Ein zentrales Ziel des naturwissenschaftlichen Unterrichts ist die Förderung einer naturwissenschaftlichen Grundbildung (Scientific Literacy). Diese umfasst auch ein Verständnis über die Natur bzw. Kultur der Naturwissenschaften (Nature of Science, NOS). NOS beschreibt die Eigenschaften, Bedingungen und Grenzen naturwissenschaftlicher Erkenntnisprozesse. In der naturwissenschaftsdidaktischen Forschung wird intensiv diskutiert, welche NOS-Aspekte im Unterricht adressiert (inhaltliche Dimension) und wie diese dargestellt werden sollten (unterrichtsmethodische Dimension). Die Biologie, Chemie und Physik haben Gemeinsamkeiten, aber auch Unterschiede zueinander. Aus wissenschaftstheoretischer Perspektive lassen sich Besonderheiten biologischer Forschung auf spezifische Eigenschaften biologischer Forschungsobjekte zurückführen. Zudem hängt das NOS-Verständnis von Schüler:innen und Lehrkräften von der jeweils berücksichtigten Disziplin ab. Folglich sollten für eine differenzierte Analyse und Förderung des NOS-Verständnisses Unterschiede zwischen einzelnen naturwissenschaftlichen Disziplinen in einer Konzeptualisierung von NOS berücksichtigt werden. Mit dem Family Resemblance Approach (FRA) werden Naturwissenschaften wie Mitglieder einer Familie beschrieben, die Gemeinsamkeiten, aber auch Unterschiede zueinander aufweisen. Dadurch können neben disziplinübergreifenden auch disziplinspezifische NOS-Aspekte beschrieben werden. Ziel dieser Arbeit ist es, den FRA unter Berücksichtigung der Besonderheiten biologischer Forschung zu differenzieren und zu kontextualisieren, sowie aufzuzeigen, wie NOS-Aspekte in Unterrichtsmaterialien wie Schulbüchern dargestellt werden. Zudem soll anhand konkreter Lerngelegenheiten für den Biologieunterricht verdeutlicht werden, wie es gelingen kann, Besonderheiten der Biologie in die Unterrichtspraxis zu integrieren. Bezogen auf die inhaltliche Dimension wurden in einer Schulbuchstudie NOS-Aspekte, die im Biologie-Curriculum enthalten sind, beschrieben. Auf dieser Grundlage wurden in einer Interviewstudie mit Fachwissenschaftler:innen und Wissenschaftstheoretiker:innen biologiespezifische NOS-Konzepte entwickelt, mit denen Zusammenhänge zwischen den Eigenschaften biologischer Forschungsobjekte und Besonderheiten biologischer Forschung beschrieben werden. Bezogen auf die unterrichtsmethodische Dimension wurde untersucht, wie NOS in unterschiedlichen Kapiteln von Biologie-Schulbüchern dargestellt ist. Die Ergebnisse zeigen, dass NOS-Aspekte in den Einführungskapiteln signifikant häufiger explizit dargestellt sind als in fachlich kontextualisierten Kapiteln. Zudem wurde diskutiert, welche Möglichkeiten für eine Kontextualisierung von NOS in einer Lerngelegenheit für den Biologieunterricht bestehen. Auf Grundlage dieser Erkenntnisse wurden verschiedene Lerngelegenheiten in Form konkreter Vorschläge für die Praxis entwickelt, mit denen das NOS-Verständnis im Biologieunterricht gefördert werden kann. Insgesamt leistet diese Arbeit einen innovativen Beitrag in der fachdidaktischen NOS-Forschung, indem auf Grundlage des FRA empirisch gestützte biologiespezifische NOS-Konzepte aus curricularer, fachwissenschaftlicher und wissenschaftstheoretischer Perspektive entwickelt wurden. Zudem konnten anhand der empirischen Erkenntnisse konkrete Möglichkeiten für die Gestaltung von Unterrichtsmaterialien für den Biologieunterricht aufgezeigt werden.

Transposable elements (TEs) and their repressors, KRAB zinc finger proteins (KRAB-ZNF proteins), play pivotal roles in shaping regulatory innovation during vertebrate evolution, particularly in primates. This study introduces TEKRABber, a computational framework developed to enable systematic analysis and cross-species comparison of TE expression and KRAB-ZNF interactions. TEKRABber provides standardized normalization and differential expression analysis of TE subfamilies using outputs from various RNA-seq quantification tools, facilitating downstream exploration of TE–gene and TE–KRAB-ZNF relationships within and between species.

Application of TEKRABber to multiple RNA-seq datasets, including human cortical samples from healthy and Alzheimer’s disease patients as well as brain tissues from four primate species, revealed evolutionary patterns in KRAB-ZNF–TE regulatory networks. Bipartite network analysis identified an increased number of KRAB-ZNF–TE interactions in humans compared to other primates, particularly involving recently evolved TEs such as Alu elements. Notably, ZNF528 , a KRAB-ZNF gene under positive selection in the human lineage, showed numerous human-specific interactions. Negative correlations were primarily observed with Alu elements, consistent with transcriptional repression, while other TEs were more frequently associated with positive correlations. In Alzheimer’s disease samples, a regulatory subnetwork consisting of 21 Alu-associated interactions appeared reduced or absent, suggesting a potential link between TE dysregulation and neurodegeneration.

To investigate the molecular basis of these interactions, multi-omic integration of KAP1 ChIP-seq and RNA-seq data from B-lymphoblastoid cells (B cells) of humans, chimpanzees, and orangutans was performed. Thousands of species-specific KAP1-binding sites were identified, the majority of which overlapped with TEs located in intronic or intergenic regions. Genes proximal to KAP1 peaks in non-human primates were enriched for neuronal development functions and more frequently downregulated than in humans. Locus-specific TE expression profiles were incorporated into downstream analyses with TEKRABber, enabling detailed comparisons of transcriptional activity across species. These analyses revealed that KAP1-bound TE loci are generally transcriptionally repressed. By combining motif analysis, gene expression, and binding profiles, species-specific regulatory networks were reconstructed, linking differentially expressed KRAB-ZNF genes to their putative targets. These findings underscore the utility of TEKRABber in integrating multi-modal data and support the hypothesis that the evolving interplay between KRAB-ZNFs and TEs contributes to lineage-specific gene regulation and primate brain evolution.

Storing energy from renewable but intermittent energy sources such as wind and solar into chemical bonds is one of the most promising strategies we have for transiting from fossil fuel-based technologies and addressing the environmental challenges we currently face. A vital part of this strategy is the production of hydrogen through electrochemical water splitting, where the oxygen evolution reaction (OER) is still a fundamental bottleneck and the rate-limiting part of the reaction. Recent efforts have focused on developing efficient electrocatalysts for alkaline electrolysis using earth-abundant materials such as 3d transition metal oxides and hydroxides based on Ni and Co. Notably, it has been found in previous work that cationic species in the electrolyte can strongly influence the properties of these materials. The exact impact of these species and how they alter the catalyst morphology under reaction conditions, however, remain poorly understood due to lack of in situ and operando microscopy investigations that reveal such changes at the nanoscale. Among the impurities relevant to OER, iron (Fe) is particularly influential. It has been widely reported that incorporating Fe into Ni or Co-based OER catalysts, whether intentionally or unintentionally, significantly enhances their OER activity. However, obtaining direct insight into how Fe alters the structure of Ni and Co (hydro)oxides during the reaction remains a challenge, which in turn limits our understanding of the mechanisms behind its role. A major part of my thesis focuses on revealing the effect of Fe impurities in the electrolyte on catalyst morphology using state-of-the-art operando microscopy and spectroscopy methods, especially with electrochemical liquid-cell transmission electron microscopy (EC-TEM). In the latter part of the thesis, I will discuss the impact of a more innocuous but common cationic impurity, Na, on the long-term evolution of Ni hydroxides reacted in potassium hydroxide. In Chapter 3, I first describe the specific changes that occur in NiO when Fe is added into the electrolyte. To track the chemical changes arising from Fe impurities, I extended our EC-TEM study to incorporate time-resolved energy-dispersive X-ray spectroscopy (EDS) mapping of the samples under reaction conditions. These results together with supporting evidence from additional operando spectroscopy measurements on the same pre-catalysts revealed that when Fe is present in the electrolyte during OER, it transforms the NiO surface into a superficial layer of NiFe layered double hydroxide. This continuous transformation of the surface can be correlated with the beneficial shift in onset potential for water oxidation. The superficial layer, however, does not grow with further reaction time in the presence of Fe. Instead, Fe aggregates start to form once the NiO surface becomes saturated and these aggregates poison the surface, leading to a decrease in the anodic currents for OER. Building on the findings from Chapter 3, I extended our investigation to the incorporation of Fe into Co and Ni hydroxides (Chapter 4). Specifically, I studied the behavior of Co(OH)2 nanosheets and investigated their chemical and structural changes during OER, with and without Fe impurities, through correlated operando microscopy and spectroscopy. Here, operando scanning transmission X-ray microscopy measurements were performed to provide spatially resolved information about the catalyst oxidation state. The results revealed that Co(OH)2 underwent significant restructuring in Fe-free electrolytes by forming amorphous CoOxHy, which was accompanied by catalyst dissolution-redeposition where Co were redeposited as Co3+ or Co3+δ (hydr)oxide nanoparticles. In the presence of Fe, I saw significantly less redeposition and the formation of a stable Co(Fe)OOH phase on the surface, which I attributed to the reduced morphological changes. The lower average oxidation state of Co observed in our system is a direct consequence of this reduced dissolution-redeposition cycle, highlighting how the balance of restructuring, dissolution and redeposition alters the performance of Co-based catalysts and leads to a revised interpretation of the function of Fe versus that of the Co host during catalytic processes. In Chapter 5, this thesis broadens its scope to examine the influence of Na+ and K+ ions in a KOH electrolyte. Here, we compared the evolution of well-defined Ni(OH)2 nanoplates in NaOH, KOH and KOH with trace amounts but defined impurity concentration of Na+. Through both electrochemical and (operando) structural characterization, I show that even trace-amounts of Na+ ions in a KOH electrolyte accelerates the β- to γ-NiOOH phase transition of the catalyst, resulting in lower long-term OER activity. This is driven by the different intercalation behaviors of metal cations. Specifically, the β-NiOOH phase tends to overcharge into the γ-NiOOH phase upon intercalation of K+. The presence of Na+ ions, with their larger hydrated radius, further facilitates this overcharging in mixed electrolytes by expanding the interlayer structure. This work provides valuable new insights into the relationship between cation intercalation and surface restructuring in nickel-based catalysts. It also emphasizes the importance of controlling cation composition in the electrolyte to optimize OER performance. In summary, the work described in this thesis reveals the structural changes induced by cationic impurities in model Ni and Co-based pre-catalysts for OER. Scientifically, it highlights how we must consider the impact of the catalyst structural evolution under applied potential to obtain a more comprehensive understanding of these impurities and their associated effects. Another aspect of the work encompasses the advancement of multi-modal operando microscopy approaches, particularly with the incorporation of concurrent time-resolved EDS mapping and correlative operando investigations combining both electron and X-ray microscopy insights, which will inspire the use of similar approaches towards the study of functional materials under working conditions.

Pneumolysin (PLY) is a cholesterol-dependent cytolysin secreted by Streptococcus pneumoniae and a major virulence factor in invasive pneumococcal diseases, including pneumonia, meningitis, otitis media, and myocarditis. Importantly, PLY remains active even after bacterial lysis, and the increasing prevalence of antibiotic resistance highlights the urgent need for adjunct antivirulence therapies capable of directly neutralizing this toxin. This thesis focuses on the development and optimization of small-molecule PLY inhibitors, building upon the previously identified lead compound Pathoblocker 3 (PB.3). Although PB.3 exhibits potent PLY inhibition (IC₅₀ = 3.2 µM), its limited aqueous solubility and susceptibility to hydrolysis in phosphate-buffered saline constrain its therapeutic potential. The primary objective of this work was to improve the stability and solubility of PB.3-derived compounds while retaining or enhancing inhibitory activity. Using a scaffold-hopping approach, PB.3 was divided into three structural regions (A, B, and C) to enable systematic modification. A focused library of derivatives was synthesized using Knoevenagel, Henry, and Vilsmeier–Haack reactions, while Meerwein, CuAAC, and Suzuki reactions provided key intermediates. The resulting compounds were evaluated for aqueous stability and solubility, followed by assessment of PLY inhibition in a collaboratively performed hemolysis assay. Structure–activity relationship analysis identified thiophene as a superior replacement for the original furan ring, yielding compounds with complete aqueous stability and enhanced potency. Thiophene-containing derivatives, including compounds 9, 14, 23, and 40, displayed strong PLY inhibition with IC₅₀ values in the low micromolar range (~2–5 µM) and high stability. In contrast, pyrrole- and triazole-based modifications negatively affected stability. Alternative warheads, such as nitrovinyl and olefinic hydroxyl groups, improved stability but resulted in reduced inhibitory activity. Thiobarbituric acid derivatives exhibited excellent potency but showed impaired stability. Overall, this work identifies stable and potent PLY inhibitors and supports their further development as adjunct therapeutics to complement antibiotic treatment of pneumococcal infections.

The twenty-first century is the century of displacement. An unprecedented 125 million individu-als are currently displaced globally, with 40 million of them being internationally displaced and crossing international borders. The majority of these displaced individuals gravitate toward urban areas in search of asylum, protection, and sanctuary. However, within cities, internationally dis-placed migrants encounter formidable challenges arising from increasingly restrictive, violent, and market-driven migration regimes, rendering them vulnerable to social, economic, political, and legal insecurity. These challenges are compounded by a pervasive housing crisis and the proliferation of urban displacement phenomena, such as evictions and homelessness. These multifaceted processes and conditions continue to further displace those already displaced in-ternationally; and they multiply displacement processes and experiences. In this dissertation, I examine the enduring coercion and dispossession experienced by inter-nationally displaced migrants, demonstrating that such experiences persist and intensify long after migrants’ arrival in urban centers. The core objective of this thesis is to understand the ex-tent to which the urban governance of internationally displaced migrants in cities is embedded in wider structures of neoliberal and austerity urbanism, and (re)produces global structures and processes of displacement. Overall, this cumulative thesis explains that the combination of the precarious legal status of people produced in response to international displacement and through violent migration governance, and exclusionary and racialized urban migration and hous-ing policies, produce what I call multiplied displacement. Multiplied displacement describes the intersecting, overlapping, and mutually reinforcing forms, processes, experiences, and factors relevant for the (re)production of displacement against the backdrop of international displace-ment, and urban processes of marginalization, exclusion, and unhousing in cities of arrival. This thesis includes eight scholarly articles, in which I employ various perspectives and case studies to elucidate the complexities inherent in these issues across different geographical and urban contexts. Specifically, my work scrutinizes urban governance structures and their implica-tions through case studies in Europe and the United States. Central to my investigation is the revelation of the economic imperatives driving displacement, whereby multiple urban stake-holders profit from the perpetual relocation of migrants. This includes exploring the racialization processes that underpin displacement, as well as the emergence of neoliberal forms of sanctu-ary and support for displaced populations. By conceptualizing cities as both recipients and pro-ducers of displacement, this dissertation encompasses the creation of systematic knowledge about the way displacement shapes contemporary cities, how it relates to urban housing mar-kets and governance processes, and its embeddedness in wider structures of racial exclusion and marginalization in cities.

Frustrated magnetic systems are characterized by competing interactions that in some cases prevent conventional magnetic ordering, leading to unconventional ground states such as quantum and classical spin liquids. These states exhibit strong entanglement, fractional- ized excitations, and emergent topological phenomena. Such systems are of interest not only from a theoretical perspective, due to their rich and unconventional physics, but also from a materials standpoint, as they offer promising platforms for realizing exotic phases in real compounds. The theoretical study of magnetic models using numerical methods plays a crucial role in advancing our understanding of the magnetic properties of materials. It helps interpret experimental results, predicts properties not yet explored experimentally, and enhances the interpretation of data through the development of new numerical tools. In this thesis, we address these aspects through three main investigations. First, we study classical spin models on the distorted windmill lattice, which is relevant to the spin-liquid candidate PbCuTe2O6. Through this study, we determine the origin of frustration in this compound and examine the thermodynamic behavior and the magnetic excitations of the associated classical model. Additionally, by mapping out the classical phase diagram, we identify a novel type of classical spin liquid. Next, we investigate the dynamical signatures of soft modes, focusing on quartic spin oscillations in isotropic systems with spiral magnetic order. We show that these modes exhibit a gap that decreases with temperature, a feature observable in real materials through inelastic neutron scattering experiments. Finally, we introduce a machine learning–based approach to infer the underlying magnetic Hamilto- nian. Specifically, we train a neural network on synthetic spectra generated using linear spin-wave theory and apply the trained model to analyze experimental inelastic neutron scattering spectra.

Polymodal faulting, which comprises three or more coeval fault sets, has been documented from centimeter to kilometer scale in nature. Differing from previously well-known conjugate, or bimodal, fault patterns under biaxial or plane strain, the polymodal faulting phenomenon is considered to represent triaxial deformation or strain (e.g., constriction and flattening strain). Triaxial tectonic regimes can take place variably in obliquely divergent, transcurrent, and convergent settings, allowing the coeval existence of different tectonic regimes (e.g., thrust, strike-slip, and normal faulting). The classical and widely accepted Mohr-Coulomb failure criterion can predict the orientation of conjugate fault planes parallel to (i.e., contain) the direction of the intermediate stress under plane strain, whereas polymodal fault patterns forming under triaxial deformation cannot be explained with fault orientations oblique to the direction of the intermediate principal stress (σ2). Aiming to understand the evolution, geometry, and kinematics of polymodal faults, I use 3D scaled analogue and numerical modelling to generate triaxial strain fields under variable initial and boundary conditions to decode the mechanisms and mechanics of triaxial deformation. In the first step, I primarily investigate how rheology and strain rate control deformation localization, faulting regime, and pattern in brittle‐viscous crustal‐scale models under constriction strain. I perform triaxial analog experiments by varying strain rates (or extension velocity), where distributed longitudinal extension resulting in crustal thinning is accompanied by lateral shortening. I found the structural style of faults and the degree of localization as a function of strain rate. As strain rate (ė) decreases, (1) fault patterns change from conjugate sets of strike‐slip faults (ė > 3 × 10⁻⁴ s⁻¹) to sets of parallel oblique normal faults (ė = 0.3–3 × 10⁻⁴ s⁻¹) to horst‐and‐ graben system (ė < 0.3 × 10⁻⁴ s⁻¹); (2) The strain localization increases systematically and gradually. The former change in fault pattern is interpreted to be affected by the strain rate dependency of vertical coupling between the model upper crust and upper mantle, which controls spontaneous switching of principal stress axes. The latter change in strain localization is controlled by mechanical coupling between the upper and lower crust. Furthermore, many extensional systems often experience multiple phases of deformation; however, the spatial and temporal evolution of fault networks during triaxial and biaxial strain is still poorly understood. Benefiting from the first part of the work, which identifies the change in strain conditions from constriction to plane strain over strain rate, I also use a scaled analogue model to investigate fault geometry and activity across multiple phases of triaxial (constrictional) and biaxial (plane) strain by changing extension velocity to obtain time-dependent kinematic strain conditions. Our modelling results show that (1) when shifting from plane to constrictional strain, earlier developed normal faults are completely reactivated and new conjugate sets of oblique-slip faults form during the constrictional phase; (2) when shifting from constrictional to plane strain, conjugate sets of oblique-slip faults forming during constrictional strain are randomly abandoned or reactivated. New normal faults developed during plane strain cut across and link up earlier-phase faults. Kinematic interactions of fault networks between multiphase strains are identified by observing how perturbations in stress/strain domains control the geometry of new faults and mechanical obstacles hinder fault propagation. I further explore the relationship between principal stresses and polymodal fault orientation by means of 3D scaled numerical modelling. Our models demonstrate that triaxial deformation can be accommodated by the simultaneous development of faults with different trends and partitioned into one more faulting regime. Additionally, our models can explain fault distribution with respect to the principal stress. The modelling results show good similarity with the natural prototypes at various backgrounds. In regions under a constrictional deformation field, for example, Tibet, Anatolia, and the Friulian-Venetian basin, as well as in regions under a flattening strain, for example, northern Tibet and the Barents Sea, our modelling results provide new implications for fault geometry, fault kinematics, and stress distribution. Moreover, our models with multiphase triaxial and biaxial strain can re-interpret tectonic evolution in the Aegean and Barents Seas.

Racism is a structural force that organizes daily life, shapes access to resources and opportunity, and produces cumulative impacts on health across the life course. Health disparities between racially privileged and racially marginalized groups are not due to innate genetic differences; they emerge through processes that are both chronic and systematic, rooted in long-standing structures of marginalization. Despite growing recognition of racism’s health impacts, research often treats race as a static covariate and fails to interrogate racism as a dynamic, cumulative, and upstream driver of unequal health outcomes—particularly in childhood and adolescence. Few studies examine racism as a structural force that shapes mental health trajectories over time. Even fewer integrate children’s lived experiences of racialization with epigenetic data. These gaps are especially stark in Germany, where historical legacies limit the direct study of racism’s impact on development and health. This cumulative dissertation addresses these gaps by advancing and applying a race-critical biosocial framework. While biosocial approaches are well suited to explore how social conditions shape health, they have often fallen short in addressing the structural dimensions of racism. A race-critical biosocial framework offers tools to trace how racism operates and becomes embodied, shaping children’s and adolescents’ mental health. Three peer-reviewed papers structure and guide this inquiry. Paper 1 advances a race-critical biosocial framework that integrates critical race theory, developmental science, and sociogenomics, with particular attention to Germany’s scientific and sociopolitical context. Paper 2 applies this framework in the German context through communities-based qualitative research with 29 Black families. Focus group findings highlight racism as a chronic, multisite stressor that shapes family health, children’s mental health, identity development, and coping strategies. Paper 3 extends the race-critical biosocial framework to U.S. longitudinal data (N = 4,898; DNA methylation data N = 2,039), operationalizing racism through self-identified race/ethnicity, neighborhood segregation, and skin tone. Findings show that racially marginalized children exhibit higher baseline levels of internalizing and externalizing behaviors in childhood, as well as accelerated epigenetic biological aging during adolescence, with mental health and biological aging progressing in parallel. Together, the three papers provide conceptual, qualitative, and quantitative evidence that racism is a biosocial health risk. It structures children’s environments from birth, becomes embodied through stress-related mechanisms, and contributes to early mental health disparities. The dissertation highlights the urgent need for child-centered, intersectional, and longitudinal measures of racialization in both Germany and the U.S., and calls for co-designed, communities-led biosocial research. By showing how racism “gets under the skin,” it advances a race-critical biosocial agenda for public health and developmental science.

Progeroid syndromes are a heterogeneous group of rare genetic diseases characterized by a prematurely aged appearance. They are caused by pathogenic variants in various genes, including those encoding DNA repair enzymes and components of the extracellular matrix (ECM). Additionally, alterations in gene expression can also contribute to the development of these syndromes. Within the scope of this dissertation, two progeroid syndromes were characterized. First, pathogenic variants in SUPT7L were identified as the genetic cause of a new progeroid syndrome. Second, further insights into the pathomechanism of ARCL2A were obtained. One complex regulating gene expression is the transcriptional coactivator complex STAGA. Loss-of-function variants in SUPT7L, encoding a subunit of STAGA, cause a so far undescribed clinical syndrome with a progeroid appearance, developmental delay, intellectual disability and a generalized lipodystrophy. Loss of SUPT7L presumably leads to reduced stability of the entire complex, decreased expression of c-MYC- and p53-dependent genes. It also results in reduced DNA repair and subsequent accumulation of DNA damage in primary dermal fibroblasts and genome-edited HeLa cells. Moreover, evidence suggests changes of the ECM, a common feature in other progeroid syndromes such as autosomal recessive cutis laxa type 2A (ARCL2A). ARCL2A is a congenital disorder of glycosylation (CDG) characterized by connective tissue weakness and brain abnormalities. Its molecular basis are loss-of-function variants in ATP6V0A2, encoding the V0a2 subunit of the vacuolar (v)-ATPase. This subunit determines the subcellular localization of the multiprotein complex and forms the proton channel. To analyze the underlying mechanisms of ARCL2A, two mouse models were generated. A knockout (Atp6v0a2-/-) leading to absence of Atpv0a2 and a knock-in (Atp6v0a2RQ/RQ) model, carrying the p.R755Q variant, which selectively blocks proton transport. These mouse models exhibited structural aberrations of the dermis, reduced secretion of ECM proteins and altered glycosylation. However, the O-glycosylation defects appeared to be more relevant for the ARCL2A pathomechanism. Reduced O-mannosylation of ɑ-dystroglycan impairs cell-matrix interaction, leading to a secondary dystroglycanopathy involving abnormal migration of cortical neurons. Furthermore, enhanced core fucosylation in skin and murine embryonic fibroblasts (MEF) correlated with an elevated trans-Golgi pH and a delay in the intracellular vesicle transport. In both mouse models, impaired Golgi-derived acrosome formation and altered O-glycosylation lead to a globozoospermia, a previously undescribed symptom of ARCL2A. Thus, the pathomechanism of ARC2A is determined by an interplay between an elevated Golgi pH and alterations in intracellular vesicle trafficking.

Mechanosensation is a process by which nerves encode physical stimuli such as cotton swab or pinprick into electrical signals that can be understood by the nervous system. In this way, organisms can gain crucial information about the environment by means of touch sensation and avoid harmful influences thanks to nociceptive pain. But what is the molecular basis of mechanosensation, allowing this process to occur? And what happens if its functioning is disrupted? I tackle those questions in my doctoral thesis, investigating a role of newly described mechanosensitive channel and discussing tactile phenotypes in autism spectrum disorders (ASDs). This work is mostly an electrophysiological study of cutaneous mechanoreceptors, studied with the use of ex vivo mouse skin-nerve preparation. Focus is on c-fibers, small diameter unmyelinated sensory neurons, involved in relying nociceptive cues. In the first part of my doctoral project I investigate the role of Elkin1 (TMEM87a) channel in the nociceptor physiology. Results show that Elkin1-/- knockout mice exhibit lowered mechanical sensitivity when tested in behavioral assays using a hindpaw stimulation. Electron microscopy showed no structural changes in the somatosensory system of mutant animals, albeit there are changes in the physiology of sensory afferents. Extracellular recordings from single nerve fibers, made during simultaneous mechanical stimulation of receptors located in the skin, showed a changed pattern of activity in response to mechanical stimulation with faster adaptation in fibers from Elkin1-/- animals, but only when a specific protocol of stimulation was used. Furthermore, I explore the relationship of Elkin1 with Piezo2 mechanosensitive channel by studying double knockout animals. Effect of deleting both protein seem to have greater effect on dampening response to mechanical stimuli than removing any one of them separately. On the other hand, introducing human point mutation into mouse genome slightly strengthen the response. Overall, Elkin1 is a novel mechanosensory protein presumably required mostly for light touch, as changes in functioning of c-fibres point toward minor involvement in nociception. Sense of touch is also critically important for proper development. It constitutes the most primal form of communication between an infant and a parent, building foundation for more advanced social skills. Tactile-related impairments observed in toddlers pose a strong predictor of core autistic symptoms later in life and sensory processing disturbances belong to the most replicable symptoms emerging early in the diagnosis of ASDs. Modified touch perception phenotype observed in human subjects is replicated in animal models. Global knockout of 4E-BP1, the downstream effector of mTOR signalling pathway affected in some ASDs forms, was shown to be a source of mechanical hypersensitivity with enhanced nociception in mice. However, my results on the specific involvement of this phenomenon in the peripheral sensory neurons did not show any positive results. My findings, both of electrophysiological study and behavioral assessment, indicate that mechanical hypersensitivity observed in the model of 4E-BP1 deletion ca not be explained by differences in the physiology of cutaneous nociceptors.

Two-dimensional (2D) materials exhibit unique physical and chemical properties that make them promising candidates for electronic, optoelectronic, and energy-related applications. However, the limited tunability of pristine 2D materials restricts their broader practical use. This work presents a series of computational studies focused on tailoring the structural, electronic, optical, magnetic, and catalytic properties of 2D materials through functionalization and engineering strategies, including defect engineering, doping, heterostructure formation, molecular modification, and strain or pressure. The results demonstrate that these approaches effectively modulate key material properties such as band structure, charge transfer, excitonic behavior, magnetic ordering, and catalytic performance. Overall, this study provides theoretical insight and design guidelines for the rational tuning of 2D materials toward advanced device and energy applications.

This thesis focuses on the exploration of the metabolomics approach as a guided tool in the field of anti-doping by defining a workflow based on the synergy between High-Resolution Mass Spectrometry and chemometric tools.

First, the optimization of a low-energy electron ionization source to maximize the formation of molecular ion and minimize the fragmentation degree of steroid pathways, preserving the specific fragmentation pathway of the steroids considered and increasing the m/z coverage range. To this end, the effects of electron energy, emission current and source temperature on steroid fragmentation pathways were studied by performing full factorial experimental designs, using steroid reference materials chosen to cover the entire urinary steroid profile.

Second, the development and validation of systematic metabolomics workflows to reduce the time and resources required to identify direct drug metabolites for GCHRMS. To do so, the administration of 7-keto-DHEA was studied as a Proof-of-Concept to highlight the strong synergy between high-resolution mass spectrometry and chemometric tools for early detection of drug metabolites in anti-doping. A comparison of the most significant features with the spectra library validated the proposed metabolomics approach, further supported by existing data in the literature.

Third, extension of the previously proposed workflow on GCHRMS data to LCHRMS data, development and validation. The primary differences between the two workflows lie in the method validation, sample analysis processes, including preparation and acquisition, as well as in the raw data preprocessing steps. This knowledge gives the opportunity to gain insight into all possible metabolic changes, regardless of whether it is the formation of new compounds or the reduction of compounds. In contrast, the metabolite-focused approach generally reduces the scope of investigation to the formation of metabolites from the parent molecule, thus losing the response that other endogenous compounds might have as a result of its intake.

Fourth, application of the developed workflow for the investigation of the physiological and post training effects of ecdisteroid supplementation on the human serum metabolome. These outcomes elucidates the effectiveness of a metabolomics-based approach in detecting specific trends related to the intake of performance-enhancing substances that would otherwise remain undetected through traditional analytical methods or be masked by physiological changes.

The results presented in this thesis are of relevance for a more depth understanding of the complex relationships between different steroids, which may not be apparent when examining individual steroids in isolation, and in the identification of patterns or combinations of steroids that may discover new biomarkers for disease diagnosis, prognosis, or monitoring. This is a step forward in the metabolic characterization of different physio-pathological conditions that allow for the personalization of treatment strategies and optimization of individual performance outcomes. This personalized treatment enhances the value of the proposed metabolomics approach, making it beneficial not only for improving sports performance, but also in the clinical setting, where targeted supplementation can promote better health and recovery.

This dissertation has explored the development and application of black phosphorus (BP) nanomaterials through sustainable synthesis methods, aiming to unlock their potential in biomedicine and environmental remediation. The research focused on three interconnected goals: covalent functionalization of BP nanoflakes for biomedical applications, enhancement of mechanochemical synthesis for sustainable BP production, and application of mechanochemically derived BP-polyglycerol (BP-PG) nanomaterials in environmental remediation. In the first project of the thesis, a one-pot covalent functionalization method was successfully developed for exfoliated BP nanoflakes using an anionic ring-opening polymerization of glycidol. This innovative approach resulted in the formation of a BP-PG nanohybrid with high amphiphilicity, significantly enhancing its aqueous dispersibility and biocompatibility. The functionalized BP-PG demonstrated efficacy in near-infrared-responsive drug delivery against A549 lung carcinoma, MCF-7 breast cancer, and HeLa cervical cancer cell lines. These findings showcase the potential of BP-PG as a promising candidate for a broad range of biomedical applications, particularly in targeted drug delivery systems where hydrophilicity and biocompatibility are crucial. The second project addressed the challenges associated with the practical application of BP by optimizing mechanochemical synthesis methods. By modifying the ball-milling medium to enhance mass transfer and kinetic energy distribution, the research introduced a novel design that improved the efficiency of mechanosynthesis. This advancement not only reduced production costs and time but also significantly improved product quality due to the enhanced transfer of mass and reagents within the ball-mill chambers. The mechanochemical approach circumvented the need for high temperatures, toxic solvents, and complex purification steps, aligning with global sustainability efforts and providing a scalable method for producing high-quality BP essential for real-world applications. In the third project of the thesis, the mechanochemically synthesized covalently functionalized BP-PG nanomaterials were applied to environmental remediation, specifically in the recovery of precious metals like gold from simulated electronic waste leachate. This work marked the first successful mechanochemical polymerization of glycidol into polyglycerol via a "grafting-from" technique. The resulting BP-PG nanomaterial exhibited a uniform amorphous structure with a high surface area, advantageous for interfacial reactions such as gold-ion reduction. Remarkably, BP-PG achieved gold recovery capacities exceeding three times its own weight and efficiently converted gold ions into polymer-stabilized gold nanoparticles. This highlights the significant impact of nanohybrid architecture on interfacial properties and underscores the potential of mechanochemically derived BP-PG in environmental applications. Collectively, this dissertation contributes to expanding the understanding and utility of BP nanomaterials by developing sustainable and environmentally friendly synthesis methods that facilitate large-scale production. By enhancing the functional properties of BP through covalent functionalization, the research has led to improved biocompatibility and aqueous dispersibility, critical for biomedical applications. Demonstrating the versatility of BP-PG nanohybrids in targeted drug delivery and efficient recovery of precious metals showcases their potential in diverse fields ranging from medicine to environmental science. Furthermore, the pioneering of new mechanochemical techniques that can be applied to other materials and processes promotes innovation in green chemistry. This work paves the way for future advancements in sustainable material science, emphasizing the importance of designing synthesis strategies that are not only efficient but also environmentally responsible. In conclusion, the advancements presented in this dissertation lay a solid foundation for the practical application of polyglycerol functionalized BP nanomaterials. By addressing key challenges in synthesis and functionalization, and by demonstrating significant applications in biomedicine and environmental remediation, this research contributes valuable insights to the field of nanotechnology. Future work can build upon these findings to explore additional applications, optimize material properties, and further integrate BP nanomaterials into commercial technologies.

Die vorliegende Habilitationsschrift behandelt die Bedeutung des schweren Thoraxtraumas im Rahmen der Polytraumaversorgung. Von hospitalisierten Verletzten hat knapp ein Drittel Thoraxverletzungen, bei Polytraumatisierten mehr als die Hälfte der Betroffenen schwere Thoraxverletzungen, die bis zu 25% der traumaassoziierten Mortalität verursachen. Es konnte die Komplexität der viel diskutierten Notfallthorakotomie im Rahmen der Traumareanimation gezeigt werden, dass auf Basis von Fallkodierungen erfasste Diagnosen automatisiert in korrespondierende Verletzungsschweregrade umgerechnet werden können, eine verspätete Stabilisierung instabiler knöcherner Thoraxverletzungen mit einem geringeren Ausmaß an Outcome-Verbesserungen assoziiert ist, als es von einer frühzeitigen Intervention erwartet wäre, dass nicht nur die Anzahl der frakturierten Rippen, sondern ebenso die Länge der Segmentverletzungen die resultierende Thoraxwandinstabilität beeinflussen und dass ein traumatisches ARDS eine vergleichbare Mortalität mit anderen Ätiologien hat, wobei eine ECMO-Therapie situativ sicher einsetzbar sein kann.

The presented work depicts an in-depth approach on how to reach confident mass spectrometric analysis of metabolites of metandienone by gas chromatography. Metandienone is an anabolic androgenic steroid and a commonly used doping substance. Therefore, anti-doping testing strives to uncover its illicit intake by the detection of metandienone and its metabolites in athletes’ samples. In the following, the focus is mainly set on a reliable identification of the A-ring reduced metabolite structures 17ξ-methyl-5ξ-androstane-3ξ,17ξ-diol, 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol and 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-1,13-dien-3α-ol in human urine samples in parallel. First of all, the synthesis of reference material and its structural characterization built the basis of these investigations. It found application in a study of mass spectrometric fragmentation of 17α-methyl-5ξ-androstane-3ξ,17β-diol and various isotopologues and enabled fundamental understanding on underlying fragment ion formation in electron ionization mass spectrometry. Further assessment of the analytical method was supported by the latter investigations and allowed developing a method for confident identification of the targeted analytes. Therefore, only chromatographic separation of inter alia diastereomeric molecule structures made it possible to overcome the encountered challenges of indistinguishable mass spectrometric signals. In the end, proof of concept was provided by the application of this method to an administration study with metandienone. Not only did it lead to the confident identification of known and unknown excreted metabolite structures but also gave a deeper insight into the human metabolism of anabolic androgenic steroids. Concluding, besides the support to maintain confidence in anti-doping analysis of metandienone this work generally contributes to the field of bioanalytics by highlighting the importance of integral understanding of the analytical conditions. In general, chemosynthetic knowhow was used to obtain reported reference material and corresponding isotopologues. Applied analytical techniques consist of nuclear magnetic resonance experiments, gas chromatography coupled to unit mass spectrometry, high-resolution mass spectrometry, and tandem mass spectrometry.

Awareness of escalating sustainability crises, including climate change, species extinction, and growing social injustice, evokes a wide range of emotions, often negative, in a growing number of people. Worry, anxiety, sadness, frustration, and anger are frequently reported, especially by young people. Consequently, the high relevance of emotions for effective sustainability education has long been acknowledged. At the same time, emotional competencies have received too little attention in prevailing competence models. Studies from educational practice also indicate that teachers often feel unqualified to deal with emotions. The frequent suppression of emotions that results from this can demonstrably contribute to learners feeling overwhelmed by sustainability issues and avoiding them. Against this background, this dissertation examines how human emotions, sustainability crises, and education interrelate. Specifically, it examines the questions of why emotion-sensitive sustainability education is necessary and how it could be realized. In order to answer these questions, it is first necessary to examine how emotions are addressed in the German education system. The current state of research indicates that emotions are in fact too strongly neglected, despite their high relevance for all forms of learning. A mixed-methods analysis of 422 German curricula confirms this hypothesis and shows that emotional competence (with the facets of emotion knowledge, emotion recognition, emotion expression, emotion regulation, and empathy) is insufficiently structurally anchored in the German school system (Study 1). At the same time, a latent class analysis of 3,000 young people and teachers shows how widespread feelings of hopelessness are among both educators and students (Study 2). This hopelessness, along with increasingly widespread worries, fears, and frustrations, can affect mental health. Using the same sample, multiple regression analysis shows that sustainability-related emotions are significantly stronger predictors of behavior than knowledge and attitudes and thus could be central drivers of the sustainability transformation (Study 3). A systematic review then examines the role of emotions in transformative sustainability learning and derives implications for educational practice and science. The review (n = 20) reveals that widespread negative emotions (e.g., frustration, sadness, guilt) are found particularly at the beginning of transformative learning processes. In contrast, predominantly positive emotions are found during social interactions (e.g., gratitude, fun) and when trying out new actions (e.g., satisfaction, pride). This suggests how learners’ emotionality may differ substantially depending on their learning phase and the didactics chosen (Study 4). The results of the four studies and the findings of the respective strands of research highlight an asymmetry: emotions are highly relevant when people engage with sustainability issues, but at the same time the German education system in general, and sustainability education in particular, still pays too little attention to emotions. For this reason, emotional competence is proposed as a competence concept for sustainability education. Using five competence facets and concrete examples, the usefulness of the concept for sustainability education is illustrated and general recommendations for science and practice are derived.

Neurons are highly polarized cells characterized by specific structural and functional regions. The soma, or cell body, serves as a primary site for protein synthesis, while synaptic terminals located at the ends of axons are responsible for synaptic transmission. The precise transport of presynaptic proteins from the soma to these terminals is vital for the development, maturation, and maintenance of synapses. Presynaptic precursor biogenesis is a fundamental process for synaptic function and plasticity; however, its molecular mechanisms remain incompletely understood. Our research identifies Rab2 and its effector RUND1 as key regulators of presynaptic precursor vesicle (PV) formation at the trans-Golgi network (TGN). Rab2, a small GTPase, coordinates the biogenesis, sorting, and maturation of vesicles carrying presynaptic proteins essential for synaptic vesicle (SV) recycling and active zone (AZ) organization. Loss of Rab2 results in the accumulation of synaptic material— including scaffold proteins, SV proteins, and lysosomal markers—within motoneuronal cell bodies in Drosophila larval ventral nerve cords (VNCs). This mislocalization depletes presynaptic protein levels at synaptic terminals, leading to impaired neurotransmission. Electron microscopy revealed that these aggregates likely correspond to Golgi-derived transport vesicles, suggesting that Rab2 is crucial for efficient precursor export. Our RNAi-mediated screen identified RUND1 as a critical Rab2 effector that regulates presynaptic protein sorting, maturation, and trafficking. The RUN domain of RUND1 facilitates interactions with Rab2 and other regulatory proteins, including ICA69, Trabuco, and Golgin104. ICA69, a Rab2 effector, participates in secretory vesicle biogenesis and synaptic organization, while Golgin104 (CCDC186) is implicated in vesicle tethering at the TGN. Notably, the loss of RUND1produces a phenotype reminiscent of Rab2 mutants, supporting its role in the same pathway of presynaptic precursors biogenesis. Interestingly, ultrastructural analysis of vesicles in rund1−/−mutant backgrounds revealed a striking increase in elongated and tubular structures. These vesicles exhibited two distinct populations: clear and dense-core vesicles, potentially indicating a disruption in fusion or maturation processes. The presence of these heterogeneous vesicle populations suggests that RUND1 is essential for the proper segregation and functional refinement of vesicles before their transport to synaptic terminals. Overall, our findings highlight the intricate regulation of presynaptic precursor trafficking by Rab2 and RUND1, reinforcing the importance of Golgi-associated sorting mechanisms in synaptic development and function. Disruptions in this pathway impair synaptic protein localization and neurotransmission, with potential implications for understanding synaptic disorders.

Deciphering the intricate cellular interactions within the bone marrow (BM) is crucial for understanding a wide range of multifactorial diseases in immunology, regenerative medicine, and BM biology. The intricate BM microenvironment, characterized by dynamic cell trafficking, production of immune cells and self-organized remodeling, constantly shapes osteoimmunological cell functions and their metabolic adaptations. This specific microenvironment is challenging to replicate in vitro or in silico. Current intravital optical imaging techniques can investigate cells within the complex BM microenvironment but are invasive or limited in observation time, depth, hindering long term investigation of bone regeneration or specific cellular niches. This dissertation presents three novel optical imaging technologies to satisfy the critical need for long-term, minimally invasive intravital microscopy of the BM: 1) a high-energy, high-repetition-rate 3-photon (3P) laser, enabling intravital visualization of plasma cell (PC) dynamics and antibody production capacity; 2) Limbostomy, a modular microendoscope for longitudinal in vivo imaging of deep femoral BM, facilitating quantification of cellular self-organization during bone healing; and 3) FLIMB, integrating microendoscopy with NAD(P)H-dependent fluorescence lifetime imaging (FLIM), enabling label-free metabolic imaging of myeloid cells in the living BM. These methods revealed an antiproportional correlation between PC motility and antibody production capacity; the chronicity of rapid vessel sprouting and subsequent reorganization into a confined network accompanied by myeloid interactions after bone injury; and metabolic heterogeneity among myeloid cells, indicating specific metabolic patterns linked to the activation of oxidative burst and phagocytic function. These innovations provide researchers with powerful tools to study complex cellular interactions in living bone marrow, develop therapeutic strategies and monitor drug responses, for example to improve bone regeneration, combat PC dysfunction and cancer, and fundamentally understand the interplay of cellular behaviour, microenvironment and disease progression in bone marrow.

Addressing open-ended questions, the dissertation undertakes a transdisciplinary mixed-method experiment to reconstruct historical LGBT epistemic frameworks in state-socialist East Central Europe. Its aim is twofold. First, it develops new methods—combining quantitative and qualitative, evidence-based research grounded in primary sources and the critical reinterpretation of secondary sources—to recover the operations of the socialist state through an imparative (non-comparative) analytical approach. Second, it demonstrates how such decolonized perspectives enable new interpretations of queer cultural artefacts situated within socialist social, cultural, and political fields. This approach makes it possible to identify a distinctive category of LGBT artefacts within state socialism: works that were non-political, non-identitarian, and non-activist, yet profoundly queer in their epistemic and aesthetic operations. Using the uniquely transparent queer oeuvre of Soviet-Hungarian transgender artist El Kazovszkij (1948, Leningrad – 2008, Budapest) as its point of departure, the project moves between micro- and macro-levels of inquiry. Zooming in on Kazovszkij’s corpus and zooming out to the broader social and political discourses that framed and integrated it, ranging from historical political, legal and social analysis to critical hermeneutics. Grounded in art-historical inquiry, the dissertation challenges dominant Western-centric narratives of global queer history by foregrounding the specificity and complexity of state-socialist queer epistemes. It enriches non-Western histories of twentieth-century LGBT cultures and contributes to post-socialist and post-colonial studies. Through its rigorous empirical methodological experimentation, the dissertation proposes a new model for conducting research in non-Western contexts on historically ambiguous subjects - particularly in cases where empirical evidence and primary sources are opaque, uncatalogued, or difficult to access.