Seafood trade routes for lobster obscure teleconnected vulnerabilities

© 2018 Stoll, Crona, Fabinyi and Farr. Reliance on international seafood markets leaves small-scale fishers and fishing economies vulnerable to distant disturbances that can negatively affect market prices and trigger social, economic, and environmental crises at local levels. This paper examines the role of seafood trade routes and re-exports in masking such market linkages. We employ a network approach to map the global trade routes of lobster (Homarus spp.) from small-scale producers in North America to terminal markets and evaluate the extent to which intermediary nations act to obscure producer-market relationships. In taking this approach, we provide a method for systematically measuring "teleconnectivity" created through seafood trade routes, and thus making explicit vulnerabilities to small-scale fisheries from this teleconnectivity. Our empirical analysis shows that the perceived trade diversification of lobster producers is masking increased dependencies on a reduced number of end-markets, particularly in Asia. These results suggest, paradoxically, that the apparent diversification of trade partnerships may actually amplify, rather than reduce, the vulnerabilities of small-scale fishers associated with international trade by making risk harder to identify and anticipate. We discuss our results in the context of local fisheries and global seafood trade and describe key impediments to being able to monitor market dependencies and exposure to potential vulnerabilities

The Gendered Nature of Ecosystem Services

This is the final version. Available from Elsevier via the DOI in this record. This article assesses the extent to which our conceptualisation, understanding and empirical analysis of ecosystem services are inherently gendered; in other words, how they might be biased and unbalanced in terms of their appreciation of gender differences. We do this by empirically investigating how women and men are able to benefit from ecosystem services across eight communities in coastal Kenya and Mozambique. Our results highlight different dimensions of wellbeing affected by ecosystem services, and how these are valued differently by men and women. However, it is not just the division of costs and benefits of ecosystem services that is gendered. Using a heuristic device of the ‘ecosystem-wellbeing chain’ we explain patterns within our primary data as an outcome of gendered knowledge systems, gendered behavioural expectations, gendered access to resources and gendered institutions. We conclude that this holistic, gendered understanding of ecosystem services is important not just for how ecosystem services are conceptualised, but also for the development and implementation of sustainable and equitable policy and interventions.Natural Environment Research Council (NERC)Ecosystem Services for Poverty Alleviation (ESPA)Economic and Social Research Council (ESRC

Androgen receptor targeting drugs in castration-resistant prostate cancer and mechanisms of resistance

Reactivated androgen receptor (AR) signaling drives castration-resistant prostate cancer (CRPC). Novel AR targeting drugs abiraterone and enzalutamide have improved survival of CRPC patients. However, resistance to these agents develops and patients ultimately succumb to CRPC. Potential mechanisms of resistance include the following: 1) Expression of AR splice variants such as the AR-V7 isoform which lacks the ligand-binding domain, 2) AR missense mutations in the ligand-binding domain, such as F876L and T877A, and 3) Mutation or overexpression of androgen biosynthetic enzymes or glucocorticoid receptor. Several novel agents may overcome resistance mechanisms. Galeterone acts through multiple mechanisms that include degradation of AR protein and is being evaluated in CRPC patients positive for AR-V7. EPI-001 and related compounds inhibit AR splice variants by targeting the N-terminal transactivation domain of AR. Promising therapies and novel biomarkers, such as AR-V7, may lead to improved outcomes for CRPC patients

Genetic Variants of VEGFA and FLT4 Are Determinants of Survival in Renal Cell Carcinoma Patients Treated with Sorafenib

Molecular markers of sorafenib efficacy in patients with metastatic renal cell carcinoma (mRCC) are not available. The purpose of this study was to discover genetic markers of survival in patients with mRCC treated with sorafenib. Germline variants from 56 genes were genotyped in 295 patients with mRCC. Variant-overall survival (OS) associations were tested in multivariate regression models. Mechanistic studies were conducted to validate clinical associations. VEGFA rs1885657, ITGAV rs3816375, and WWOX rs8047917 (sorafenib arm), and FLT4 rs307826 and VEGFA rs3024987 (sorafenib and placebo arms combined) were associated with shorter OS. FLT4 rs307826 increased VEGFR-3 phosphorylation, membrane trafficking, and receptor activation. VEGFA rs1885657 and rs58159269 increased transcriptional activity of the constructs containing these variants in endothelial and RCC cell lines, and VEGFA rs58159269 increased endothelial cell proliferation and tube formation. FLT4 rs307826 and VEGFA rs58159269 led to reduced sorafenib cytotoxicity. Genetic variation in VEGFA and FLT4 could affect survival in sorafenib-treated patients with mRCC. These markers should be examined in additional malignancies treated with sorafenib and in other angiogenesis inhibitors used in mRCC. Significance: Clinical and mechanistic data identify germline genetic variants in VEGFA and FLT4 as markers of survival in patients with metastatic renal cell carcinoma.Peer reviewe

DNA building blocks: keeping control of manufacture

Ribonucleotide reductase (RNR) is the only source for de novo production of the four deoxyribonucleoside triphosphate (dNTP) building blocks needed for DNA synthesis and repair. It is crucial that these dNTP pools are carefully balanced, since mutation rates increase when dNTP levels are either unbalanced or elevated. RNR is the major player in this homeostasis, and with its four different substrates, four different allosteric effectors and two different effector binding sites, it has one of the most sophisticated allosteric regulations known today. In the past few years, the structures of RNRs from several bacteria, yeast and man have been determined in the presence of allosteric effectors and substrates, revealing new information about the mechanisms behind the allosteric regulation. A common theme for all studied RNRs is a flexible loop that mediates modulatory effects from the allosteric specificity site (s-site) to the catalytic site for discrimination between the four substrates. Much less is known about the allosteric activity site (a-site), which functions as an on-off switch for the enzyme's overall activity by binding ATP (activator) or dATP (inhibitor). The two nucleotides induce formation of different enzyme oligomers, and a recent structure of a dATP-inhibited α6β2 complex from yeast suggested how its subunits interacted non-productively. Interestingly, the oligomers formed and the details of their allosteric regulation differ between eukaryotes and Escherichia coli Nevertheless, these differences serve a common purpose in an essential enzyme whose allosteric regulation might date back to the era when the molecular mechanisms behind the central dogma evolved

Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer

This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer

The Gendered Nature of Ecosystem Services

This article assesses the extent to which our conceptualisation, understanding and empirical analysis of ecosystem services are inherently gendered; in other words, how they might be biased and unbalanced in terms of their appreciation of gender differences. We do this by empirically investigating how women and men are able to benefit from ecosystem services across eight communities in coastal Kenya and Mozambique. Our results highlight different dimensions of wellbeing affected by ecosystem services, and how these are valued differently by men and women. However, it is not just the division of costs and benefits of ecosystem services that is gendered. Using a heuristic device of the ‘ecosystem-wellbeing chain’, we explain patterns within our primary data as an outcome of gendered knowledge systems, gendered behavioural expectations, gendered access to resources and gendered institutions. We conclude that this holistic, gendered understanding of ecosystem services is important not just for how ecosystem services are conceptualised, but also for the development and implementation of sustainable and equitable policy and interventions

Transnational corporations and the challenge of biosphere stewardship

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordSustainability within planetary boundaries requires concerted action by individuals, governments, civil society and private actors. For the private sector, there is concern that the power exercised by transnational corporations generates, and is even central to, global environmental change. Here, we ask under which conditions transnational corporations could either hinder or promote a global shift towards sustainability. We show that a handful of transnational corporations have become a major force shaping the global intertwined system of people and planet. Transnational corporations in agriculture, forestry, seafood, cement, minerals and fossil energy cause environmental impacts and possess the ability to influence critical functions of the biosphere. We review evidence of current practices and identify six observed features of change towards 'corporate biosphere stewardship', with significant potential for upscaling. Actions by transnational corporations, if combined with effective public policies and improved governmental regulations, could substantially accelerate sustainability efforts.Beijer FoundationErling-Persson Family FoundationMarianne and Marcus Wallenberg FoundationWalton Family FoundationDavid and Lucile Packard FoundationGordon and Betty Moore FoundationMistra: The Swedish Foundation for Strategic Environmental Researc