54 research outputs found

    Assessing Sustainable Food and Nutrition Security of the EU Food System—An Integrated Approach

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    Steering the EU food system towards a sustainability transformation requires a vast and actionable knowledge base available to a range of public and private actors. Few have captured this complexity by assessing food systems from a multi-dimensional and multi-level perspective, which would include (1) nutrition and diet, environmental and economic outcomes together with social equity dimensions and (2) system interactions across country, EU and global scales. This paper addresses this gap in food systems research and science communication by providing an integrated analytical approach and new ways to communicate this complexity outside science. Based on a transdisciplinary science approach with continuous stakeholder input, the EU Horizon2020 project ‘Metrics, Models and Foresight for European SUStainable Food And Nutrition Security’ (SUSFANS) developed a five-step process: Creating a participatory space; designing a conceptual framework of the EU food system; developing food system performance metrics; designing a modelling toolbox and developing a visualization tool. The Sustainable Food and Nutrition-Visualizer, designed to communicate complex policy change-impacts and trade-off questions, enables an informed debate about trade-offs associated with options for change among food system actors as well as in the policy making arena. The discussion highlights points for further research related to indicator development, reach of assessment models, participatory processes and obstacles in science communication

    A Gain-of-Function Germline Mutation in Drosophila ras1 Affects Apoptosis and Cell Fate during Development

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    The RAS/MAPK signal transduction pathway is an intracellular signaling cascade that transmits environmental signals from activated receptor tyrosine kinases (RTKs) on the cell surface and other endomembranes to transcription factors in the nucleus, thereby linking extracellular stimuli to changes in gene expression. Largely as a consequence of its role in oncogenesis, RAS signaling has been the subject of intense research efforts for many years. More recently, it has been shown that milder perturbations in Ras signaling during embryogenesis also contribute to the etiology of a group of human diseases. Here we report the identification and characterization of the first gain-of-function germline mutation in Drosophila ras1 (ras85D), the Drosophila homolog of human K-ras, N-ras and H-ras. A single amino acid substitution (R68Q) in the highly conserved switch II region of Ras causes a defective protein with reduced intrinsic GTPase activity, but with normal sensitivity to GAP stimulation. The ras1R68Q mutant is homozygous viable but causes various developmental defects associated with elevated Ras signaling, including cell fate changes and ectopic survival of cells in the nervous system. These biochemical and functional properties are reminiscent of germline Ras mutants found in patients afflicted with Noonan, Costello or cardio-facio-cutaneous syndromes. Finally, we used ras1R68Q to identify novel genes that interact with Ras and suppress cell death

    Signaling Mechanisms of Vav3, a Guanine Nucleotide Exchange Factor and Androgen Receptor Coactivator, in Physiology and Prostate Cancer Progression

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    The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vavfamily of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPaseactivity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration-­resistant disease, Vav3 is a versatile enhancer of androgen receptor by both ligand-dependent and ligand-independent mechanisms and as such impacts established pathways of androgen receptor reactivation in advanced prostate cancer. Distinct Vav3 domains and mechanisms participate in ligand-dependent and -independent androgen receptor coactivation. To provide a physiologic context, we review Vav3 actions elucidated by gene knockout studies. This chapter describes the pervasive role of Vav3 in progression of prostate cancer to castration resistance. We discuss the mechanisms by which prostate cancer cells exploit Vav3 signaling to promote androgen receptor activity under different hormonal milieus, which are relevant to clinical prostate cancer. Lastly, we review the data on the emerging role for Vav3 in other cancers ranging from leukemias to gliomas.https://nsuworks.nova.edu/hpd_medsci_faculty_books/1002/thumbnail.jp

    Lysophosphatidic acid and sphingosine-1-phosphate promote morphogenesis and block invasion of prostate cancer cells in three-dimensional organotypic models

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    Normal prostate and some malignant prostate cancer (PrCa) cell lines undergo acinar differentiation and form spheroids in three-dimensional (3-D) organotypic culture. Acini formed by PC-3 and PC-3M, less pronounced also in other PrCa cell lines, spontaneously undergo an invasive switch, leading to the disintegration of epithelial structures and the basal lamina, and formation of invadopodia. This demonstrates the highly dynamic nature of epithelial plasticity, balancing epithelial-to-mesenchymal transition against metastable acinar differentiation. This study assessed the role of lipid metabolites on epithelial maturation. PC-3 cells completely failed to form acinar structures in delipidated serum. Adding back lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) rescued acinar morphogenesis and repressed invasion effectively. Blocking LPA receptor 1 (LPAR1) functions by siRNA (small interference RNA) or the specific LPAR1 inhibitor Ki16425 promoted invasion, while silencing of other G-protein-coupled receptors responsive to LPA or S1P mainly caused growth arrest or had no effects. The G-proteins Gα12/13 and Gαi were identified as key mediators of LPA signalling via stimulation of RhoA and Rho kinases ROCK1 and 2, activating Rac1, while inhibition of adenylate cyclase and accumulation of cAMP may be secondary. Interfering with these pathways specifically impeded epithelial polarization in transformed cells. In contrast, blocking the same pathways in non-transformed, normal cells promoted differentiation. We conclude that LPA and LPAR1 effectively promote epithelial maturation and block invasion of PrCa cells in 3-D culture. The analysis of clinical transcriptome data confirmed reduced expression of LPAR1 in a subset of PrCa's. Our study demonstrates a metastasis-suppressor function for LPAR1 and Gα12/13 signalling, regulating cell motility and invasion versus epithelial maturation

    Twitter permeability to financial events: an experiment towards a model for sensing irregularities

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    There is a general consensus of the good sensing and novelty character- istics of Twitter as an information media for the complex fi nancial market. This paper investigates the permeability of Twitter sphere, the total universe of Twitter users and their habits, towards relevant events in the financial market. Analysis shows that a general purpose social media is permeable to fi nancial-specifi c events and establishes Twitter as a relevant feeder for taking decisions regarding the fi nancial market and event fraudulent activities in that market. However, the provenance of contributions, their diferent levels of credibility and quality and even the purpose or intention behind them should to be considered and carefully contemplated if Twitter is used as a single source for decision taking. With the overall aim of this research, to deploy an architecture for real-time monitoring of irregularities in the financial market, this paper conducts a series of experiments on the level of permeability and the permeable features of Twitter in the event of one of these irregularities. To be precise, Twitter data is collected concerning an event comprising of a specifi c financial action on the 27th January 2017: the announcement about the merge of two companies Tesco PLC and Booker Group PLC, listed in the main market of the London Stock Exchange (LSE), to create the UK's Leading Food Business. The experiment attempts to answer two research questions which aim to characterize the features of Twitter permeability to the fi nancial market. The experimental results con rm that a far-impacting financial event, such as the merger considered, caused apparent disturbances in all the features considered, that is, information volume, content and sentiment as well as geographical provenance. Analysis shows that despite, Twitter not being a specifi c fi nancial forum, it is permeable to financial events

    Migrants’ decision-process shaping work destination choice: the case of long-term care work in the United Kingdom and Norway

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    Escalating demands for formal long-term care (LTC) result in the reliance on migrant workers in many developed countries. Within Europe, this is currently framed by progressive European immigration policies favouring inter-European mobility. Using the UK and Norway as case studies, this article has two main aims: (1) to document changes in the contribution of European Union (EU) migrants to the LTC sectors in Western Europe, and (2) to gain further understanding of migrants’ decision-processes relating to destination and work choices. The UK and Norway provide examples of two European countries with different immigration histories, welfare regimes, labour market characteristics and cultural values, offering a rich comparison platform. The analysis utilizes national workforce datasets and data obtained from migrants working in the LTC sector in the UK and Norway (n = 248) and other stakeholders (n = 136). The analysis establishes a significant increase in the contribution of EU migrants (particularly from Eastern Europe) to the LTC sector in both the UK and Norway despite their different welfare regimes. The findings also highlight how migrant care workers develop rational decision-processes influenced by subjective perspectives of investments and returns within a context of wider structural migration barriers. The latter includes welfare and social care policies framing the conditions for migrants’ individual actions

    Transnational Households: Migrants and Care, at Home and Abroad

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