The Nakanai Mountain Ranges of East New Britain Papua New Guinea. E: Booklet Version 2

NOTES ON THE E-BOOKLET VERSION TWO Between 2016- 2019, a multidisciplinary team of researchers1 from Australia and Papua New Guinea worked in collaboration with local communities to document the cultural values of the Nakanai Mountains and their inextricable link to the spectacular natural landscape. This research aims to contribute to a standalone nomination to the UNESCCO Tentative World Heritage List of the Nakanai Karst Area (NKA) and elevate its recognition as a cultural landscape of outstanding significance. The research team included both anthropologists and archaeologists. Further anthropological and archaeological research is likely to yield further evidence of the richly diverse cultural values of the area. Between July 2018 - December 2019, researchers from James Cook University (JCU) in collaboration with postgraduate researchers from the University of Papua New Guinea (UPNG) were commissioned by the United Nations Development Programme2 in conjunction with the Conservation, Environment Protection Authority to generate awareness of protected area planning processes and to facilitate the gazettal of four Community Protected Areas around Jacquinot Bay and Central Inland Pomio. These protected area processes are ongoing

Beta1 integrin activation inhibits in vitro tube formation: effects on cell migration, vacuole coalescence and lumen formation

Human endothelial cells (EC), when plated onto gels of extracellular matrix proteins such as Matrigel or collagen form capillary tubes in a process thought to mimic angiogenesis. We have shown previously that the extent of tube formation and the phenotype of the lumen are regulated by integrins (Gamble et al 1993) and lumen formation occurs through a process of vacuolization, coalescence and ultimate directional fusion of these vacuoles with the plasma membrane (Meyer 1997 et al). We now show here that activation of β1 integrins on endothelial cells inhibits tube formation. On collagen gels, endothelial cells treated with β1 activating antibody 8A2 failed to migrate into the gel and tube formation was inhibited. Although several integrins mediate EC attachment to collagen α2β1 is the chief determinant of EC behaviour since a blocking antibody to α2β1 reversed the effect of 8A2. On Matrigel tube formation was also inhibited by 8A2 treatment although cell alignment and sprout formation was still evident. Electron microscopy revealed the organisation of normal numbers of cells into solid sprouts and the formation of small intracellular vacuoles suggesting that initial stages of tube formation including cell migration were unaffected. However, β1 integrin activation inhibited the coalescence of these small vacuoles into larger vacuoles, the recruitment of more cells into the sprout and the subsequent formation of mature lumen. The inhibition of capillary tube formation by β1 activation was time dependent and long lasting. The critical time for activation of the β1 integrin was the initial 1–2h after plating in order to inhibit tube formation although once activated, the β1 mediated inhibition on Matrigel was still evident 4 days later. Our results suggest that β1 integrins are critical in capillary tube formation in at least two phases, β1 integrins are essential for migration of EC through collagen gels. Independently, β1 integrins, although not involved in initial vacuole formation, are involved in the process of vacuole coalescence and subsequent lumen formation since β1 integrin activation inhibits these processes.Jennifer Gamble, Geoff Meyer, Leanne Noack, Jill Furze, Lisa Matthias, Nickolas Kovach, John Harlan, Mathew Vadashttp://informahealthcare.com/doi/abs/10.3109/1062332990916530

Chronic increases in sphingosine kinase-1 activity induce a pro-inflammatory, pro-angiogenic phenotype in endothelial cells

Sphingosine kinase-1 (SK1) promotes the formation of sphingosine-1-phosphate (S1P), which has potent pro-inflammatory and pro-angiogenic effects. We investigated the effects of raised SK1 levels on endothelial cell function and the possibility that this signaling pathway is activated in rheumatoid arthritis. Human umbilical vein endothelial cells with 3- to 5-fold SK1 (EC(SK)) overexpression were generated by adenoviral and retroviralmediated gene delivery. The activation state of these cells and their ability to undergo angiogenesis was determined. S1P was measured in synovial fluid from patients with RA and OA. EC(SK) showed an enhanced migratory capacity and a stimulated rate of capillary tube formation. The cells showed constitutive activation as evidenced by the induction of basal VCAM-1 expression, and further showed a more augmented VCAM-1 and E selectin response to TNF compared with empty vector control cells (EC(EV)). These changes had functional consequences in terms of enhanced neutrophil binding in the basal and TNFstimulated states in EC(SK). By contrast, over-expression of a dominant-negative SK inhibited the TNF-induced VCAM-1 and E selectin and inhibited PMN adhesion, confirming that the observed effects were specifically mediated by SK. The synovial fluid levels of S1P were significantly higher in patients with RA than in those with OA. Small chronic increases in SK1 activity in the endothelial cells enhance the ability of the cells to support inflammation and undergo angiogenesis, and sensitize the cells to inflammatory cytokines. The SK1 signaling pathway is activated in RA, suggesting that manipulation of SK1 activity in diseases of aberrant inflammation and angiogenesis may be beneficial.Vidya Limaye, Pu Xia, Chris Hahn, Malcolm Smith, Mathew A. Vadas, Stuart M. Pitson and Jennifer R. Gambl

Phenoxodiol, an experimental anticancer drug, shows potent antiangiogenic properties in addition to its antitumour effects

Phenoxodiol (2H-1-benzopyran-7-0,1, 3-[4-hydroxyphenyl], PXD) is a synthetic analogue of the naturally-occurring plant isoflavone and anticancer agent, genistein. PXD directly induces mitotic arrest and apoptosis in most cancer cells and is currently undergoing clinical trials, as a chemotherapeutic in ovarian and prostate cancers. We show here that PXD also exhibits potent antiangiogenic properties. Thus, it inhibited endothelial cell proliferation, migration and capillary tube formation and inhibited expression of the matrix metalloproteinase MMP-2, a major matrix degrading enzyme. Importantly, we demonstrate that PXD is functional in vivo since it inhibited the extent of capillary tube invasion in an in vivo model of angiogenesis. We show that phenoxodiol inhibits hallmarks of endothelial cell activation, namely TNF or IL-1 induced E-selectin and VCAM-1 expression and IL-8 secretion. However, PXD had no effect on unstimulated endothelial cells. We also describe that PXD inhibits the lipid kinase sphingosine kinase, which recently has been implicated in endothelial cell activation and angiogenesis as well as oncogenesis. Thus, our results suggest that PXD may be an effective anticancer drug targeting the two drivers of tumour growth--the proliferation of the tumour cells themselves and the angiogenic and inflammatory stimulation of the vasculature.Gamble, Jennifer R. ; Xia, Pu ; Hahn, Christopher N. ; Drew, Jenny J. ; Drogemuller, Christopher J. ; Brown, David ; Vadas, Mathew A