Hedgehog signaling is required for the differentiation of ES cells into neurectoderm

AbstractMouse embryonic stem cells can differentiate in vitro into cells of the nervous system, neurons and glia. This differentiation mimics stages observed in vivo, including the generation of primitive ectoderm and neurectoderm in embryoid body culture. We demonstrate here that embryonic stem cell lines mutant for components of the Hedgehog signaling cascade are deficient at generating neurectoderm-containing embryoid bodies. The embryoid bodies derived from mutant cells are also unable to respond to retinoic acid treatment by producing nestin-positive neural stem cells, a response observed in cultures of heterozygous cells, and contain cores apparently arrested at the primitive ectoderm stage. The mutant cultures are also deficient in their capacity to differentiate into mature neurons and glia. These data are consistent with a role for Hedgehog signaling in generating neurectoderm capable of producing the appropriate neuronal and glial progenitors in ES cell culture

CCRI 2017 Year in Review

This book presents an overview of CCRI's research activities during 2017

A framework to assess the resilience of farming systems

Agricultural systems in Europe face accumulating economic, ecological and societal challenges, raising concerns about their resilience to shocks and stresses. These resilience issues need to be addressed with a focus on the regional context in which farming systems operate because farms, farmers’ organizations, service suppliers and supply chain actors are embedded in local environments and functions of agriculture. We define resilience of a farming system as its ability to ensure the provision of the system functions in the face of increasingly complex and accumulating economic, social, environmental and institutional shocks and stresses, through capacities of robustness, adaptability and transformability. We (i) develop a framework to assess the resilience of farming systems, and (ii) present a methodology to operationalize the framework with a view to Europe’s diverse farming systems. The framework is designed to assess resilience to specific challenges (specified resilience) as well as a farming system’s capacity to deal with the unknown, uncertainty and surprise (general resilience). The framework provides a heuristic to analyze system properties, challenges (shocks, long-term stresses), indicators to measure the performance of system functions, resilience capacities and resilience-enhancing attributes. Capacities and attributes refer to adaptive cycle processes of agricultural practices, farm demographics, governance and risk management. The novelty of the framework pertains to the focal scale of analysis, i.e. the farming system level, the consideration of accumulating challenges and various agricultural processes, and the consideration that farming systems provide multiple functions that can change over time. Furthermore, the distinction between three resilience capacities (robustness, adaptability, transformability) ensures that the framework goes beyond narrow definitions that limit resilience to robustness. The methodology deploys a mixed-methods approach: quantitative methods, such as statistics, econometrics and modelling, are used to identify underlying patterns, causal explanations and likely contributing factors; while qualitative methods, such as interviews, participatory approaches and stakeholder workshops, access experiential and contextual knowledge and provide more nuanced insights. More specifically, analysis along the framework explores multiple nested levels of farming systems (e.g. farm, farm household, supply chain, farming system) over a time horizon of 1-2 generations, thereby enabling reflection on potential temporal and scalar trade-offs across resilience attributes. The richness of the framework is illustrated for the arable farming system in Veenkoloniën, the Netherlands. The analysis reveals a relatively low capacity of this farming system to transform and farmers feeling distressed about transformation, while other members of their households have experienced many examples of transformation

Biography – A Play? Poetologische Experimente mit einer Gattung ohne Poetik

Im Unterschied zu vielen Genres in der abendländischen Tradition gibt es für biographisches Schreiben keine Gattungspoetiken, nur Prototypen, Vorbilder, und die bis heute dominante Erzählordnung ist die chronologische. Kausal- und Finalnexus eines Lebens werden so in wissenschaftlichen wie literarischen Biographien in der Regel behauptet und miteinander verbunden. Die Aufsätze dieses Bandes stellen im Kontrast dazu Variationsmöglichkeiten biographischer Poetologie vor, historische wie gegenwärtige Experimente, (inter-)mediale Spielformen wie Alternativen der Narration. Einige der Beiträge sind zugleich Werkstattberichte von Biographen, die Auskunft über die Konstruktionsprinzipien ihres Schreibens geben. Der Titel des Bandes bezieht sich auf Max Frischs Theaterstück Biografie: Ein Spiel, das 1967 entstand und 1968 im Schauspielhaus Zürich uraufgeführt wurde, und variiert dessen Ausgangsbedingung, ersetzt den Registrator, der dem Helden Kürmann erlaubt, sein Leben – immer wieder dessen entscheidende Situationen verändernd – neu zu leben, durch den Biographen, der die Vita des Biographierten in allen ihren Handlungsoptionen als ein offenes Experiment zu beschreiben versucht

D5.3 Resilience assessment of current farming systems across the European Union

For improving sustainability and resilience of EU farming system, the current state needs to be assessed, before being able to move on to future scenarios. Assessing sustainability and resilience of farming systems is a multi-faceted research challenge in terms of the scientific domains and scales of integration (farm, household, farming system level) that need to be covered. Hence, in SURE-Farm, multiple approaches are used to evaluate current sustainability and resilience and its underlying structures and drivers. To maintain consistency across the different approaches, all approaches are connected to a resilience framework which was developed for the unique purposes of SURE-Farm. The resilience framework follows five steps: 1) the farming system (resilience of what?), 2) challenges (resilience to what?), 3) functions (resilience for what purpose?), 4) resilience capacities, 5) resilience attributes (what enhances resilience?). The framework was operationalized in 11 case studies across the EU. Applied approaches differ in disciplinary orientation and the farming system process they focus on. Three approaches focus on risk management: 1) a farm survey with a main focus on risk management and risk management strategies, 2) interviews on farmers’ learning capacity and networks of influence, and 3) Focus Groups on risk management. Two approaches address farm demographics: 4) interviews on farm demographics, and 5) AgriPoliS Focus Group workshops on structural change of farming systems from a (farm) demographics perspective. One approach applied so far addresses governance: 6) the Resilience Assessment Tool that evaluates how policies and legislation support resilience of farming systems. Two methods address agricultural production and delivery of public and private goods: 7) the Framework of Participatory Impact Assessment for sustainable and resilient farming systems (FoPIA-SURE-Farm), aiming to integrate multiple perspectives at farming system level, and 8) the Ecosystem Services assessment that evaluates the delivery of public and private goods. In a few case studies, additional methods were applied. Specifically, in the Italian case study, additional statistical approaches were used to increase the support for risk management options (Appendix A and Appendix B). Results of the different methods were compared and synthesized per step of the resilience framework. Synthesized results were used to determine the position of the farming system in the adaptive cycle, i.e. in the exploitation, conservation, release, or reorganization phase. Dependent on the current phase of the farming system, strategies for improving sustainability and resilience were developed. Results were synthesized around the three aspects characterizing the SURE-Farm framework, i.e. (i) it studies resilience at the farming system level, (ii) considers three resilience capacities, and (iii) assesses resilience in the context of the (changing) functions of the system. (i) Many actors are part of the farming system. However, resilience-enhancing strategies are mostly defined at the farm level. In each farming system multiple actors are considered to be part of the system, such as consultants, neighbors, local selling networks and nature organizations. The number of different farming system actors beyond the focal farmers varies between 4 (in French beef and Italian hazelnut systems) and 14 (large-scale arable systems in the UK). These large numbers of actors illustrate the relevance of looking at farming system level rather than at farm level. It also suggests that discussions about resilience and future strategies need to embrace all of these actors. (ii) At system level there is a low perceived capacity to transform. Yet, most systems appear to be at the start of a period in which (incremental) transformation is required. At system level, the capacity to transform is perceived to be relatively low, except in the Romanian mixed farming system. The latter may reflect a combination of ample room to grow and a relatively stable environment (especially when compared to the past 30 to 50 years). The relatively low capacity to transform in the majority of systems is not in line with the suggestion that most systems are at the start of (incremental) transformation, or, at least, reached a situation in which they can no longer grow. Further growth is only deemed possible in the Belgium dairy, Italian hazelnut, Polish fruit and Romanian mixed farming systems. (iii) System functions score well with regard to the delivery of high-quality and safe food but face problems with quality of rural life and protecting biodiversity. Resilience capacities can only be understood in the context of the functions to be delivered by a farming system. We find that across all systems required functions are a mix of private and public goods. With regard to the capacity to deliver private goods, all systems perform well with respect to high-quality and safe food. Viability of farm income is regarded moderate or low in the livestock systems in Belgium (dairy), France (beef) and Sweden (broilers), and the fruit farming system in Poland. Across all functions, attention is especially needed for the delivery of public goods. More specifically the quality of rural life and infrastructure are frequently classified as being important, but currently performing bad. Despite the concerns about the delivery of public goods, many future strategies still focus on improving the delivery of private goods. Suggestions in the area of public goods include among others the implementation of conservation farming in the UK arable system, improved water management in the Italian hazelnut system, and introduction of technologies which reduce the use of herbicides in Polish fruit systems. It is questionable whether these are sufficient to address the need to improve the maintenance of natural resources, biodiversity and attractiveness of rural areas. With regard to the changing of functions over time, we did not find evidence for this in our farming systems

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Impact of COVID-19 on farming systems in Europe through the lens of resilience thinking

CONTEXT Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. OBJECTIVE This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems’ social and institutional environment. METHODS The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. RESULTS AND CONCLUSIONS Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already played before the crisis, they persisted during the crisis. Also, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics importantly contributed to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. SIGNIFICANCE Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment