148 research outputs found

    Public attitudes to inequality in water distribution: Insights from preferences for water reallocation from irrigators to Aboriginal Australians

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    Water allocation regimes that adjudicate between competing uses are in many countries under pressure to adapt to increasing demands, climate‐driven shortages, expectations for equity of access, as well as societal changes in values and priorities. International authorities expound standards for national allocation regimes that include robust processes for addressing the needs of ‘new entrants' and for varying existing entitlements within sustainable limits. The claims of Indigenous peoples to water represents a newly recognised set of rights and interests that will test the ability of allocation regimes to address the global water governance goal of equity. No study has sought to identify public attitudes or willingness to pay for a fairer allocation of water rights between Indigenous and non‐Indigenous people. We surveyed households from the jurisdictions of Australia's Murray‐Darling Basin, a region undergoing a historic government‐led recovery of water, and found that 69.2% of respondents support the principle of reallocating a small amount of water from irrigators to Aboriginal people via the water market. Using contingent valuation, we estimated households are willing to pay A21.78inaoneofflevy.TheaggregatevaluecalculatedforhouseholdsinthebasinsjurisdictionswasA21.78 in a one‐off levy. The aggregate value calculated for households in the basin's jurisdictions was A74.5 million, which is almost double a recent government commitment to fund the acquisition of entitlements for Aboriginal nations of this basin. Results varied by state of residency and affinity with environmental groups. An information treatment that presented narrative accounts from Aboriginal people influenced the results. Insights from this study can inform water reallocation processes

    The role of clathrin in post-golgi trafficking in toxoplasma gondii

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    Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

    Complex history of dog (Canis familiaris) origins and translocations in the Pacific revealed by ancient mitogenomes

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    Archaeological evidence suggests that dogs were introduced to the islands of Oceania via Island Southeast Asia around 3,300 years ago, and reached the eastern islands of Polynesia by the fourteenth century AD. This dispersal is intimately tied to human expansion, but the involvement of dogs in Pacific migrations is not well understood. Our analyses of seven new complete ancient mitogenomes and five partial mtDNA sequences from archaeological dog specimens from Mainland and Island Southeast Asia and the Pacific suggests at least three dog dispersal events into the region, in addition to the introduction of dingoes to Australia. We see an early introduction of dogs to Island Southeast Asia, which does not appear to extend into the islands of Oceania. A shared haplogroup identified between Iron Age Taiwanese dogs, terminal-Lapita and post-Lapita dogs suggests that at least one dog lineage was introduced to Near Oceania by or as the result of interactions with Austronesian language speakers associated with the Lapita Cultural Complex. We did not find any evidence that these dogs were successfully transported beyond New Guinea. Finally, we identify a widespread dog clade found across the Pacific, including the islands of Polynesia, which likely suggests a post-Lapita dog introduction from southern Island Southeast Asia

    Full Spectrum Archaeology

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    Full Spectrum Archaeology (FSA) is an aspiration stemming from the convergence of archaeology’s fundamental principles with international heritage policies and community preferences. FSA encompasses study and stewardship of the full range of heritage resources in accord with the full range of associated values and through the application of treatments selected from the full range of appropriate options. Late modern states, including British Columbia, Canada, nominally embrace de jure heritage policies consonant with international standards yet also resist de facto heritage management practice grounded in professional ethics and local values and preferences. In response, inheritor communities and their allies in archaeology are demonstrating the benefits of FSA and reclaiming control over cultural heritage. Archaeology and heritage management driven by altruistic articulation of communal, educational, scientific and other values further expose shortcomings and vulnerabilities of late modern states as well as public goods in and from FSA

    Using Ethnographic Methods to Articulate Community-Based Conceptions of Cultural Heritage Management

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    How can ethnographic methods help communities articulate and enact their own conceptions of heritage management? This and related questions are being explored through an international research project, ‘Intellectual Property Issues in Cultural Heritage’. The project includes up to twenty community- based initiatives that incorporate community-based participatory research and ethnographic methods to explore emerging intellectual property-related issues in archaeological contexts; the means by which they are being addressed or resolved; and the broader implications of these issues and concerns. We discuss three examples that use ethnography to (a) articulate local or customary laws and principles of archaeological heritage management among a First Nations group in British Columbia; (b) assemble knowledge related to land/sea use and cultural practices of the Moriori people of Rekohu (Chatham Islands) for their use in future land and heritage manage- ment policies; and (c) aid a tribal cultural centre in Michigan in crafting co-management strategies to protect spiritual traditions associated with a rock art site on state property. Such situations call for participatory methods that place control over the design, process, products, and interpretation of ‘archaeology’ in the hands of cultural descendants. We hope that these examples of community-based conceptions of archaeological heritage management, facilitated through ethnographic methods and participatory approaches, will increase awareness of the value of these and other alternative approaches and the need to share them widely

    Prognostic significance of cortactin levels in head and neck squamous cell carcinoma: comparison with epidermal growth factor receptor status

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    Cortactin is an actin-binding Src substrate involved in cell motility and invasion. In this study, we sought to examine the prognostic importance of cortactin protein expression in head and neck squamous cell carcinoma (HNSCC). To do so, cortactin and EGF receptor (EGFR) expression was retrospectively evaluated by immunohistochemistry in a tissue microarray composed of 176 HNSCCs with a mean follow-up time of 5 years. Cortactin immunoreactivity was weak to absent in normal epithelial tissue. Overexpression of the protein in 77 out of 176 tumours (44%) was associated with more advanced tumour-node-metastasis stage and higher histologic grade. Cortactin overexpression was associated with significantly increased local recurrence rates (49 vs 28% for high and low expressing carcinomas, respectively), decreased disease-free survival (17 vs 61%), and decreased the 5-year overall survival of (21 vs 58%), independently of the EGFR status. In multivariate analysis, cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. Importantly, we identified a subset of patients with cortactin-overexpressing tumours that displayed low EGFR levels and a survival rate that equalled that of patients with tumoral overexpression of both EGFR and cortactin. These findings identify cortactin as a relevant prognostic marker and may have implications for targeted therapies in patients with HNSCC

    Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

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    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1) a common molecular pathway underlying these different neuromuscular diseases, and (2) tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches

    Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

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    <p>Abstract</p> <p>Background</p> <p>Nck1 and Nck2 adaptor proteins are involved in signaling pathways mediating proliferation, cytoskeleton organization and integrated stress response. Overexpression of Nck1 in fibroblasts has been shown to be oncogenic. Through the years this concept has been challenged and the consensus is now that overexpression of either Nck cooperates with strong oncogenes to transform cells. Therefore, variations in Nck expression levels in transformed cells could endorse cancer progression.</p> <p>Methods</p> <p>Expression of Nck1 and Nck2 proteins in various cancer cell lines at different stages of progression were analyzed by western blots. We created human primary melanoma cell lines overexpressing GFP-Nck2 and investigated their ability to proliferate along with metastatic characteristics such as migration and invasion. By western blot analysis, we compared levels of proteins phosphorylated on tyrosine as well as cadherins and integrins in human melanoma cells overexpressing or not Nck2. Finally, in mice we assessed tumor growth rate of human melanoma cells expressing increasing levels of Nck2.</p> <p>Results</p> <p>We found that expression of Nck2 is consistently increased in various metastatic cancer cell lines compared with primary counterparts. Particularly, we observed significant higher levels of Nck2 protein and mRNA, as opposed to no change in Nck1, in human metastatic melanoma cell lines compared with non-metastatic melanoma and normal melanocytes. We demonstrated the involvement of Nck2 in proliferation, migration and invasion in human melanoma cells. Moreover, we discovered that Nck2 overexpression in human primary melanoma cells correlates with higher levels of proteins phosphorylated on tyrosine residues, assembly of Nck2-dependent pY-proteins-containing molecular complexes and downregulation of cadherins and integrins. Importantly, we uncovered that injection of Nck2-overexpressing human primary melanoma cells into mice increases melanoma-derived tumor growth rate.</p> <p>Conclusions</p> <p>Collectively, our data indicate that Nck2 effectively influences human melanoma phenotype progression. At the molecular level, we propose that Nck2 in human primary melanoma promotes the formation of molecular complexes regulating proliferation and actin cytoskeleton dynamics by modulating kinases or phosphatases activities that results in increased levels of proteins phosphorylated on tyrosine residues. This study provides new insights regarding cancer progression that could impact on the therapeutic strategies targeting cancer.</p

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

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