Pioneer transcription factor interactions and chromatin binding dynamics during zygotic genome activation

Cell fate transitions are regulated by the activity of factors such as pioneer transcription factors (PTFs) to promote new transcriptional programmes. PTFs can bind to closed chromatin, and often interact with other PTFs and chromatin remodelers, to make chromatin accessible for transcription. How PTFs dynamically bind DNA and interact with each other to achieve this has mainly been studied in vitro. Zygotic Genome Activation (ZGA) is an excellent model to study the dynamics of PTFs in the context of gene expression in vivo, as transcription begins from a previously silent genome. In this thesis I aimed to harness live quantitative microscopy to study the interactions and chromatin binding dynamics of the PTFs Nanog, Pou5f3, and Sox19b required for ZGA in zebrafish. I first verified whether Fluorescence Correlation Spectroscopy (FCS) can be used to examine PTF chromatin-bound diffusion. After optimising the tagging strategy, sample preparation and measurement, as well as the analysis by autocorrelation and curve fitting, I showed that FCS can measure the diffusion of fluorescently-tagged PTFs at ZGA. However, I found no significant difference in diffusion between Nanog-Citrine and mCherry-Pou5f3, or changes to their diffusion as ZGA progresses. This suggests that the short-lived chromatin interactions measured by FCS, which may reflect TF DNA motif search, remain constant for Nanog and Pou5f3 during ZGA. Next, I wanted to test whether Nanog, Sox19b and Pou5f3 directly interact during ZGA. The spectral proximity of (m)Citrine and mCherry made these an unsuitable fluorophore pair for Fluorescence Cross-Correlation Spectroscopy, but allowed me to use Foerster Resonance Energy Transfer (FRET) assays. I began by showing that mCitrine and mCherry are indeed a good FRET pair. I then moved on to measure FRET by changes to the donor lifetime, as this method is less susceptible to concentration and photobleaching. For this, I used a semi-quantitative lifetime-based measure, Average Arrival Time (AAT), which does not require fitting analysis and therefore performs better in systems with low signal-to-noise ratio. Optimising sample preparation, image acquisition, and data analysis allowed me to detect interactions between controls in zebrafish embryos: the AAT of mCitrine was slightly but significantly lower in the mCitrine-mCherry tandem fusion, compared to negative controls. I then showed that Nanog-mCitrine and Sox19b-mCherry may interact at ZGA, however the low resolution of AAT measurements paired with the slight mCitrine AAT shift limited any further investigation. To efficiently probe PTF-PTF interactions by AAT-FRET, an alternative FRET pair in which the donor undergoes a larger lifetime shift would be required. Overall, I have found that the target-search dynamics of Nanog and Pou5f3 may not differ significantly throughout ZGA, and that Nanog and Sox19b may interact. However my data were significantly limited by the fluorophore choice and the low signal-to-noise ratio. Further optimisations to the experimental setup would help to quantify more reliably how the PTFs behave dynamically to regulate transcriptional onset at ZGA

Second International Workshop on Linked Data-driven Resilience Research 2023

In the face of continuously changing contextual conditions and ubiquitous disruptive crisis events, the concept of resilience refers to some of the most urgent, challenging, and interesting issues of nowadays society. Economic value networks, technical infrastructures, health systems, and social textures alike need to unfold capacities to withstand, adapt, recover, or even refine and transform themselves to stay ahead of changes

Auswirkungen von Androstadienon auf das menschliche Verhalten

Androstadienon (AND) ist ein Chemosignal, das z.B. im menschlichen Körperschweiß vorkommt. Im Rahmen dieser Arbeit soll systematisch gesammelt werden, ob in der Literatur konsistente Einflüsse von AND auf bestimmte Verhaltensreaktionen bei Menschen aufgezeigt wurden bzw. ob und wie AND unter besonderen Voraussetzungen wirkt. Dies wurde mittels systematischem Review erzielt. Mittels PRISMA Leitlinie wurde die Literatur strukturiert und analysiert. Die Ergebnisse von 24 Originalstudien, welche Verhaltensdaten unter Einfluss von AND veröffentlicht hatten, wurden in vier verschiedenen Kategorien miteinander verglichen: Auswirkungen auf das soziale Verhalten, auf die emotionale Reizverarbeitung bzw. Emotionsbewertung, auf die Attraktivitätsbewertung und Partnerwahl sowie Wachsamkeit und Gedächtnisleistung. Aufgrund unterschiedlicher Studiendesigns, unterschiedlicher Stichproben, Studienaufgaben, Konzentrationen und Präsentationen von AND sowie Inhomogenität der berichteten Ergebnisse konnte kein konsistenter Effekt von AND auf das Verhalten von Menschen aufgezeigt werden. Zum anderen wurde die Frage gestellt, ob AND unterschiedliche Einflüsse auf Menschen hat, welche den Geruch von AND als angenehm oder unangenehm empfinden – hierfür wurden die Teilnehmenden einer Verhaltensstudie anhand Mediansplits hinsichtlich der Bewertung, wie angenehm sie die AND-Lösung empfunden haben, in zwei Gruppen geteilt und Unterschiede in Bezug auf zwei Aufmerksamkeitsprozesse untersucht. Vergleichbar zum systematischen Review konnte auch in der Verhaltensstudie kein konsistenter Effekt der subjektiv wahrgenommenen Annehmlichkeit von AND auf unterschiedliche Aufmerksamkeitsprozesse festgestellt werden. Zusammenfassend zeigt sich eine Inkonsistenz der publizierten Auswirkung von AND im systematischen Review. In der eigenen Studie konnten wir keinen Effekt der Annehmlichkeit von AND auf Aufmerksamkeitseffekte zeigen. Es bleibt daher offen, welchen Effekt AND tatsächlich auf menschliches Verhalten ausübt und zukünftige Forschung wird zeigen, welchen (konsistenten) Einfluss Chemosignale auf die menschliche Kommunikation haben

Retrospective pathology review of captive black rhinoceros Diceros bicornis in the EAZA Ex-situ Programme (1995-2022)

The husbandry of black rhinoceros Diceros bicornis is challenging due to a number of peculiar diseases affecting this species. Causes of mortality and morbidity were evaluated from 67 necropsy reports of black rhinos deceased in the EAZA Ex-situ Programme (EEP) in 1995–2022, and the prevalence of specific diseases were compared with previous surveys in the literature. Whereas some problems described as typical, such as haemolytic anaemia, aspergillosis or specific skin diseases presented at low prevalence, signs of iron overload disorder (IOD) were close to ubiquitous across animals, and skin disease, excessive tooth wear (often linked to impaction) and gastric ulceration were particularly prevalent. While this evaluation cannot add to understanding of the aetiology of these conditions, it emphasises the need to further investigate IOD and other diseases (which will require access to routine blood samples of both healthy and diseased animals facilitated by medical training). The findings also recommend further investigation of measures to rdce stress, possibly including that triggered by conspecifics as well as humans. Species-adequate nutrition still requires proactive approaches in providing dicot-based forages without resorting to monocot (grass) products

Cu(111) single crystal electrodes: Modifying interfacial properties to tailor electrocatalysis

Tailoring electrocatalyst materials to the specific requirements of a certain reaction and to optimize activity or enhance selectivity is a key tactic for the development of low-temperature fuel and electrolyzer cells for clean energy production. Here, we demonstrate the modification of Cu(111) electrodes with different sub-monolayer coverages of foreign metals (Cd) and metal hydroxides (Co(OH)2 and Ni(OH)2) for application in the hydrogen evolution reaction (HER) in alkaline media. In situ electrochemical scanning tunneling microscopy (EC-STM) reveals that these modifications have a significant influence on the morphology and structure of the Cu(111) surface with its characteristics depending on both the nature and the amount of the adsorbed metal(hydroxide). Ni(OH)2 and Co(OH)2 on Cu(111) lead to a significant enhancement of the electrocatalytic activity towards the HER in alkaline electrolyte, whereas a decrease in activity is found for Cd modified Cu(111). These trends can be rationalized by considering the strength of the interfacial electric field and its influence on the specific interactions of the electrode with the water ad-layer close to the surface, as determined by laser-induced temperature jump measurements. This comparative study therefore provides valuable information on the structure-activity relation as well as insights on the interfacial characteristics of different bimetallic Cu electrocatalysts.A.A. is a recipient of a doctorate (DOC) Fellowship of the Austrian Academy of Sciences at the Institute of Physical Chemistry. C.G. thanks the Austrian Research Promotion Agency (FFG) for funding by the project number 870523. J.K-L. acknowledges funding by the Austrian Science Fund (FWF) via grant I-4114-N37. J.M.F and V.C. acknowledge financial support from Ministerio de Ciencia e Innovación (project PID2019-105653GB-100) and Generalitat Valenciana (project PROMETEO/2020/063)

Collaborative Work on Ontologies - A Report

Supply chains are vulnerable and inherently complex processes. In-creasing the resilience of supply chains is realised, if the stakeholders involved have agreed on a clear language. Only this enables a comprehensive, unambiguous and fast exchange of information. Ontologies serve as a powerful formal tool to realize an appropriate communication framework. They are designed to make communication and information exchange between stakeholders and machines unambiguous and thus efficient. This paper addresses the challenges and solutions associated with the fact that ontologies need to reflect agreed definitions of a domain, as we face them in the SC3 and CoyPu projects

Interfacial Water Structure as a Descriptor for Its Electro-Reduction on Ni(OH)2-Modified Cu(111)

The hydrogen evolution reaction (HER) has been crucial for the development of fundamental knowledge on electrocatalysis and electrochemistry, in general. In alkaline media, many key questions concerning pH-dependent structure–activity relations and the underlying activity descriptors remain unclear. While the presence of Ni(OH)2 deposited on Pt(111) has been shown to highly improve the rate of the HER through the electrode’s bifunctionality, no studies exist on how low coverages of Ni(OH)2 influence the electrocatalytic behavior of Cu surfaces, which is a low-cost alternative to Pt. Here, we demonstrate that Cu(111) modified with 0.1 and 0.2 monolayers (ML) of Ni(OH)2 exhibits an unusual non-linear activity trend with increasing coverage. By combining in situ structural investigations with studies on the interfacial water orientation using electrochemical scanning tunneling microscopy and laser-induced temperature jump experiments, we find a correlation between a particular threshold of surface roughness and the decrease in the ordering of the water network at the interface. The highly disordered water ad-layer close to the onset of the HER, which is only present for 0.2 ML of Ni(OH)2, facilitates the reorganization of the interfacial water molecules to accommodate for charge transfer, thus enhancing the rate of the reaction. These findings strongly suggest a general validity of the interfacial water reorganization as an activity descriptor for the HER in alkaline media.A.A. is a recipient of a doctorate (DOC) Fellowship of the Austrian Academy of Sciences at the Institute of Physical Chemistry. C.G. thanks the Austrian Research Promotion Agency (FFG) for funding via the project number 870523. J.K.-L. acknowledges funding by the Austrian Science Fund (FWF) via grant I-4114-N37. J.M.F. and V.C. acknowledge financial support from Ministerio de Ciencia e Innovación (project PID2019-105653GB-100) and Generalitat Valenciana (project PROMETEO/2020/063)

PowerDynamics.jl—An experimentally validated open-source package for the dynamical analysis of power grids

PowerDynamics.jl is a Julia package for time-domain modeling of power grids that is specifically designed for the stability analysis of systems with high shares of renewable energies. It makes use of Julia’s state-of-the-art differential equation solvers and is highly performant even for systems with a large number of components. Further, it is compatible with Julia’s machine learning libraries and allows for the utilization of these methods for dynamical optimization and parameter fitting. The package comes with a number of predefined models for synchronous machines, transmission lines and inverter systems. However, the strict open-source approach and a macro-based user-interface also allows for an easy implementation of custom-built models which makes it especially interesting for the design and testing of new control strategies for distributed generation units. This paper presents how the modeling concept, implemented component models and fault scenarios have been experimentally tested against measurements in the microgrid lab of TECNALIA.This research has been performed using the ERIGrid Research Infrastructure and is part of a project that has received funding from the European Union’s Horizon 2020 Research and Innova-tion Programme under the Grant Agreement No. 654113. The support of the European Research Infrastructure ERIGrid and its partner TECNALIA is very much appreciated. We further acknowl-edge the Support by BMBF(CoNDyNet2FK.03EK3055A), the DFG (ExSyCo-Grid, 410409736), the Leibniz competition (T42/2018) and the Federal Ministry of Economics (MAriE, FK. 03Ei4012B)

Collaborative and Cross-Stakeholder Ontology Engineering

One of the major challenges in developing ontologies is to efficiently merge domain knowledge and expert knowledge to enable efficient and effective work on formal modelling of the domain in focus. This paper outlines the current state of developments in the Semantically Connected Semiconductor Supply Chains (SC3) project and its application in the BMBF-funded Cognitive Economy Intelligence Platform for Economic Ecosystem Resilience (CoyPu) project. We are using the SC3 Ontology Platform in CoyPu to promote effective information sharing among the various stakeholders in the development of the ontology. Thus, the application of SC3 Ontology Platform is used to ensure that the knowledge of non-knowledge workers (domain experts) and knowledge workers come together efficiently. This paper first introduces the CoyPu project and the current ontology development; then the SC3 Ontology Platform and its main components are presented. The paper concludes with the analysis of a first usability evaluation