Effects of gemcitabine on APE/ref-1 endonuclease activity in pancreatic cancer cells, and the therapeutic potential of antisense oligonucleotides

Apurinic/apyrimidinic endonuclease (APE) is a key enzyme involved in DNA base excision repair (BER) that is often expressed at elevated levels in human cancers. Pancreatic cancer cells treated with the nucleoside analogue gemcitabine (2′, 2′-difluoro-2′deoxycytidine) showed increases in APE/redox effector factor (ref-1) protein levels (approximately two-fold for Panc-1 and six-fold for MiaPaCa-2), with corresponding increases in endonuclease activity. These results suggested that the activation of APE/ref-1 might be an adaptive response that contributes to gemcitabine resistance by facilitating BER. To test this hypothesis, we examined the effects of disrupting APE/ref-1 using antisense on gemcitabine toxicity. Antisense oligonucleotides decreased protein levels three-fold in MiaPaCa-2 and five-fold in Panc-1 in comparison to controls, associated with reduced endonuclease activity. Combination treatments with antisense oligonucleotides and gemcitabine partially suppressed the increase in APE/ref-1 activity seen in cells exposed to gemcitabine alone. While clonogenic assays showed only slight decreases in colony formation in cells treated with either antisense oligonucleotides or gemcitabine alone, the combination with APE/ref-1 antisense resulted in a 2-log enhancement of gemcitabine toxicity in Panc-1 cells. Overall these findings suggest that APE/ref-1 plays a significant role in gemcitabine resistance in some pancreatic cancer cells, and support the further investigation of novel treatments that target this protein

Accelerating ocean species discovery and laying the foundations for the future of marine biodiversity research and monitoring

This is the final version. Available from Frontiers Media via the DOI in this record. Ocean Census is a new Large-Scale Strategic Science Mission aimed at accelerating the discovery and description of marine species. This mission addresses the knowledge gap of the diversity and distribution of marine life whereby of an estimated 1 million to 2 million species of marine life between 75% to 90% remain undescribed to date. Without improved knowledge of marine biodiversity, tackling the decline and eventual extinction of many marine species will not be possible. The marine biota has evolved over 4 billion years and includes many branches of the tree of life that do not exist on land or in freshwater. Understanding what is in the ocean and where it lives is fundamental science, which is required to understand how the ocean works, the direct and indirect benefits it provides to society and how human impacts can be reduced and managed to ensure marine ecosystems remain healthy. We describe a strategy to accelerate the rate of ocean species discovery by: 1) employing consistent standards for digitisation of species data to broaden access to biodiversity knowledge and enabling cybertaxonomy; 2) establishing new working practices and adopting advanced technologies to accelerate taxonomy; 3) building the capacity of stakeholders to undertake taxonomic and biodiversity research and capacity development, especially targeted at low- and middle-income countries (LMICs) so they can better assess and manage life in their waters and contribute to global biodiversity knowledge; and 4) increasing observational coverage on dedicated expeditions. Ocean Census, is conceived as a global open network of scientists anchored by Biodiversity Centres in developed countries and LMICs. Through a collaborative approach, including co-production of science with LMICs, and by working with funding partners, Ocean Census will focus and grow current efforts to discover ocean life globally, and permanently transform our ability to document, describe and safeguard marine species.Nippon Foundatio

Potential impacts of climate-related decline of seafood harvest on nutritional status of coastal First Nations in British Columbia, Canada.

BACKGROUND:Traditional food systems are under pressure from various stressors, including climate change which is projected to negatively alter the abundance of marine species harvested by coastal First Nations (FNs) in British Columbia (BC). OBJECTIVE:To model the potential impacts of the climate-related declines in seafood production on the nutritional status of coastal BC FNs. In addition, we projected potential changes in nutrient intakes, under different scenarios of substitution where traditional seafood is replaced with alternative non-traditional foods. METHODS:The study design is a mixed-method approach that combines two datasets: projected scenarios of climate-related change on seafood catch potential for coastal BC FNs and data derived from the cross-sectional First Nations Food, Nutrition, and Environment Study. The consumption of seafood was estimated using a food frequency questionnaire among 356 FNs. The contribution of seafood consumption to protein, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamins (A, B12, D, niacin), and minerals (zinc, selenium and iron) requirements was assessed using Dietary Reference Intakes (DRIs). RESULTS:Traditional seafood consumption provided daily recommendations of EPA+DHA (74-184%) and vitamin B12 (84-152%) and substantial levels of niacin (28-55%), selenium (29-55%), vitamin D (15-30%) and protein (14-30%). Projected climate change was estimated to reduce the intakes of essential nutrients by 21% and 31% under 'strong mitigation' (Representative Concentration Pathway, RCP2.6) and 'business-as-usual' (RCP8.5) climate change scenarios, respectively, by the year 2050 relative to 2000. The hypothetical substitution of seafood with selected alternative non-traditional foods does not provide adequate amounts of nutrients. CONCLUSION:Traditionally-harvested seafood remains fundamental to the contemporary diet and health of coastal BC FNs. Potential dietary shifts aggravated by climate-related declines in seafood consumption may have significant nutritional and health implications for BC FN. Strategies to improve access to seafood harvest potential in coastal communities are needed to ensure nutritional health and overall well-being and to promote food security and food sovereignty in coastal FNs

Marine heatwaves exacerbate climate change impacts for fisheries in the northeast Pacific

Marine heatwaves (MHWs) have occurred in all ocean basins with severe negative impacts on coastal and ocean ecosystems. The northeast Pacific 2013–2015 MHW in particular received major societal concerns. Yet, our knowledge about how MHWs impact fish stocks is limited. Here, we combine outputs from a large ensemble simulation of an Earth system model with a fish impact model to simulate responses of major northeast Pacific fish stocks to MHWs. We show that MHWs cause biomass decrease and shifts in biogeography of fish stocks that are at least four times faster and bigger in magnitude than the effects of decadal-scale mean changes throughout the 21st century. With MHWs, we project a doubling of impact levels by 2050 amongst the most important fisheries species over previous assessments that focus only on long-term climate change. Our results underscore the additional challenges from MHWs for fisheries and their management under climate change

Toward a coordinated global observing system for seagrasses and marine macroalgae

In coastal waters around the world, the dominant primary producers are benthic macrophytes, including seagrasses and macroalgae, that provide habitat structure and food for diverse and abundant biological communities and drive ecosystem processes. Seagrass meadows and macroalgal forests play key roles for coastal societies, contributing to fishery yields, storm protection, biogeochemical cycling and storage, and important cultural values. These socio-economically valuable services are threatened worldwide by human activities, with substantial areas of seagrass and macroalgal forests lost over the last half-century. Tracking the status and trends in marine macrophyte cover and quality is an emerging priority for ocean and coastal management, but doing so has been challenged by limited coordination across the numerous efforts to monitor macrophytes, which vary widely in goals, methodologies, scales, capacity, governance approaches, and data availability. Here, we present a consensus assessment and recommendations on the current state of and opportunities for advancing global marine macrophyte observations, integrating contributions from a community of researchers with broad geographic and disciplinary expertise. With the increasing scale of human impacts, the time is ripe to harmonize marine macrophyte observations by building on existing networks and identifying a core set of common metrics and approaches in sampling design, field measurements, governance, capacity building, and data management. We recommend a tiered observation system, with improvement of remote sensing and remote underwater imaging to expand capacity to capture broad-scale extent at intervals of several years, coordinated with stratified in situ sampling annually to characterize the key variables of cover and taxonomic or functional group composition, and to provide ground-truth. A robust networked system of macrophyte observations will be facilitated by establishing best practices, including standard protocols, documentation, and sharing of resources at all stages of workflow, and secure archiving of open-access data. Because such a network is necessarily distributed, sustaining it depends on close engagement of local stakeholders and focusing on building and long-term maintenance of local capacity, particularly in the developing world. Realizing these recommendations will produce more effective, efficient, and responsive observing, a more accurate global picture of change in vegetated coastal systems, and stronger international capacity for sustaining observations

Establishing the Foundation for the Global Observing System for Marine Life

Maintaining healthy, productive ecosystems in the face of pervasive and accelerating human impacts including climate change requires globally coordinated and sustained observations of marine biodiversity. Global coordination is predicated on an understanding of the scope and capacity of existing monitoring programs, and the extent to which they use standardized, interoperable practices for data management. Global coordination also requires identification of gaps in spatial and ecosystem coverage, and how these gaps correspond to management priorities and information needs. We undertook such an assessment by conducting an audit and gap analysis from global databases and structured surveys of experts. Of 371 survey respondents, 203 active, long-term (>5 years) observing programs systematically sampled marine life. These programs spanned about 7% of the ocean surface area, mostly concentrated in coastal regions of the United States, Canada, Europe, and Australia. Seagrasses, mangroves, hard corals, and macroalgae were sampled in 6% of the entire global coastal zone. Two-thirds of all observing programs offered accessible data, but methods and conditions for access were highly variable. Our assessment indicates that the global observing system is largely uncoordinated which results in a failure to deliver critical information required for informed decision-making such as, status and trends, for the conservation and sustainability of marine ecosystems and provision of ecosystem services. Based on our study, we suggest four key steps that can increase the sustainability, connectivity and spatial coverage of biological Essential Ocean Variables in the global ocean: (1) sustaining existing observing programs and encouraging coordination among these; (2) continuing to strive for data strategies that follow FAIR principles (findable, accessible, interoperable, and reusable); (3) utilizing existing ocean observing platforms and enhancing support to expand observing along coasts of developing countries, in deep ocean basins, and near the poles; and (4) targeting capacity building efforts. Following these suggestions could help create a coordinated marine biodiversity observing system enabling ecological forecasting and better planning for a sustainable use of ocean resources