Der Einfluss von SynCAM1 auf die Stabilisierung synaptischer Spines : eine in vivo Analyse

Die Verknüpfung von Nervenzellen durch Synapsen ist essentiell für die Funktion des Gehirns. Unnatürliche synaptische Strukturen sind dabei ein Merkmal neurodegenerativer Erkrankungen. Für therapeutische Ansätze und zum Verständnis der Arbeitsweise des Gehirns sind Untersuchungen zur Entstehung und Stabilität von Synapsen unerlässlich, da der zugrundeliegende Mechanismus nur unvollständig verstanden ist. Zelladhäsionsproteine wie das Immunglobulin-Protein SynCAM1 (Synaptic cell adhesion molecule 1) sind mögliche Regulatoren für die Entwicklung und Stabilität von Synapsen. In dieser Arbeit wurde der Einfluss von SynCAM1 auf die Bildung und Stabilität von dendritischen Spines untersucht. Mit Hilfe der Zwei-Photonen-Mikroskopie wurden in vivo Aufnahmen von Spines im Cortex im Abstand von einigen Tagen bis zu Monaten durchgeführt, um den Lebenszyklus einzelner Spines zu verfolgen. Dazu wurde ein Zwei-Photonen-Mikroskop konzipiert und aufgebaut, mit dem anschließend die in vivo Aufnahmen durchgeführt wurden. Um zu untersuchen, ob das Zelladhäsionsmolekül SynCAM1 einen Einfluss auf die Bildung und Stabilität von Synapsen hat, wurden sowohl SynCAM1flag überexprimierende als auch SynCAM1 Knockout-Mäuse analysiert. Dieses Vorgehen erlaubt die Betrachtung von Spines unter einem erhöhten SynCAM1 Proteinlevel sowie in Abwesenheit von SynCAM1. In beiden Mauslinien wurde die dynamische Änderung der dendritischen Spines ermittelt und verglichen. Dazu wurde die Anzahl der neugebildeten Spines, der Verlust bestehender Spines sowie die Stabilität von Spines mit Hilfe selbstgeschriebener Software ausgewertet. In den SynCAM1flag Überexpressionstieren zeigte sich dabei, dass Spines stabiler sind und eine verlängerte Lebensdauer haben. Der Anteil Filopodia-ähnlicher Spines wird außerdem durch die Überexpression von SynCAM1flag verringert. Gleichzeitig haben neugebildete Spines infolge der SynCAM1flag Überexpression eine erhöhte Überlebenschance. Letztendlich führt die Überexpression von SynCAM1 zum Anstieg der Spinedichte. Interessanterweise verbleibt die Spinedichte erhöht auch nachdem die SynCAM1flag Überexpession wieder abgeschaltet wurde. Die SynCAM1 Knockout-Mäuse liefern dazu komplementäre Ergebnisse. Die Spines der SynCAM1 Knockout-Tiere sind deutlich instabiler und haben eine verminderte Lebensdauer. Der Anteil Filopodia-ähnlicher Spines der Knockout-Tiere ist ferner stark erhöht. Weiterhin ist die Überlebensrate von neugebildeten Spines vermindert. Überdies ist die Spinedichte der SynCAM1 Knockout-Tiere verringert. Aus den gemachten Beobachtungen lässt sich schlussfolgern, dass SynCAM1 eine Schlüsselrolle in der Entwicklung und Stabilität von Spines übernimmt. Es konnte in dieser Arbeit der direkte Zusammenhang vom Expressionslevel eines synaptischen Adhäsionsproteins mit der Stabilität von dendritischen Spines in vivo nachgewiesen werden. Zusammenfassend belegen die vorgestellten Ergebnisse einen starken Einfluss von SynCAM1 auf die Lebensdauer und Entwicklung von Spines. Damit konnte SynCAM1 als wichtiger Mediator für die Bildung und den Erhalt von Synapsen im Gehirn identifiziert werden

Multi-stage optimisation towards transformation pathways for municipal energy systems

An essential facet of achieving climate neutrality by 2045 is the decarbonization of municipal energy systems. To accomplish this, it is necessary to establish implementation concepts that detail the timing, location, and specific measures required to achieve decarbonization. This restructuring process involves identifying the measures that offer the most compelling techno-economic and ecological advantages. In particular, measures that contribute to the interconnection of energy vectors and domains, e.g. heating, cooling, and electricity supply, in the sense of decentralized multi-energy systems are a promising future development option. Due to the high complexity resulting from a multitude of decision options as well as a temporal coupling across the transformation path, the use of optimization methods is required, which enable a bottom-up identification of suitable transformation solutions in a high spatial resolution. For the design of reasonable concepts, we develop a multistage optimization problem for the derivation of transformation pathways in the context of a multi-location structure, expansion, and operation problem. The results show that the heat supply in the future will mainly be provided by heat pumps with a share of 60%. It can also be shown that an early dismantling of the gas network will lead to the need for transitional technologies such as pellet heating. Overall, the conversion of the municipal energy system can significantly reduce emissions (97%).Comment: 13 pages, 11 figure

Usability of Digital Repository Software: A Study of DSpace Installation and Configuration

Abstract. Usability of the installation and configuration of digital repository software is a key factor for the implementation of digital repositories. Many universities, laboratories and companies want to place their collections online but the installation and configuration processes of digital repositories are sometimes time-consuming and unnecessarily complicated. This paper describes efforts to highlight usability issues while setting up and configuring DSpace. The focus of three studies that were performed was not end-user usability but usability of the administrative functionality. User evaluations performed on a recent version of DSpace were followed by participatory design of a tool to increase usability by abstracting away the lower-level details. Users agreed that such a tool would be suitably usable. Thus it was found that significant usability problems exist, but these problems may in fact be easily addressed

Neddylation regulates excitatory synaptic transmission and plasticity

Post-translational modifications, like phosphorylation, ubiquitylation, and sumoylation, have been shown to impact on synaptic neurotransmission by modifying pre- and postsynaptic proteins and therefore alter protein stability, localization, or protein-protein interactions. Previous studies showed that post-translational modifications are essential during the induction of synaptic plasticity, defined by a major reorganization of synaptic proteins. We demonstrated before that neddylation, a post-translational modification that covalently binds Nedd8 to lysine-residues, strongly affects neuronal maturation and spine stability. We now analysed the consequences of inhibiting neddylation on excitatory synaptic transmission and plasticity, which will help to narrow down possible targets, to make educated guesses, and test specific candidates. Here, we show that acute inhibition of neddylation impacts on synaptic neurotransmission before morphological changes occur. Our data indicate that pre- and postsynaptic proteins are neddylated since the inhibition of neddylation impacts on presynaptic release probability and postsynaptic receptor stabilization. In addition, blocking neddylation during the induction of long-term potentiation and long-term inhibition abolished both forms of synaptic plasticity. Therefore, this study shows the importance of identifying synaptic targets of the neddylation pathway to understand the regulation of synaptic transmission and plasticity.Fil: Brockmann, Marisa M.. Universitat Bonn; Alemania. Max Planck Institute Of Psychiatry; AlemaniaFil: Döngi, Michael. Universitat Bonn; AlemaniaFil: Einsfelder, Ulf. Universitat Bonn; AlemaniaFil: Körber, Nils. Universitat Bonn; AlemaniaFil: Refojo, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Stein, Valentin. Universitat Bonn; Alemani

Enhancing Usability of Open Source Digital Repository Software

Usability of the installation and configuration of digital repository software is a key factor for the implementation of digital repositories. Many universities, laboratories and companies want to place their collections online but the installation and configuration processes of digital repositories are sometimes time-consuming and unnecessarily complicated. This research attempts to make it easier to adopt, configure and use open source digital repository software. Usability issues while setting up and configuring DSpace will be highlighted and a system tool to improve on the usability is being developed. The focus of user studies is not end-user usability but usability of the administrative functionality. Exploratory studies have been performed on a recent version of DSpace, followed by participatory design of a tool to increase usability by abstracting away the lower-level details. Focused interventions are currently being applied to one or more tools to improve on the usability, for example by creating a generalisable cross-platform installation and configuration procedure. These interventions will ultimately be evaluated and assessed by typical users of the tools

Socio-economic development and migration in rural Ghana : report from field research in Amedzofe, Volta Region

Migration plays a significant role in Ghanaian society, particularly in rural areas where its impact is inextricably linked to socio-economic dynamics. In March 2023, a student field research field research project was conducted in Amedzofe as part of the international research project “Migration and Translocality in West Africa”, shedding light on various aspects of rural life through the lens of translocality. The field research aimed to address a wide range of topics related to rural livelihoods, focusing on migration and translocal aspects of everyday life. Six working groups embarked on a 10-day field research journey, employing mixed methods encompassing both quantitative and qualitative approaches. This extensive fieldwork followed a semester of intensive preparation, ensuring the thoroughness and depth of the study. The survey results were meticulously analysed and presented, providing valuable insights into the patterns, drivers and impacts of migration in the region. Additionally, the findings of the six working groups offered nuanced perspectives on various facets of rural life, including economic activities, social networks, cultural practices, education and gender aspects. This endeavour aims at fostering a deeper understanding of the complexities surrounding migration and translocality in rural Ghana. It is a testament to the dedication and vision of the late Prof. Dr. Malte Steinbrink, whose leadership and guidance were instrumental in the preparation and realisation of this study