Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy

The fatty acid transport protein family is a group of evolutionarily conserved proteins that are involved in the cellular uptake and metabolism of long and very long chain fatty acids. However, little is known about their respective physiological roles. To analyze the functional significance of fatty acid transport protein 4 (Fatp4, Slc27a4), we generated mice with a targeted disruption of the Fatp4 gene. Fatp4-null mice displayed features of a neonatally lethal restrictive dermopathy. Their skin was characterized by hyperproliferative hyperkeratosis with a disturbed epidermal barrier, a flat dermal–epidermal junction, a reduced number of pilo-sebaceous structures, and a compact dermis. The rigid skin consistency resulted in an altered body shape with facial dysmorphia, generalized joint flexion contractures, and impaired movement including suckling and breathing deficiencies. Lipid analysis demonstrated a disturbed fatty acid composition of epidermal ceramides, in particular a decrease in the C26:0 and C26:0-OH fatty acid substitutes. These findings reveal a previously unknown, essential function of Fatp4 in the formation of the epidermal barrier

ATP-binding cassette (ABC) transporters in normal and pathological lung

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases

Ecosystem Services and Soil Quality

In acknowledgement of the globally declining state of ecosystems and its services, Switzerland formulated a national strategy on sustainability, based on the United Nations Sustainable Development Goals (SDG). Two important partial goals of the Swiss Strategy on Sustainability are the sustainable use of natural resources, and the sustainable development of urban areas and their associated infrastructure. Achievement of these two goals requires, in turn, successfully addressing three important drivers of ES loss, namely economic globalization, climate change, and urbanization. The impacts and interactions of these three drivers present manifold challenges to spatial decision-making and policy, as they occur across scales and across social, economic, and ecological systems. Tools designed to mitigate their negative effects can lead to unintentional trade-offs or even to reinforcement of negative effects as previously unknown feedback effects trigger. Urbanization, in particular, having considerable spatial impacts, has a large influence on ES supply and, more specifically, on the quality of soil. Yet, soil, while elementary to human existence, is often sidelined and marginalized as a surface in spatial decision-making. As soil is highly multi-functional and provides a broad range of ES, the permanent loss of its ability to function once sealed causes significant degradation of ES supply. Successful formulation of well-informed, comprehensive strategies that aim at achieving the stated sustainability goals thus requires not only knowledge on the trade-offs and feedback effects across and between drivers, instruments, and both ecological as well as social systems. Rather, for achieving ES sustainability it is paramount to take soil and the benefits it provides actively into account in policy and spatial decision-making. The necessary information is not readily available, though. For revealing unintentional trade-offs and unknown feedback effects, models are often employed, allowing to explore the range of possible outcomes. To achieve this, a model needs to be able to simulate feedback effects in the non-linear relationships of ecological and social systems. Agent-based modelling (ABM) is particularly suitable to handle exploratory questions on the effects of new tools and instruments on coupled social-ecological systems: Whereas most modelling approaches assume perfect rationality in decision-making, a suitable ABM needs to represent individual, preference-based decision-making by incorporating the personal goals and belief systems as well as characteristic traits of actors. Consequently, such ABM can then not only simulate the results of interaction between different stakeholders, policy instruments, and the environment, but also how these results feed back into decision-making and, potentially, modify the outcome. For soil and its services, the challenge involves not only how to implement multi-functional soil quality into decision-making, but also how to effectively communicate the importance of soil quality, as these two aspects are closely related. Research on soil quality has a long-standing history, and researchers have called for better consideration of soil in spatial decision-making for decades. However, communicating the importance of soil quality outside the soil community is an equally long-standing problem, and high disciplinary specialization within the soil community is further compounding the issue. To overcome the marginalization of soil as a surface, scientists suggested to rely on the increasingly popular concept of ‘ecosystem services’ as it might help in creating a unifying and accessible link between soil multi-functionality and the benefits it offers to humans. Although considered a promising idea, linking soil and ES has seen very little use, and as of now I am unaware of any application in practice. The goal of this thesis is, thus, to advance the consideration of soil and its services in sustainable decision-making. This involves three steps: First, I apply an ABM to explore the interactions of actors, policies, and land uses on the quantitative and qualitative ES supply across scales and to investigate the emergence of unintentional trade-offs. Second, I demonstrate that the ES concept can be operationalized for soil, making soil and its services not only accessible to non-experts but also offering a way to include benefit-oriented soil quality into decision-making. Third, I take the concept of “No Net Loss”, which constitutes the goal II to achieve an overall neutral outcome of project environmental impacts by employing appropriate compensation measures, and adapt it to soil as a mean for establishing and monitoring a long-term strategy for soil quality preservation. In combination, this contributes necessary knowledge for advancing the formulation of soil sustainability strategies, providing helpful information on the spatial distribution of soil-based ES, on assessing trade-offs in ES supply across scales and systems, and on the challenges of securing soil-based ES supply in the long term. Interactions of actors, policies, and land use and their effect on ES supply are discussed in detail in Chapter 2. To explore the range of possible outcomes, I link ABM with a cellular automata driven by multi-criteria decision analysis (MCDA): The MCDA-driven cellular automata simulates settlement growth under the twin goals of minimizing ES loss as well as minimizing urban sprawl while still taking into account location factors like development cost or distance to municipal centers. ABM simulates agricultural decision-making at the level of individual farmers, taking into account climatic and socio-economic boundary conditions, personal preferences, and the effects of settlement expansion. New policies are implemented as spatial planning instruments that change the cooperation of municipalities as well as allocation rules for new settlement areas. As was expected, explicit consideration of ES in settlement expansion helps reducing loss of ES supply due to sealing. However, maximum effect can only be achieved if municipalities fully cooperate. This cooperation should include ES prioritization, as the largest improvements in ES preservation often arise from the preservation of ES supply that is locally important because of its high quality, relative scarcity within municipal boundaries, or a combination thereof. While implemented spatial planning instruments succeed in achieving the main goal of reduced ES losses, the unexpected downside is an increased pressure especially on farmers focusing on extensive, ecological farming activities as they experience increased competition with settlement expansion for marginal areas. In Chapter 3, I present the development of a new soil quality index that operationalizes the ES concept for soil quality. The SQUID (Soil QUality InDex) is based on detailed and scientifically solid soil functions, which are then linked to soil-based ES provision using an expert-based Delphi survey. Finally, soil-based ES provision is aggregated into a single index intended to provide a quick and easy-to-understand interpretation of the distribution and quality of soil ES to decision-makers. To test the capability of such an ES-based soil quality index, I selected an existing German soil quality index specifically developed for use in spatial planning and adapted it to Swiss conditions. While the adapted German soil quality index has the edge in terms of clarity, the SQUID excels in emphasizing the high spatial variability of soil quality and covers a broader range of soil ES, including soil contribution to cultural ES. Unlike most soil quality indices, the SQUID does not aim at objectivity but rather at illustrating the distribution of good soils for a variety of soil users, facilitating incorporation of stakeholder preferences and supporting discussions on soil use preferences. Chapter 4 exemplifies how the previously introduced soil quality index SQUID can provide the necessary foundation to adopt the NNL concept for soil quality. Although it cannot address all criticism leveled at the NNL concept, the SQUID can successfully address some of the main issues: By making soil quality measurable, it allows ascertaining baseline situations, assessing impacts, evaluating compensation gains, and comparison of different solutions. In addition, the capability of the SQUID to incorporate stakeholder preferences on soil ES supply allows to address differences in spatial distribution between and associated trade-offs in soil ES supply of different compensation goals. Finally, combining the SQUID with a market-based instrument for steering spatial development suggests that implementation of a soil-oriented NNL strategy could help in achieving sustainable use of soil resources, but only with careful consideration of the consequences for social equity or speculation risk – topics that have so far not been looked into. By drawing from a broad range of disciplines, this thesis demonstrates how a sustainability strategy can profit from explicit consideration of the services soil has to offer, from assessing trade-offs across scales and systems, and generally from taking ES supply into account in spatial decision-making. Although the scope of the problem – tackling the negative consequences of the three interdependent drivers, economic globalization, climate change, and urbanization – presents a considerable challenge for spatial decision- III making and policy in general, the insights and methodological advancement made in this thesis provide a first step to implement a sustainability strategy. Chapter 5 synthesizes the knowledge gathered over the course of the previous chapters and discusses the questions this thesis falls short in answering, before presenting follow-up projects and further research opportunities. With regard to unanswered questions, sustainable management of soil as a resource must be considered a wicked problem, three specific aspects need answering: Complexity, uncertainty, and normativity. The methodologies developed in this thesis and the knowledge drawn from them, however, focus on complexity. Uncertainty and normativity can be addressed by the approaches presented, but they have not been investigated in detail. Normativity, specifically, requires a well-developed approach to include and to negotiate various goals as a prerequisite to reach the full range of SDGs, i.e., social, economic, and ecologic SDGs. Normativity is, thus, also a contributing factor to uncertainty. Consequently, uncertainty cannot be answered purely by traditional methodologies designed to reduce uncertainty, like sensitivity analysis or increasing the number of involved persons or case studies. The methodologies developed in this thesis lead to the start of two follow-up projects, which are conducted in cooperation with federal institutions. The goal of these two projects is to, on one hand, develop the necessary legal framework to implement the NNL concept in Swiss spatial planning and, on the other hand, to further explore the benefits and problems of integrating the ES-based soil quality index SQUID into spatial and landscape planning. The thesis closes with a short discussion of future research possibilities, with suggestions revolving around more in-depth research on ES trade-offs and mismatches in ES supply, more comprehensive stakeholder involvement, research into aggregation schemes, and ultimately with some ideas on how to increase the amount of soil stakeholders, i.e., people that have an active interest in soils

Moving towards integrating soil into spatial planning: No net loss of soil-based ecosystem services

Degradation of ecosystems and the related loss of ecosystem services have called for new policies to achieve no net loss (NNL) of or even net gain between detrimental environmental impacts and restoration or preservation measures. While biodiversity offsetting has a long tradition, soils have rarely been considered in the accounting. Considering the crucial role of soil for ecosystem functioning and biodiversity and the increasing pressure on soil resources, we investigate how a NNL strategy building on a soil-based ecosystem services index can help steer sustainable spatial development. An ecosystem services’ soil quality index allows to explicitly address the interests of a broad range of stakeholder on soil uses. Using a market-driven spatial planning instrument based on a land price fee linked to the soil quality index, we demonstrate how soil quality loss and related ecosystem services could be reduced by up to 60% compared to current practice in a case study in Switzerland. More importantly, the suggested instrument allows to account for the spatial variability of the supply of the ecosystem services and the diversity of stakeholder demands for various soil qualities. We close with a discussion on the consequences of implementing a soil-based NNL strategy for spatial development and its generic application for steering settlement development.ISSN:0301-4797ISSN:1095-863

Soil quality indicators – From soil functions to ecosystem services

ISSN:1470-160

Coupling a settlement growth model with an agro-economic land allocation model for securing ecosystem services provision

<p>Mountain landscapes are undergoing rapid land-use changes. Settlement expansion, the intensification of agricultural land-use practices, and farmland abandonment result in a decline of natural and semi-natural habitats and the related ecosystem services (ES). In this context, spatial planning has emerged as a key instrument for the management of ES provision. To better understand trade-offs and interactions between settlement growth and ES provision in a spatially explicit manner, we present a new modeling framework coupling an agent-based, agro-economic optimization model and a cellular-automata-based settlement growth model. The framework is applied in an inner alpine valley in the Valais, Switzerland, which experienced rapid settlement growth in recent years. Results demonstrate how the model framework allows support of local planning processes. Particularly cooperation among municipalities and an explicit consideration of ES can inform spatially explicit ES trade-off decisions under increasing demand for land. We conclude that better informed spatial planning processes support ES provision.</p