Khumbi yullha and the Beyul: Sacred Space and the Cultural Politics of Religion in Khumbu, Nepal

Many parts of the Himalaya are at once indigenous people\u27s homelands, national parks or conservation areas, world-renowned trekking and mountaineering destinations, and the sites of ongoing ecological and socioeconomic development interventions. In addition, for many residents, protective territory deities reside in nearby peaks, and valleys between provide sacred places of refuge. Like in mountain regions elsewhere, these meanings represent overlapping and entwined claims of authority and territory from the state, indigenous communities, development agencies, and religious institutions. In this article I consider the ways in which resident Sherpas in Khumbu, Nepal, negotiate the overlapping spaces, authorities, and territories associated with understandings of the region as Khumbi yullha\u27s—a local deity—territory and the Nyingma Buddhist institutional claim to the region as a beyul—a sacred, hidden valley refuge, which development actors, both inside and outside the Khumbu Sherpa community, have attempted to mobilize as a sacred landscape supporting environmental conservation initiatives. Based on eighteen months of fieldwork in 2009 to 2010 and 2013, I focus on the spatiality of the cultural politics of religion in Khumbu in competing claims of territory from the Buddhist monastic institution and localized practices and the ways in which such constructions shape the outcomes of intervention programs

Tumour exosome integrins determine organotropic metastasis

Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α(6)β(4) and α(6)β(1) were associated with lung metastasis, while exosomal integrin α(v)β(5) was linked to liver metastasis. Targeting the integrins α(6)β(4) and α(v)β(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis