‘It's like the bad guy in a movie who just doesn't die’ : a qualitative exploration of young people's adaptation to eczema and implications for self‐care

Background Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children ‘outgrow eczema’, although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course. Objectives To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self‐care and adapting to living with eczema. Methods This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old. Results Participants generally experienced eczema as an episodic long‐term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self‐care, challenging the process of identifying triggers of eczema flare‐ups and evaluating the success of treatment regimens. Participants’ experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from ‘cure’ to ‘control’ of eczema. Conclusions For young people who continue to experience eczema beyond childhood, a greater focus on self‐care for a long‐term condition may be helpful. Greater awareness of the impact of early messages around ‘growing out of’ eczema and provision of high‐quality information may help patients to manage expectations and support adaptation to treatment regimens

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

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 A$21.78 in a one‐off levy. The aggregate value calculated for households in the basin's jurisdictions was A$74.5 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

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

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

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

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

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

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

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

Distinct Dynamics of Endocytic Clathrin-Coated Pits and Coated Plaques

Here we classify endocytic structures at the adherent (bottom) surface of many cells in culture into shorter-lived coated pits and longer-lived coated plaques which internalize by different mechanisms

Pollen, biomarker and stable isotope evidence of late Quaternary environmental change at Lake McKenzie, southeast Queensland

Unravelling links between climate change and vegetation response during the Quaternary is important if the climate–environment interactions of modern systems are to be fully understood. Using a sediment core from Lake McKenzie, Fraser Island, we reconstruct changes in the lake ecosystem and surrounding vegetation over the last ca. 36.9 cal kyr. Evidence is drawn from multiple sources, including pollen, micro-charcoal, biomarker and stable isotope (C and N) analyses, and is used to gain a better understanding of the nature and timing of past ecological changes that have occurred at the site. The glacial period of the record, from ca. 36.9 to 18.3 cal kyr BP, is characterised by an increased abundance of plants of the aquatic and littoral zone, indicating lower lake water levels. High abundance of biomarkers and microfossils of the colonial green alga Botryococcus occurred at this time and included large variation in individual botryococcene d13C values. A slowing or ceasing of sediment accumulation occurred during the time period from ca. 18.3 to 14.0 cal kyr BP. By around 14.0 cal kyr BP fire activity in the area was reduced, as was abundance of littoral plants and terrestrial herbs, suggesting wetter conditions from that time. The Lake McKenzie pollen record conforms to existing records from Fraser Island by containing evidence of a period of reduced effective precipitation that commenced in the mid-Holocene

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

<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

Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

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