Identifying systemic levers for transformation: : collaborative holistic system analysis by interdisciplinary scientists to support the climate justice movements to meet the 1.5° target

Background The impact of climate change and loss of biodiversity are threatening the resources of human existence and peace. Time is short for reaching the internationally agreed climate and sustainability goals by 2030. Civil societies, politicians, industries, and institutions search for policies and actions to facilitate, enable and realize transformations within all sectors: agriculture, forestry, energy and water supply, climate mitigation, buildings, transport, mobility, health and education. The transformation also concerns individual changes of behaviour. The main challenges lie in the complexity and interconnectivity of our system. However, many actions still follow a linear way of thinking. Growth-focussed pathways, goals and strategies prevent integrated and futureproof ecological, economic and social transformation. The climate justice movement “Fridays for Future” (FFF) has initiated first new ways of thinking and acting. Beyond scientific research the “Scientists for Future” (S4F) support the climate justice movement FFF on strategic communication and how to deal with opponents of an effective climate policy. Within this context, it was evident that a common understanding of the interdependencies, of levers and enhancements of transformation processes is essential. Methodology The steps for this holistic system analysis have their origin in the methodology of the “Sensitivity Model” by Prof. Frederic Vester, and in approaches by Donella Meadows and other pioneers in systems thinking and sustainability. In the recursive work- and learning process a set of 19 qualitative and quantitative variables was developed, which was later expanded to a total of 21 variables. The guiding question “How can Scientists for Future S4F support the climate justice movement (especially Fridays for Future) through scientific communication and other actions in such a way that sufficient decisions in all sectors are made so quickly that the "Paris climate targets" can still be achieved?” The project focused on a national level in Germany, while also considering the integration into European and international contexts. During the analysis, it became clear that the pursuit of sufficient climate protection is closely linked to achieving the 17 sustainability goals (SDGs). Validation, Conclusion, further Action The interpretation of the factors of influence, their impacts, and the analysis of the identified “control levers” and feedback cycles led to the conclusion that the effectiveness of public demonstrations or statements can only influence decisions on climate protection over a "long" distance, i. e. indirectly. However, the influence of decision-makers of the economy on political decision-making is much stronger than the influence of individual scientists or the entire movement. That influence mainly occurs through public "communication" (fast) and "education" (slow). It is necessary to influence "decision-makers in economy" and national regulatory frameworks in such a way that substantial effects on achieving the Paris targets can arise. The analysis showed the usefulness of systems thinking in order to establish an integrated view and action plan. The results will be communicated in regional S4F groups in order to establish a “Common Understanding” of the system and its relevant levers and control loops to support transformation towards sustainability and viability

Meprin β knockout reduces brain Aβ levels and rescues learning and memory impairments in the APP/lon mouse model for Alzheimer’s disease

β-Site amyloid precursor protein (APP) cleaving enzyme-1 (BACE1) is the major described β-secretase to generate Aβ peptides in Alzheimer’s disease (AD). However, all therapeutic attempts to block BACE1 activity and to improve AD symptoms have so far failed. A potential candidate for alternative Aβ peptides generation is the metalloproteinase meprin β, which cleaves APP predominantly at alanine in p2 and in this study we can detect an increased meprin β expression in AD brain. Here, we report the generation of the transgenic APP/lon mouse model of AD lacking the functional Mep1b gene (APP/lon × Mep1b−/−). We examined levels of canonical and truncated Aβ species using urea-SDS-PAGE, ELISA and immunohistochemistry in brains of APP/lon mouse × Mep1b−/−. Additionally, we investigated the cognitive abilities of these mice during the Morris water maze task. Aβ1-40 and 1–42 levels are reduced in APP/lon mice when meprin β is absent. Immunohistochemical staining of mouse brain sections revealed that N-terminally truncated Aβ2–x peptide deposition is decreased in APP/lon × Mep1b−/− mice. Importantly, loss of meprin β improved cognitive abilities and rescued learning behavior impairments in APP/lon mice. These observations indicate an important role of meprin β within the amyloidogenic pathway and Aβ production in vivo