Epigenetic Dysregulation in Mesenchymal Stem Cell Aging and Spontaneous Differentiation

BACKGROUND: Mesenchymal stem cells (MSCs) hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Human MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes. CONCLUSIONS/SIGNIFICANCE: Our results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation

Artisanal fish fences pose broad and unexpected threats to the tropical coastal seascape

Gear restrictions are an important management tool in small-scale tropical fisheries, improving sustainability and building resilience to climate change. Yet to identify the management challenges and complete footprint of individual gears, a broader systems approach is required that integrates ecological, economic and social sciences. Here we apply this approach to artisanal fish fences, intensively used across three oceans, to identify a previously underrecognized gear requiring urgent management attention. A longitudinal case study shows increased effort matched with large declines in catch success and corresponding reef fish abundance. We find fish fences to disrupt vital ecological connectivity, exploit > 500 species with high juvenile removal, and directly damage seagrass ecosystems with cascading impacts on connected coral reefs and mangroves. As semi-permanent structures in otherwise open-access fisheries, they create social conflict by assuming unofficial and unregulated property rights, while their unique high-investment-low-effort nature removes traditional economic and social barriers to overfishing

The EBM-DPSER conceptual model: integrating ecosystem services into the DPSIR framework

There is a pressing need to integrate biophysical and human dimensions science to better inform holistic ecosystem management supporting the transition from single species or single-sector management to multi-sector ecosystem-based management. Ecosystem-based management should focus upon ecosystem services, since they reflect societal goals, values, desires, and benefits. The inclusion of ecosystem services into holistic management strategies improves management by better capturing the diversity of positive and negative human-natural interactions and making explicit the benefits to society. To facilitate this inclusion, we propose a conceptual model that merges the broadly applied Driver, Pressure, State, Impact, and Response (DPSIR) conceptual model with ecosystem services yielding a Driver, Pressure, State, Ecosystem service, and Response (EBM-DPSER) conceptual model. The impact module in traditional DPSIR models focuses attention upon negative anthropomorphic impacts on the ecosystem; by replacing impacts with ecosystem services the EBM-DPSER model incorporates not only negative, but also positive changes in the ecosystem. Responses occur as a result of changes in ecosystem services and include inter alia management actions directed at proactively altering human population or individual behavior and infrastructure to meet societal goals. The EBM-DPSER conceptual model was applied to the Florida Keys and Dry Tortugas marine ecosystem as a case study to illustrate how it can inform management decisions. This case study captures our system-level understanding and results in a more holistic representation of ecosystem and human society interactions, thus improving our ability to identify trade-offs. The EBM-DPSER model should be a useful operational tool for implementing EBM, in that it fully integrates our knowledge of all ecosystem components while focusing management attention upon those aspects of the ecosystem most important to human society and does so within a framework already familiar to resource managers

The Impact of Offshore Wind Farms on Marine Ecosystems: A Review Taking an Ecosystem Services Perspective

The rapid increase in renewable energy generation from wind has increased concerns about the impacts that wind arrays have on the marine environment and what these impacts mean for society. One method for identifying the impacts of offshore wind farms (OWFs) on human welfare is through the assessment and valuation of ecosystem services. Using an ecosystem services approach, this paper reviews the impacts of OWFs on the ecosystem services delivered by marine environments. During the construction phase, supporting services such as reduced energy capture and nutrient cycling are changed due to the introduction of hard substrate and the reduction in soft sediment habitat at turbine bases. This may lead to changes in all other ecosystem services, both negative and positive. Quantifying these changes, however, is a challenge partly due to data limitations and a lack of clear understanding of the impacts of OWFs on the marine ecosystems. Scientific effort needs to quantitatively explore the impacts of OWFs on ecosystem functionality and the gathering of data that enables the assessment of changes to ecosystem services. Data needed to better quantify and value the impacts of OWFs on ecosystem services are suggested. The development of methods which integrate socioeconomic valuation of ecosystem services into the evaluation of renewable energy devices compliments efforts in assessing the environmental impacts and should enable a holistic assessment of the impact of renewable energy production and greenhouse gas mitigation technologies on the U. K. carbon footprint

Social impacts of a temperate fisheries closure: understanding stakeholders' views

The social dimensions of marine protected areas (MPAs) play an important role in MPA success, yet these social dimensions are little understood. We explore the social impacts arising from the establishment of an MPA using Lyme Bay (south west England) as a case study. Through a series of small group semi-structured interviews the social impacts experienced by fishermen (mobile and static gear), recreational users (divers and sea anglers) and recreation service providers (charter boat and dive businesses) were explored. The social impacts expressed varied according to activity in which the stakeholder group engaged. Negative themes included lengthening fishing trips, tension and conflict, fishermen identity, equity and uncertainty in the long-term. Positive themes included improved experiences for both commercial fishermen and recreational users, and expectations for long-term benefits. These impacts need to be understood because they influence stakeholder behaviour. Failure to interpret stakeholder responses may lead to poor decision-making and worsening stakeholder relations. These findings have implications for the success of the MPA in Lyme Bay, but also for the future network of marine conservation zones around the UK. Any assessment of MPA impacts must therefore identify social as well as economic and environmental change