Hsc70-4 Deforms Membranes to Promote Synaptic Protein Turnover by Endosomal Microautophagy

SummarySynapses are often far from their cell bodies and must largely independently cope with dysfunctional proteins resulting from synaptic activity and stress. To identify membrane-associated machines that can engulf synaptic targets destined for degradation, we performed a large-scale in vitro liposome-based screen followed by functional studies. We identified a presynaptically enriched chaperone Hsc70-4 that bends membranes based on its ability to oligomerize. This activity promotes endosomal microautophagy and the turnover of specific synaptic proteins. Loss of microautophagy slows down neurotransmission while gain of microautophagy increases neurotransmission. Interestingly, Sgt, a cochaperone of Hsc70-4, is able to switch the activity of Hsc70-4 from synaptic endosomal microautophagy toward chaperone activity. Hence, Hsc70-4 controls rejuvenation of the synaptic protein pool in a dual way: either by refolding proteins together with Sgt, or by targeting them for degradation by facilitating endosomal microautophagy based on its membrane deforming activity

An assessment of dedicated energy crops in Europe under the EU Energy Reference Scenario 2013. Application of the LUISA modelling platform - Updated Configuration 2014

This report presents a comprehensive analysis of dedicated energy crops (ENCR) performed with the LUISA (Land Use-based Integrated Sustainability Assessment) modelling platform across Europe between 2020 and 2050. LUISA is configured in compliance with the “EU Energy, Transport and GHG emissions trends until 2050” document in order to ensure that the EU meet its climate and energy targets up to 2050 (EU Reference Scenario 2013, updated LUISA configuration 2014). The spatial modelling of ENCR in LUISA requires determining a set of elements such as the land demand, availability and suitability of the land, and other land categories for the ENCR cultivation. Thus, the assessment is focused on the following steps: 1) Land accounts and dominant land use/cover flows for the expansion of energy crops at European scale, 2) A suitability analysis of the land dedicated to these crops based on suitability maps, 3) Recuperation of degraded and contaminated lands for energy purpose, 4) A detailed regional analysis per each Member State (factsheets) with a summary of the main important findings, and 5) Evaluation of energy crops’ impacts on a selection of environmental indicators (provision of ecosystem services). In LUISA, the displacement and cultivation of crops solely dedicated to energy production takes place on a specific land-use class named ‘energy crop’ (ENCR), which competes in particular with the demand for others land-uses, such as for food, feed and forest. The amount of ENCR reaches about 13,549 kha in 2050 that represents, on average, 3.6% of Europe’s total available land. This expansion occurs mainly at expenses of land for food and feed (90%). Forest and natural land (9% and 1%,) represent respectively the second and third land flows towards ENCR among total land-use changes (with these flows represented respectively 9 and 1% of all land use changes). As result of this land competition, there is an increasing shift of food and feed crops towards low quality land, due not only to the ENCR expansion but also to the growth of residential and economic-driven land uses. It should also be noted that intensive agriculture practices for ENCR production might have some negative impacts on soil, water, biodiversity, amongst others. Owing to this potential impacts, the analysis performed on the supply of a set of ecosystem services identifies some services more sensitive than others to ENCR growth. In particular, pollination potential, habitat quality for birds and also the Green-Infrastructure network are expected to decrease due to ENCR growth, while patterns for recreational opportunities and water retention services are less evident.JRC.H.8-Sustainability Assessmen

Direct and Indirect Land Use Impacts of the EU Cohesion Policy. Assessment with the Land Use Modelling Platform

The Cohesion policy for the programming period 2014-2020 is analyzed in terms of its likely land use and environmental impacts using the Land Use Modelling Platform (LUMP). This report describes in detail the process and the methodology by which the ex-ante impact assessment was made, and presents the results for Austria, Czech Republic, Germany, and Poland. The modelling approach can provide insights on the trade-offs between economic growth, investment policies (such as the Cohesion policy), and land use and the environment. In addition, ways to mitigate potentially negative land use and environmental impacts were explored. The future development of the LUMP is discussed in view of planned future work.JRC.H.8-Sustainability Assessmen

More green infrastructure is required to maintain ecosystem services under current trends in land-use change in Europe

Green infrastructure (GI), a network of nature, semi-natural areas and green space, delivers essential ecosystem services which underpin human well-being and quality of life. Maintaining ecosystem services through the development of GI is therefore increasingly recognized by policies as a strategy to cope with potentially changing conditions in the future. This paper assessed how current trends of land-use change have an impact on the aggregated provision of eight ecosystem services at the regional scale of the European Union, measured by the Total Ecosystem Services Index (TESI8). Moreover, the paper reports how further implementation of GI across Europe can help maintain ecosystem services at baseline levels. Current demographic, economic and agricultural trends, which affect land use, were derived from the so called Reference Scenario. This scenario is established by the European Commission to assess the impact of energy and climate policy up to 2050. Under the Reference Scenario, economic growth, coupled with the total population, stimulates increasing urban and industrial expansion. TESI8 is expected to decrease across Europe between 0 and 5 % by 2020 and between 10 and 15 % by 2050 relative to the base year 2010. Based on regression analysis, we estimated that every additional percent increase of the proportion of artificial land needs to be compensated with an increase of 2.2 % of land that qualifies as green infrastructure in order to maintain ecosystem services at 2010 levels.JRC.H.8-Sustainability Assessmen

European cities: territorial analysis of characteristics and trends - An application of the LUISA Modelling Platform (EU Reference Scenario 2013 - Updated Configuration 2014)

Cities and towns are at the core of the European economy but they are often also the places where problems related to the quality of life of citizens such as unemployment, segregation and poverty are most evident. To curtail the negative impacts and foster the positive effects of ongoing urban processes in Europe, policies have to be adjusted and harmonised to accommodate future urbanization trends. Such an analysis of the evolution of European cities requires the evaluation of impacts of continent-wide drivers and, at the same time, assessment of the effect of national and local strategies. As a contribution to this analysis of the current and future evolution of European territories (countries, macro-regions, regions or urban areas), the Directorate-General Joint Research Centre (DG JRC) of the European Commission (EC) has developed the Land-Use-based Integrated Sustainability Assessment (LUISA) Modelling Platform. Based on the concept of ‘dynamic land functions’, LUISA has adopted a novel approach towards activity-based modelling and endogenous dynamic allocation of population, services and activities. This report illustrates how European cities could potentially evolve over the time period 2010-2050, according to the reference configuration of the LUISA modelling platform, on the basis of a collection of spatial indicators covering several thematic fields. These spatial indicators aim to improve our understanding of urbanization and urban development processes in Europe; explore territorial dimensions of projected demographic and economic changes, and finally examine some key challenges that urban areas are or may be exposed to. Some of the key findings of this report are given below: - The proportion of the population living in cities, towns and suburbs is higher in the EU than in the rest of the world. According to the LUISA forecasts, the urban proportion will continue to increase up to 2030; subsequently slow down, and reach a relatively steady state by 2050. - In 2010, 65% of the EU population were living in Functional Urban Areas (FUA, the city and its commuting zone). This figure is expected to reach 70% by 2050. The total EU-28 population is expected to grow by 4.6%. Most of this population growth will occur particularly in FUA which will grow by an average 14%. - As of 2010, the amount of artificial areas per inhabitant in the EU-28 was estimated as 498 m2: it becomes 539 m2 in 2050 with an 8% increase. Although there is not a unique spatial pattern, land take tends to start peak at 5 km distance from the city centre. This is due to the fact that land is often less available for development within city centres and that the majority of land take therefore will occur firstly in the suburbs and then in rural areas. - By 2050, potential accessibility – as measure of economic opportunities - will be higher in the urban areas of north-western Europe, while it will not improve in lagging European regions. Urban form has a considerable impact on average travelled distances and thus potentially on the energy dependence of transport. - Green infrastructure is mainly located at the periphery of urban areas. Its share per person is generally low or very low in most of the European cities, with few exceptions. Green infrastructure per capita in FUA shows a general trend towards a decrease across the EU-28 (by approximately 13%) between 2010 and 2050. - Larger cities tend to have higher average flood risk, especially due to the higher sensitivity in terms of potential human and physical losses. The analysis herein presented is part of a wider initiative of DG JRC and DG REGIO aiming to improve the management of knowledge and sharing of information related to territorial policies, such as those concerning urban development. In this framework, the work will be further developed, covering the following main elements: - Development of the European Urban Data Platform, providing a single access point for data and indicators on the status and trends of European urban areas; - Updates of the LUISA configuration, to account for new socio-economic projections; - Support to the development of the EU Urban Agenda and related initiatives; - Provision of evidence-based support for the evaluation of territorial policies in particular to proof the role of cities in the implementation of EU priorities.JRC.H.8-Sustainability Assessmen

LUISA Dynamic Land Functions: Catalogue of Indicators – Release I: EU Reference Scenario 2013 LUISA Platform - Updated Configuration 2014

The concept of ‘dynamic land function’ is a new notion for cross-sector integration and for the representation of complex system dynamics. A land function can be societal (e.g. provision of housing, leisure and recreation), economic (e.g. provision of production factors - employment, investments, energy – or provision of manufacturing products and services – food, fuels, consumer goods, etc.) or environmental (e.g. supply of ecosystem services). Land functions are temporally and spatially dynamic, and are constrained and driven by natural, socio-economic, and techno-economic processes. Based on the concept of ‘land function’ and beyond a traditional land use model, the Land-Use based Integrated Sustainability Assessment (LUISA) modelling platform adopts a new approach towards activity-based modelling based upon the endogenous dynamic allocation of population, services and activities. The ultimate product of LUISA is a set of territorial indicators that can be grouped and combined according to the ‘land function’ of interest and/or to the sector under assessment. The herein presented indicators measure the provision of land functions in the period 2010-2050, according to the EU Reference Scenario (LUISA, updated configuration 2014), consistent with settings (economic and demographic in particular) and policies in place in 2013 (hence including the 2020 renewable energy targets). The indicators are aggregated by Member States and Regions (Administrative Units NUTS-2) and can be employed as benchmark to monitor sectorial and territorial evolutions of alternative scenarios (e.g. to simulate policy options or specific measures), and for future updates of the reference scenario, to capture policy impacts (for example when changing energy targets) and their territorial effects. This catalogue aims to provide the description of the land functions and the list of related indicators and an indicator factsheet (metadata). 30 indicators, out of the more than 50 currently produced by LUISA, are included in the first release of the catalogue. The catalogue is periodically up-dated, following the updates of the configurations of the LUISA modelling platform and the definition, computation and validation of new indicators. Indicators and basic spatial layers used for the simulations will be made available in the frame of the framework for the management of knowledge and dissemination of information being set up by the Pilot Knowledge Centre on Territorial Policies.JRC.H.8-Sustainability Assessmen

De membraanvervormende activiteit van Hsc70-4 bevordert de afbraak van synaptische proteïnen door endosomale microautofagie

Synapses are often far from their cell bodies and must cope largely independently with dysfunctional proteins resulting from synaptic activity and stress. Protein quality control pathways are involved in the clearance of these dysfunctional proteins, however for some of these pathways, not much is known about their role at synapses. Hence, the main goal of this doctoral thesis is to further inquire into protein quality control at nerve terminals. In this work, we found that endosomal microautophagy, a protein degradation pathway, is active at nerve terminals in Drosophila. In endosomal microautophagy, Hsc70-4, a molecular chaperon, targets substrates with a recognition motif to late endosomes where the substrates are engulfed by the endosomal membrane. Moreover, we found that this pathway requires a novel function of Hsc70-4, namely membrane deformation. In an in vitro tubulation screen, performed in our lab, Hsc70-4 was identified as a membrane deforming protein. Since it was shown that this chaperone is involved endosomal microautophagy that requires reshaping of the endosomal membrane to take up substrate proteins, we hypothesize that this novel function of Hsc70-4 could be implicated in endosomal microautophagy at the synapse. Since this pathway has never been studied in neurons before, we designed a microautophagy sensor, which allowed us to observe the presence of this pathway at Drosophila neuromuscular junctions (NMJs). We found that this pathway requires Hsc70-4’s membrane deformation activity, but not its chaperone activity. Additionally, we showed that Sgt, a known co-chaperone of Hsc70-4, promotes Hsc70-4’s protein refolding activity and blocks synaptic microautophagy. This suggests a regulatory role for Sgt on these two functions of Hsc70-4. We observed that synaptic proteins with a specific recognition motif can be targeted by Hsc70-4 for degradation by microautophagy, while Sgt on the other hand seems to block their turnover via this pathway. Finally, we observe that loss of microautophagy reduces neurotransmission while increasing microautophagic activity increases neurotransmission. We suggest that increased microautophagy rejuvenates the synaptic protein pool, resulting in more competent machinery for neurotransmitter release. With this work, we unraveled a new protein quality control pathway at the synapse that can specifically target proteins for degradation.status: publishe

Parents' perspectives on grounds for out-of-home placement of young children with a disability

This study investigated from the parents' perspective what reasons influenced their decision to place their child with a disability in residential care, what alternatives might have delayed or prevented it and how they feel about the decision. A multiple case study was used consisting of 15 families who had chosen to place their child under the age of 6 years in residential care. Data were collected by semi-structured interviews. The results confirm that families are looking for a balance between the interests of all family members. Four family types with the same patterns of child, family and context factors, in combination with specific motives for out-of-home placement, are described. Family support services were perceived by the parents as not fulfilling their needs. Although it was a difficult decision, parents do not regret placing their child. Recommendations are formulated to improve family support services.01status: publishe