Stabilization of dense Antarctic water supply to the Atlantic Ocean overturning circulation

The lower limb of the Atlantic overturning circulation is resupplied by the sinking of dense Antarctic Bottom Water (AABW) that forms via intense air–sea–ice interactions next to Antarctica, especially in the Weddell Sea. In the last three decades, AABW has warmed, freshened and declined in volume across the Atlantic Ocean and elsewhere, suggesting an ongoing major reorganization of oceanic overturning. However, the future contributions of AABW to the Atlantic overturning circulation are unclear. Here, using observations of AABW in the Scotia Sea, the most direct pathway from the Weddell Sea to the Atlantic Ocean, we show a recent cessation in the decline of the AABW supply to the Atlantic overturning circulation. The strongest decline was observed in the volume of the densest layers in the AABW throughflow from the early 1990s to 2014; since then, it has stabilized and partially recovered. We link these changes to variability in the densest classes of abyssal waters upstream. Our findings indicate that the previously observed decline in the supply of dense water to the Atlantic Ocean abyss may be stabilizing or reversing and thus call for a reassessment of Antarctic influences on overturning circulation, sea level, planetary-scale heat distribution and global climate

Attitudes towards community gambling venues and support for regulatory reform: An online panel study of residents in New South Wales, Australia

Background: Harmful gambling has been identified as an important public health issue that affects individuals, families and the broader community. One gambling product, electronic gambling machines (EGMs), has been associated with significant gambling harm in Australia. There has been limited research that has explored community perceptions of EGMs and attitudes towards reform. This study, conducted in NSW, Australia, aimed to explore community use of EGM venues (clubs and hotels containing EGMs), attitudes towards EGMs and whether the use of these venues influenced attitudes towards EGM reform. Methods: An online survey was conducted with 500 adults aged 16 years and over, representative of the population for age and gender. Discrete choice and open-ended questions were used to gather data on gambling behaviours, use of and attitudes towards EGMs and EGM venues and support for gambling harm reduction measures. Results: Three quarters of participants had visited an EGM venue in the previous year. Participants who had attended such venues were significantly more likely to use EGMs at least once per month. Participants attended EGM venues for a range of reasons including use of non-gambling facilities such as restaurants, the social aspects of the venue and ease of access to the venue. Some participants also attended EGM venues specifically for the gambling facilities. Most participants identified some negative impacts of EGMs for local communities and were supportive of measures to reduce the number of EGMs and prevent children's exposure to EGMs in such venues. Conclusions: This study shows a high level of support for EGM reform amongst both individuals who attend EGM venues and also those who do not. There is potential for government to further regulate EGMs and the environments where they are located

The Evolution of Robust Development and Homeostasis in Artificial Organisms

During embryogenesis, multicellular animals are shaped via cell proliferation, cell rearrangement, and apoptosis. At the end of development, tissue architecture is then maintained through balanced rates of cell proliferation and loss. Here, we take an in silico approach to look for generic systems features of morphogenesis in multicellular animals that arise as a consequence of the evolution of development. Using artificial evolution, we evolved cellular automata-based digital organisms that have distinct embryonic and homeostatic phases of development. Although these evolved organisms use a variety of strategies to maintain their form over time, organisms of different types were all found to rapidly recover from environmental damage in the form of wounds. This regenerative response was most robust in an organism with a stratified tissue-like architecture. An evolutionary analysis revealed that evolution itself contributed to the ability of this organism to maintain its form in the face of genetic and environmental perturbation, confirming the results of previous studies. In addition, the exceptional robustness of this organism to surface injury was found to result from an upward flux of cells, driven in part by cell divisions with a stable niche at the tissue base. Given the general nature of the model, our results lead us to suggest that many of the robust systems properties observed in real organisms, including scar-free wound-healing in well-protected embryos and the layered tissue architecture of regenerating epithelial tissues, may be by-products of the evolution of morphogenesis, rather than the direct result of selection

Self-assisted Amoeboid Navigation in Complex Environments

Background: Living cells of many types need to move in response to external stimuli in order to accomplish their functional tasks; these tasks range from wound healing to immune response to fertilization. While the directional motion is typically dictated by an external signal, the actual motility is also restricted by physical constraints, such as the presence of other cells and the extracellular matrix. The ability to successfully navigate in the presence of obstacles is not only essential for organisms, but might prove relevant in the study of autonomous robotic motion. Methodology/principal findings: We study a computational model of amoeboid chemotactic navigation under differing conditions, from motion in an obstacle-free environment to navigation between obstacles and finally to moving in a maze. We use the maze as a simple stand-in for a motion task with severe constraints, as might be expected in dense extracellular matrix. Whereas agents using simple chemotaxis can successfully navigate around small obstacles, the presence of large barriers can often lead to agent trapping. We further show that employing a simple memory mechanism, namely secretion of a repulsive chemical by the agent, helps the agent escape from such trapping. Conclusions/significance: Our main conclusion is that cells employing simple chemotactic strategies will often be unable to navigate through maze-like geometries, but a simple chemical marker mechanism (which we refer to as "self-assistance") significantly improves success rates. This realization provides important insights into mechanisms that might be employed by real cells migrating in complex environments as well as clues for the design of robotic navigation strategies. The results can be extended to more complicated multi-cellular systems and can be used in the study of mammalian cell migration and cancer metastasis

Attitudes towards community gambling venues and support for regulatory reform: an online panel study of residents in New South Wales, Australia

BACKGROUND: Harmful gambling has been identified as an important public health issue that affects individuals, families and the broader community. One gambling product, electronic gambling machines (EGMs), has been associated with significant gambling harm in Australia. There has been limited research that has explored community perceptions of EGMs and attitudes towards reform. This study, conducted in NSW, Australia, aimed to explore community use of EGM venues (clubs and hotels containing EGMs), attitudes towards EGMs and whether the use of these venues influenced attitudes towards EGM reform. METHODS: An online survey was conducted with 500 adults aged 16 years and over, representative of the population for age and gender. Discrete choice and open-ended questions were used to gather data on gambling behaviours, use of and attitudes towards EGMs and EGM venues and support for gambling harm reduction measures. RESULTS: Three quarters of participants had visited an EGM venue in the previous year. Participants who had attended such venues were significantly more likely to use EGMs at least once per month. Participants attended EGM venues for a range of reasons including use of non-gambling facilities such as restaurants, the social aspects of the venue and ease of access to the venue. Some participants also attended EGM venues specifically for the gambling facilities. Most participants identified some negative impacts of EGMs for local communities and were supportive of measures to reduce the number of EGMs and prevent children\u27s exposure to EGMs in such venues. CONCLUSIONS: This study shows a high level of support for EGM reform amongst both individuals who attend EGM venues and also those who do not. There is potential for government to further regulate EGMs and the environments where they are located

Creating symbolic cultures of consumption: an analysis of the content of sports wagering advertisements in Australia

Background: Since 2008, Australia has seen the rapid emergence of marketing for online and mobile sports wagering. Previous research from other areas of public health, such as tobacco and alcohol, has identified the range of appeal strategies these industries used to align their products with culturally valued symbols. However, there is very limited research that has investigated the tactics the sports wagering industry uses within marketing to influence the consumption of its products and services. Method: This study consisted of a mixed method interpretive content analysis of 85 sports wagering advertisements from 11 Australian and multinational wagering companies. Advertisements were identified via internet searches and industry websites. A coding framework was applied to investigate the extent and nature of symbolic appeal strategies within advertisements. Results: Ten major appeal strategies emerged from this analysis. These included sports fan rituals and behaviours; mateship; gender stereotypes; winning; social status; adventure, thrill and risk; happiness; sexualised imagery; power and control; and patriotism. Symbols relating to sports fan rituals and behaviours, and mateship, were the most common strategies used within the advertisements. Discussion/Conclusions: This research suggests that the appeal strategies used by the sports wagering industry are similar to those strategies adopted by other unhealthy commodity industries. With respect to gambling, analysis revealed that strategies are clearly targeted to young male sports fans. Researchers and public health practitioners should seek to better understand the impact of marketing on the normalisation of sports wagering for this audience segment, and implement strategies to prevent gambling harm

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

[Arg(6), D-Trp(7,9), N(me)Phe(8)]-substance P (6-11) (antagonist G) induces AP-1 transcription and sensitizes cells to chemotherapy.

[Arg(6), D-Trp(7,9), N(me)Phe(8)]-substance P (6-11) (antagonist G) inhibits small cell lung cancer (SCLC) growth and is entering Phase II clinical investigation for the treatment of SCLC. As well as acting as a neuropeptide receptor antagonist, antagonist G stimulates c-jun-N-terminal kinase (JNK) activity and apoptosis in SCLC cells. We extend these findings and show that the stimulation of JNK and apoptosis by antagonist G is dependent upon the generation of reactive oxygen species (ROS) being inhibited either by anoxia or the presence of N-acetyl cysteine (n-AC). Antagonist G is not intrinsically a free radical oxygen donor but stimulates free radical generation specifically within SCLC cells (6.2-fold) and increases the activity of the redox-sensitive transcription factor AP-1 by 61%. In keeping with this, antagonist G reduces cellular glutathione (GSH) levels (38% reduction) and stimulates ceramide production and lipid peroxidation (112% increase). At plasma concentrations achieved clinically in the phase I studies, antagonist G augments, more than additively, growth inhibition induced by etoposide. Our results suggest that antagonist G may be particularly effective as an additional treatment with standard chemotherapy in SCLC. These novel findings will be important for the clinical application of this new and exciting compound and for the future drug development of new agents to treat this aggressive cancer