Experimental Study on the Transfer of Polychlorinated Biphenyls (PCBs) and Polychlorinated Dibenzo-p-dioxins and Dibenzofurans (PCDD/Fs) into Milk of High-Yielding Cows during Negative and Positive Energy Balance.

Dioxin-like polychlorinated biphenyls (dl-PCBs) as well as polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are a major concern for food safety, especially in fat-containing foods of animal origin, such as milk. Due to the lipophilic character of PCDD/Fs and PCBs, it is of special interest to explore whether the metabolic state of high-yielding cows influences the transfer rates into milk. Five German Holstein cows were orally exposed to a mixture of 17 PCDD/Fs, 12 dl-PCBs, and 6 non-dioxin-like PCBs (ndl-PCBs) for two dosing periods of 28 days each. The first period covered the negative energy balance (NEB) after calving, while the second period addressed the positive energy balance (PEB) in late lactation. Each dosing period was followed by a depuration period of around 100 days. During the NEB phase, the transfer rates of 14 PCDD/Fs and 7 dl-PCBs quantified were significantly (p ≤ 0.1) higher compared to the PEB phase, indicating an influence of the metabolic state on the transfer. Furthermore, the congener-specific transfer rates (0.3-39%) were in the range of the results from former studies. This indicates that the milk yield of the exposed cows is not the only determining factor for the transfer of these congeners into milk.

Survey data of public awareness on climate change and the value of marine and coastal ecosystems.

The long-term provision of ocean ecosystem services depends on healthy ecosystems and effective sustainable management. Understanding public opinion about marine and coastal ecosystems is important to guide decision-making and inform specific actions. However, available data on public perceptions on the interlinked effects of climate change, human impacts and the value and management of marine and coastal ecosystems are rare. This dataset presents raw data from an online, self-administered, public awareness survey conducted between November 2021 and February 2022 which yielded 709 responses from 42 countries. The survey was released in four languages (English, French, Spanish and Italian) and consisted of four main parts: (1) perceptions about climate change; (2) perceptions about the value of, and threats to, coasts, oceans and their wildlife, (3) perceptions about climate change response; and (4) socio-demographic information. Participation in the survey was voluntary and all respondents provided informed consent after reading a participant information form at the beginning of the survey. Responses were anonymous unless respondents chose to provide contact information. All identifying information has been removed from the dataset. The dataset can be used to conduct quantitative analyses, especially in the area of public perceptions of the interlinkages between climate change, human impacts and options for sustainable management in the context of marine and coastal ecosystems. The dataset is provided with this article, including a copy of the survey and participant information forms in all four languages, data and the corresponding codebook.

Evaluating the combined effect of climate and anthropogenic stressors on marine coastal ecosystems: Insights from a systematic review of cumulative impact assessment approaches.

Cumulative impacts increasingly threaten marine and coastal ecosystems. To address this issue, the research community has invested efforts on designing and testing different methodological approaches and tools that apply cumulative impact appraisal schemes for a sound evaluation of the complex interactions and dynamics among multiple pressures affecting marine and coastal ecosystems. Through an iterative scientometric and systematic literature review, this paper provides the state of the art of cumulative impact assessment approaches and applications. It gives a specific attention to cutting-edge approaches that explore and model inter-relations among climatic and anthropogenic pressures, vulnerability and resilience of marine and coastal ecosystems to these pressures, and the resulting changes in ecosystem services flow. Despite recent advances in computer sciences and the rising availability of big data for environmental monitoring and management, this literature review evidenced that the implementation of advanced complex system methods for cumulative risk assessment remains limited. Moreover, experts have only recently started integrating ecosystem services flow into cumulative impact appraisal frameworks, but more as a general assessment endpoint within the overall evaluation process (e.g. changes in the bundle of ecosystem services against cumulative impacts). The review also highlights a lack of integrated approaches and complex tools able to frame, explain, and model spatio-temporal dynamics of marine and coastal ecosystems' response to multiple pressures, as required under relevant EU legislation (e.g., Water Framework and Marine Strategy Framework Directives). Progress in understanding cumulative impacts, exploiting the functionalities of more sophisticated machine learning-based approaches (e.g., big data integration), will support decision-makers in the achievement of environmental and sustainability objectives.

Transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) from oral exposure into cow's milk - Part I: state of knowledge and uncertainties.

Polychlorinated dibenzo-para-dioxins (PCDDs) and dibenzofurans (PCDFs) (collectively and colloquially referred to as 'dioxins') as well as polychlorinated biphenyls (PCBs) are persistent and ubiquitous environmental contaminants that may unintentionally enter and accumulate along the food chain. Owing to their chronic toxic effects in humans and bioaccumulative properties, their presence in feed and food requires particular attention. One important exposure pathway for consumers is consumption of milk and dairy products. Their transfer from feed to milk has been studied for the past 50 years to quantify the uptake and elimination kinetics. We extracted transfer parameters (transfer rate, transfer factor, biotransfer factor and elimination half-lives) in a machine-readable format from seventy-six primary and twenty-nine secondary literature items. Kinetic data for some toxicologically relevant dioxin congeners and the elimination half-lives of dioxin-like PCBs are still not available. A well-defined selection of transfer parameters from literature was statistically analysed and shown to display high variability. To understand this variability, we discuss the data with an emphasis on influencing factors, such as experimental conditions, cow performance parameters and metabolic state. While no universal interpretation could be derived, a tendency for increased transfer into milk is apparently connected to an increase in milk yield and milk fat yield as well as during times of body fat mobilisation, for example during the negative energy balance after calving. Over the past decades, milk yield has increased to over 40 kg/d during high lactation, so more research is needed on how this impacts feed to food transfer for PCDD/Fs and PCBs.

Transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) from oral exposure into cow's milk - part II: toxicokinetic predictive models for risk assessment.

Understanding the transfer of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) as well as polychlorinated biphenyls (PCBs) from oral exposure into cow's milk is not purely an experimental endeavour, as it has produced a large corpus of theoretical work. This work consists of a variety of predictive toxicokinetic models in the realms of health and environmental risk assessment and risk management. Their purpose is to provide mathematical predictive tools to organise and integrate knowledge on the absorption, distribution, metabolism and excretion processes. Toxicokinetic models are based on more than 50 years of transfer studies summarised in part I of this review series. Here in part II, several of these models are described and systematically classified with a focus on their applicability to risk analysis as well as their limitations. This part of the review highlights the opportunities and challenges along the way towards accurate, congener-specific predictive models applicable to changing animal breeds and husbandry conditions.

How the loss of forest fauna undermines the achievement of the SDGs.

The human-driven loss of biodiversity has numerous ecological, social, and economic impacts at the local and global levels, threatening important ecological functions and jeopardizing human well-being. In this perspective, we present an overview of how tropical defaunation-defined as the disappearance of fauna as a result of anthropogenic drivers such as hunting and habitat alteration in tropical forest ecosystems-is interlinked with four selected Sustainable Development Goals (SDGs). We discuss tropical defaunation related to nutrition and zero hunger (SDG 2), good health and well-being (SDG 3), climate action (SDG 13), and life on land (SDG 15). We propose a range of options on how to study defaunation in future research and how to address the ongoing tropical defaunation crisis, including but not limited to recent insights from policy, conservation management, and development practice.

In the blind-spot of governance - Stakeholder perceptions on seagrasses to guide the management of an important ecosystem services provider.

Seagrass ecosystems have been identified as important marine ecosystem service (ES) providers, they contribute to coastal protection, fisheries provision and mitigate climate change among others. Yet, they are declining globally at alarming rates. While the ecological dimensions of this social-ecological system have been well studied, its associated social aspects remain largely unexplored. Here, we show how the analysis of stakeholders' perceptions on seagrass ES, their drivers of change, links to wellbeing and governance structures can provide a path towards a more sustainable management. Stakeholders identified seagrass regulatory ES as crucial for the maintenance of social and economic wellbeing and the potential causes and consequences associated to seagrass decline. Power imbalances, an over-compartmentalized legislation and a generalized lack of awareness were highlighted as key aspects to redress in order to achieve a more just governance system. Stakeholders' empirical evidence on the importance of particular ES and on negative drivers of change can also provide an understanding of areas where financial investment would gather wider public support and therefore be more successfully implemented. We showed how the different dimensions highlighted through stakeholders' perspectives can contribute to the consecution of a more inclusive sustainable management, a crucial aspect in the maintenance of seagrass ecosystems.

Fishing in acid waters: A vulnerability assessment of the Norwegian fishing industry in the face of increasing ocean acidification.

Ocean acidification (OA) describes a change in the ocean's carbonate chemistry. Whereas its chemical processes are largely understood, the biological and socioeconomic consequences particularly in relation to fisheries are less known. Norway is a major fishing nation worldwide and is potentially affected by OA. To improve the understanding of the socioeconomic consequences of OA, we conducted a risk assessment among the Norwegian counties using a modified version of a risk assessment framework introduced in the Intergovernmental Panel on Climate Change's "Special Report: Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation," which considers risk to be the sum of hazard, exposure, and vulnerability. Our results show that about 13 of 19 counties are likely to experience moderate to high risk from OA. We highlight that the success of integrated risk assessments highly depends on the availability of detailed environmental, economic, and societal data. In the case of Norway, modeling data regarding the progress of OA, improved information on potential biological impacts on a larger number of species, and statistical data on social variables are required. We conclude that although still in its infancy, integrated risk assessments are important prerequisites for any form of interdisciplinary research on OA and the development of successful response strategies. Integr Environ Assess Manag 2017;13:778-789. ©2016 SETAC.

CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10-Producing Regulatory T Cells.

Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We studied the role of CD103+ DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103+ DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3-/- mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs caused cocultured T cells to differentiate into Tregs and produced the chemokine CCL20, which is known to attract Tregs into the kidney. Our findings show that CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality might be advantageous in cGN.

CX3CR1 reduces kidney fibrosis by inhibiting local proliferation of profibrotic macrophages.

A dense network of macrophages and dendritic cells (DC) expressing the chemokine receptor CX3CR1 populates most tissues. We recently reported that CX3CR1 regulates the abundance of CD11c(+) DC in the kidney and thereby promotes renal inflammation in glomerulonephritis. Given that chronic inflammation usually causes fibrosis, we hypothesized that CX3CR1 deficiency should attenuate renal fibrosis. However, when we tested this hypothesis using the DC-independent murine fibrosis model of unilateral ureteral obstruction, kidney fibrosis was unexpectedly more severe, despite less intrarenal inflammation. Two-photon imaging and flow cytometry revealed in kidneys of CX3CR1-deficient mice more motile Ly6C/Gr-1(+) macrophages. Flow cytometry verified that renal macrophages were more abundant in the absence of CX3CR1 and produced more of the key profibrotic mediator, TGF-ß. Macrophages accumulated because of higher intrarenal proliferation, despite reduced monocyte recruitment and higher signs of apoptosis within the kidney. These findings support the theory that tissue macrophage numbers are regulated through local proliferation and identify CX3CR1 as a regulator of such proliferation. Thus, CX3CR1 inhibition should be avoided in DC-independent inflammatory diseases because it may promote fibrosis.

VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF). Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source of VEGF in laser-induced choroidal neovascularization but suggest that the therapeutic efficacy of CCR2-inhibition might be limited.

Exclusive CX3CR1 dependence of kidney DCs impacts glomerulonephritis progression.

DCs and macrophages both express the chemokine receptor CX3CR1. Here we demonstrate that its ligand, CX3CL1, is highly expressed in the murine kidney and intestine. CX3CR1 deficiency markedly reduced DC numbers in the healthy and inflamed kidney cortex, and to a lesser degree in the kidney medulla and intestine, but not in other organs. CX3CR1 also promoted influx of DC precursors in crescentic glomerulonephritis, a DC-dependent aggressive type of nephritis. Disease severity was strongly attenuated in CX3CR1-deficient mice. Primarily CX3CR1-dependent DCs in the kidney cortex processed antigen for the intrarenal stimulation of T helper cells, a function important for glomerulonephritis progression. In contrast, medullary DCs played a specialized role in inducing innate immunity against bacterial pyelonephritis by recruiting neutrophils through rapid chemokine production. CX3CR1 deficiency had little effect on the immune defense against pyelonephritis, as medullary DCs were less CX3CR1 dependent than cortical DCs and because recruited neutrophils produced chemokines to compensate for the DC paucity. These findings demonstrate that cortical and medullary DCs play specialized roles in their respective kidney compartments. We identify CX3CR1 as a potential therapeutic target in glomerulonephritis that may involve fewer adverse side effects, such as impaired anti-infectious defense or compromised DC functions in other organs.