is known to be dysregulated and promotes tumorigenesis in many cancer types, including glioblastoma. Cathepsins B, D, and G are isoenzymes that catalyze the production of angiotensin peptides, hence providing bypass loops for the RAS. This study investigated the expression of cathepsins B, D, and G in WHO grade I MG in relation to the putative TSC population we have previously demonstrated.Methods: 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining with antibodies for cathepsins B, D, and G was performed on WHO grade I MG tissue samples from 10 patients. Three of the MG samples subjected to DAB IHC staining underwent immunofluorescence (IF) IHC staining to investigate co-expression of each of these cathepsins using combinations of smooth muscle actin (SMA) and embryonic stem cell marker OCT4. NanoString mRNA expression (n = 6) and Western blotting (WB; n = 5) analyses, and enzyme activity assays (EAAs; n = 3), were performed on snap-frozen WHO grade I MG tissue samples to confirm transcriptional activation, protein expression, and functional activity of these proteins, respectively.Results: DAB IHC staining demonstrated expression of cathepsins B, D, and G in all 10 MG samples. NanoString mRNA expression and WB analyses showed transcriptional activation and protein expression of all three cathepsins, although cathepsin G was expressed at low levels. EAAs demonstrated that cathepsin B and cathepsin D were functionally active. IF IHC staining illustrated localization of cathepsin B and cathepsin D to the endothelium and SMA+ pericyte layer of the microvessels, while cathepsin G was localized to cells scattered within the interstitium, away from the microvessels.Conclusion: Cathepsin B and cathepsin D, and to a lesser extent cathepsin G, are expressed in WHO grade I MG. Cathepsin B and cathepsin D are enzymatically active and are localized to the putative TSC population on the microvessels, whereas cathepsin G was localized to cells scattered within the interstitium, These results suggest the presence of bypass loops for the RAS, within WHO grade I MG

Effectiveness of evacuation facilities in Honiara City, Solomon Islands: a spatial perspective

Urban areas in South Pacific island countries are experiencing the effects of natural disasters related to extreme weather events, cyclones and flooding. The aim of this study was to evaluate 27 existing evacuation facilities in Honiara City and nearby areas from a spatial perspective. We use the concept of “service areas” to determine whether a given facility, or all facilities taken collectively, is accessible to the populations within its geographic proximity. To determine geographic proximity we use the network analysis capabilities of a geographic information system (GIS) to establish service areas. Service areas are defined as the area within which people can reach a facility along a road network in a given amount of time based on the cost, or impedance, of travel along the network. Using this approach we use the overlay capabilities of the GIS to estimate the percentage of each facility’s service area that “captures” the populations, or areas, in greatest need. With GIS census data, road network data, flood hazard data, and evacuation facility data from the recent April 2014 extreme weather event, we examine the relative effectiveness of the existing facilities. We focus on disasters associated with severe weather, especially flooding and storm surge. Our analysis suggests that the 27 existing evacuation facilities in Honiara and nearby areas taken collectively provide reasonably good coverage of those populations in greatest need in a flooding or storm surge event. However we also find some facilities are poorly located and subsequently under used