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Investigations into biomarkers of neuronal cell damage in autoantibody-associated psychiatric syndromes
No full textEs wird derzeit kontrovers diskutiert, ob psychiatrische Erkrankungen, welche mit neuralen Autoantikörpern assoziiert sind, zu einer neuronalen Zellschädigung führen. Daher diente die Arbeit der Beantwortung der Fragestellung, ob sich psychiatrische Patient*innen mit einem Nachweis neuraler Autoantikörper von psychiatrischen Patient*innen ohne Nachweis neuraler Autoantikörper im Muster der neuronalen Zellschädigung unterscheiden und ob sich dieses Muster vom einer Alzheimer-Krankheit differenzieren lässt.
Es wurden bei 123 Patient*innen aus der Klinik für Psychiatrie und Psychotherapie der Uni-versitätsmedizin Göttingen im Zeitraum zwischen 2017 und 2020 klinische Daten zur Psy-chopathologie, zur Kognition, zur Elektroenzephalographie und zur cranialen Magnetreso-nanztomographie, zu den neuronalen Zellschädigungsmarkern Gesamt-Tau-Protein (T-Tau), phosphoryliertes Tau-Protein 181 (pTau181), Amyloid-β-42 (Aβ42), Amyloid-β-40 (Aβ40) und Ratio Amyloid-β-42/Amyloid-β-40 (Ratio Aβ42/Aβ40) im Liquor und zu neuralen Autoantikörpern im Liquor und/oder Serum erhoben und im Vergleich zu einer Kohorte mit 27 Patient*innen mit erfüllten Kriterien einer Alzheimer-Krankheit ausgewertet. Zudem erfolgten eine Einteilung der Patient*innen in Syndrome nach dem System der Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie und eine Prüfung auf das Vorliegen einer Autoimmunenzephalitis mit Vergleich der neuronalen Zellschädigungsmarker. Es wurden je nach Fragestellung neben einer rein deskriptiven Statistik weitere unterschiedliche statistische Methoden angewandt (Kruskal-Wallis-Test, Mann-Whitney-U-Test, Chi-Quadrat-Test und einfaktorielle Varianzanalyse).
Es ist keine verstärkte neuronale Zellschädigung anhand der genannten neuronalen Zellschä-digungsmarker T-Tau, pTau181, Aβ42, Aβ40 und Ratio Aβ42/Aβ40 bei Patient*innen mit Autoantikörpern im Vergleich zu Patient*innen ohne Autoantikörper nachweisbar. Im Vergleich zur Vergleichskohorte mit erfüllten Kriterien einer Alzheimer-Krankheit unterscheidet sich die Konzentration von pTau181 im Liquor bei Patient*innen mit Serumnachweis neuraler Autoantikörper nicht. Die verschiedenen Autoantikörper-assoziierten psychiatrischen Syndrome unterscheiden sich nicht signifikant in den genannten neuronalen Zellschädigungsmarkern. Das psychoorganische Syndrom zeigt sowohl bei Patient*innen mit, als auch ohne Autoantikörpernachweis die am ehesten pathologischen neuronalen Zellschädigungsmarker im Liquor, ohne sich signifikant von den anderen psychiatrischen Syndromen zu unterscheiden. Bei Patient*innen mit möglicher und wahrscheinlicher Autoimmunenzephalitis ist keine verstärkte neuronale Zellschädigung im Liquor feststellbar.
Neuronale Zellschädigungsmarker sind differentialdiagnostisch für die Unterscheidung zwischen psychiatrischen Syndromen mit und ohne Autoantikörper nicht hilfreich. Jedoch zeigte sich eine neuroaxonale Zellschädigung bei Patient*innen mit Autoantikörper-assoziierten psychiatrischen Syndromen als ein Hinweis auf eine mögliche organische Genese. Des Weiteren ist eine neuroaxonale Zellschädigung bei Autoimmunenzephalitiden in der Literatur zwar beschrieben, lässt sich jedoch durch diese Untersuchungen nicht bestätigen. Dieses Ergebnis kann durch Unterschiede in der Kohorte mit unterschiedlichen Autoantikörperklassen und unterschiedlicher Dauer der Erkrankung erklärt werden. Weitere Studien mit anderen Zellschädigungsmarkern wie Neurofilament-Leichtketten sollten folgen, um die Art und das Ausmaß der neuronalen Zellschädigung bei Autoantikörper-assoziierten psychiatrischen Erkrankungen besser beurteilen zu können.There is currently controversy surrounding whether psychiatric disorders associated with neural autoantibodies lead to neuronal cell damage. Therefore, the aim of this study was to answer the question of whether psychiatric patients with evidence of neural autoantibodies differ from psychiatric patients without evidence of neural autoantibodies in terms of the pattern of neuronal cell damage and whether this pattern can be differentiated from that of Alzheimer's disease.
Clinical data on psychopathology, cognition, electroencephalography, and cranial magnetic resonance imaging, as well as on the neuronal cell damage markers total tau protein (T-Tau) and tau-phosphorylated protein 181 (pTau181), were collected from 123 patients from the Department of Psychiatry and Psychotherapy at the Universitätsmedizin Göttingen between 2017 and 2020. pathology, cognition, electroencephalography, and cranial magnetic resonance imaging, as well as on the neuronal cell damage markers total tau protein (T-Tau), phosphorylated tau protein 181 (pTau181), amyloid-β-42 (Aβ42), amyloid-β-40 (Aβ40), and the ratio of amyloid-β-42 to amyloid-β-40 (ratio Aβ42/Aβ40) in cerebrospinal fluid, as well as neural autoantibodies in cerebrospinal fluid and/or serum, were collected and evaluated in comparison to a cohort of 27 patients who met the criteria for Alzheimer's disease.
In addition, patients were classified into syndromes according to the system of the Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie and tested for the presence of autoimmune encephalitis by comparing neuronal cell damage markers. Depending on the question being addressed, various statistical methods were used in addition to purely descriptive statistics (Kruskal-Wallis test, Mann-Whitney U test, chi-square test, and one-way Analysis of Variance).
No increased neuronal cell damage is detectable based on the aforementioned neuronal cell damage markers T-Tau, pTau181, Aβ42, Aβ40 and ratio Aβ42/Aβ40 in patients with autoantibodies compared to patients without autoantibodies. Compared to the control cohort that met the criteria for Alzheimer's disease, the concentration of pTau181 in the cerebrospinal fluid does not differ in patients with serum evidence of neural autoantibodies. The various autoantibody-associated psychiatric syndromes do not differ significantly in the aforementioned neuronal cell damage markers. The psychoorganic syndrome shows the most pathological neuronal cell damage markers in the CSF in both patients with and without autoantibody detection, without differing significantly from the other psychiatric syndromes.
In patients with possible and probable autoimmune encephalitis, no increased neuronal cell damage can be detected in the cerebrospinal fluid. Neuronal cell damage markers are not helpful in the differential diagnosis for distinguishing between psychiatric syndromes with and without autoantibodies. However, neuroaxonal cell damage in patients with autoantibody-associated psychiatric syndromes was found to be an indication of a possible organic origin. Furthermore, although neuroaxonal cell damage in autoimmune encephalitis has been described in the literature, it cannot be confirmed by these studies. This result can be explained by differences in the cohort with different autoantibody classes and different durations of the disease. Further studies with other cell damage markers such as neurofilament light chains should follow in order to better assess the nature and extent of neuronal cell damage in autoantibody-associated psychiatric disorders.2025-12-1
Bringing bioinformatics to the bench: SubtiWiki 5.0 and new web tools for research
No full textModellorganismen spielen in der biologischen Forschung eine zentrale Rolle, da ihre Untersuchung
wichtige Einblicke in fundamentale Prozesse des Lebens gewährt und die Entwicklung
biotechnologischer Verfahren befördert. Die intensive Erforschung dieser Organismen erstreckt sich
von biochemischen und genetischen Studien über großangelegte Systemanalysen bis hin zu
computergestützten Vorhersagen. Datenbanken organisieren diese Fülle an Informationen in
übersichtlicher Weise, um die Entwicklung neuer Forschungshypothesen zu unterstützen. SubtiWiki
ist eine prominente Datenbank für Bacillus subtilis, den Modellorganismus für Gram-positive
Bakterien. Sie enthält sowohl kuratierte Informationen und Datensätze aus Publikationen als auch
interaktive Funktionen für die intuitive Analyse. Um mit der aktuellen Forschung mitzuhalten, ist eine
kontinuierliche Verbesserung des Frameworks und Erweiterung der Funktionalität nötig. So hat vor
kurzem etwa die Entwicklung von AlphaFold die akkurate Vorhersage von Proteinstrukturen
ermöglicht, womit völlig neue Wege der strukturbasierten Analyse eröTnet wurden. In dieser Arbeit
hat SubtiWiki ein vollständig neues Software-Fundament erhalten (Version 5.0), welches auf
modernen Frameworks aufbaut. Die Plattform enthält zudem viele neue Funktionen, wie die
interaktive Visualisierung von Gennachbarschaften und Proteinstrukturen sowie der Wirkung von
Mutationen. Außerdem haben Metaboliten eigene Seiten erhalten, auf denen ihre Rolle im
StoTwechsel detailliert dargestellt wird. AlphaFold und verwandte Werkzeuge bergen zwar immense
Möglichkeiten, sind aber für Experimentalwissenschaftler nicht immer leicht zugänglich. Um diese
aktuellen Entwicklungen in der computergestützten Strukturbiologie ins Labor zu bringen, wurde
Foldseek in SubtiWiki integriert. Dieses Analysetool für Strukturähnlichkeiten kann selbst entfernte
evolutionäre Beziehungen zwischen Proteinen identifizieren, die durch einen Sequenzvergleich nicht
gefunden werden. Zudem wurden die Ergebnisse einer Proteomstudie zu B. subtilis eingepflegt, in
der Protein-Protein-Interaktionen experimentell ermittelt und in silico per AlphaFold-Multimer
modelliert wurden. Um die Evaluation solcher Strukturvorhersagen zu vereinfachen, wurde
außerdem der PAE-Viewer entwickelt. Dieses Webtool ermöglicht die Bewertung von multimeren
AlphaFold-Vorhersagen, und unterstützt darüber hinaus die experimentelle Validierung durch die
Darstellung von Crosslinks. Mit den hier implementierten Änderungen am Framework und
Erweiterungen im Informationsgehalt steigert SubtiWiki seinen Nutzen für die B. subtilis-Community
signifikant und bietet neue Werkzeuge für die Beantwortung von Forschungsfragen. Die innovativen
Funktionen, die in die Plattform integriert wurden, dürften dabei helfen, die neuesten Fortschritte der
computergestützten Strukturbiologie ins Labor zu bringen.Model organisms are central to biological research, as their study provides crucial insights into fundamental processes of life and enables biotechnological applications. The intensive research on these organisms spans multiple disciplines from biochemical and genetic studies to large-scale omics analyses and computational predictions. To organize this wealth of information and to aid scientists in the development of novel research hypotheses, model organism databases integrate and present data in a comprehensive manner. Bacillus subtilis, the model organism for Gram-positive bacteria, is the most studied prokaryote next to Escherichia coli. SubtiWiki is a B. subtilis database that was first released in 2009. It contains a large body of expert-curated content, datasets from relevant studies, and interactive features for the intuitive exploration of data. As new data and tools are being released, continuous improvement of the framework is necessary to stay up to date with ongoing research. Recently, the introduction of AlphaFold and related tools has revolutionized biological research, as the accurate prediction of protein structures has opened up a world of structure-based analysis. In this work, SubtiWiki has received a completely new foundation (version 5.0), which builds upon modern, state-of-the-art frameworks and includes many new features, such as an interactive display for gene neighborhood conservation, integration of metabolite data, a mutant fitness graph, and a 3D protein structure viewer. AlphaFold and related resources offer great opportunities but are not always easily accessible to lab scientists. To keep up with these latest developments in computational structural biology, Foldseek, a structure similarity analysis tool, was integrated, which allows identification of remote evolutionary relationships between proteins that cannot be detected by sequence comparison alone. Moreover, the results of a proteome-level B. subtilis study were incorporated, where protein-protein interactions were experimentally identified and computationally modelled with AlphaFold-Multimer. To facilitate the evaluation of such predictions, the PAE Viewer was developed. This web tool allows for the assessment of multimeric AlphaFold predictions and also supports experimental validation through the display of crosslinks. In addition, the framework of SubtiWiki was applied to two additional bacteria to provide the respective scientific communities with extensive resources for research: MycoWiki for Mycoplasma pneumoniae, and ListiWiki for Listeria monocytogenes. With these changes, SubtiWiki provides the B. subtilis community with substantially improved utility and new tools to approach research questions. The cutting-edge features incorporated into the platform may help to bring the latest advances in computational structural biology to the lab.2025-11-0
Morphological and functional consequences of an AAV-mediated Foxo3 knockdown on C2C12 myoblasts
No full textSarkopenie ist eine häufige Erkrankung bei älteren und hospitalisierten Patienten. Sie führt zu einem erhöhten Risiko für Stürze und Hospitalisierung, was wiederum zu höheren Gesundheitskosten und einer deutlichen Einschränkung der Lebensqualität führt. Die derzeitigen Therapieansätze, die hauptsächlich auf körperlicher Aktivität und ernährungsphysiologischer Unterstützung basieren, sind bei hospitalisierten Patienten eingeschränkt, was die Notwendigkeit neuer Behandlungsansätze unterstreicht.
Vor diesem Hintergrund spielt der Transkriptionsfaktor Foxo3 eine zentrale Rolle, da er unter anabolen Bedingungen inaktiviert wird, während er unter katabolen Bedingungen die Expression der muskelspezifischen Ubiquitin-Ligase Fbxo32 induziert, die den Proteinabbau antreibt. Die Hypothese war, dass ein AAV-vermittelter, langfristiger Foxo3-Knockdown in C2C12 Myoblasten zu niedrigeren Fbxo32-Spiegeln führt, was wiederum zu einer verbesserten Morphologie und Funktion führt. Eine in silico Analyse zeigte eine erhöhte Foxo3-Expression bei gealterten Mäusen, und die am unterschiedlichsten exprimierten Gene standen in Zusammenhang mit menschlichen Muskelatrophieerkrankungen. Um ein myogenes Differenzierungsmodell in vitro zu etablieren, wurden C2C12 Wildtypzellen mit AAV2-Vektoren transduziert, die entweder ein Kontrollplasmid oder Foxo3-spezifische siRNAs enthielten. Die transduzierten Zellen wurden mittels FACS selektiert, um mono- und polyklonale Zelllinien zu erzeugen, wobei siControl K8 und siFoxo3 K2 aufgrund vergleichbarer Wachstumseigenschaften für die weiteren Experimente ausgewählt wurden. Anschließend wurden diese über 9 Tage zu Myotuben differenziert. In den folgenden Experimenten konnte ab Tag 3 ein stabiler und langfristiger FOXO3-Knockdown auf Proteinebene nachgewiesen werden. Die morphologische Analyse zeigte eine verzögerte Differenzierung, die zur Bildung kleinerer und weniger fusionierter Myotuben führte. Diese Ergebnisse spiegelten sich auch in der funktionellen Analyse wider. Myotuben mit Foxo3-Knockdown zeigten eine verlängerte Zeit bis zum Kontraktionsmaximum, sowie eine verlängerte Kontraktionsdauer. Mechanistisch führte der FOXO3-Knockdown auf Proteinebene zu einer kompensatorischen Hochregulation von Foxo1, das ebenfalls die Expression von Fbxo32 förderte. FOXO3 spielt zudem eine Rolle bei der Regulation der Myod1-Expression, die in frühen Differenzierungsphasen entscheidend ist, sowie bei der Aufrechterhaltung der zellulären Integrität. Der Knockdown von FOXO3 führte zu DNA-Doppelstrangbrüchen, was die Hochregulation von Atm und nachfolgend Tp53 offenbarte. Tp53 ist ein Induktor der Foxo3-Expression und hemmt die Expression von Myog, welches in späteren Differenzierungsphasen für die Myoblastenfusion entscheident ist.
Zusammenfassend konnte die initiale Hypothese widerlegt werden. Der AAV2-vermittelte langfristige FOXO3-Knockdown vor Beginn der Differenzierung hemmte sowohl die Initiation der Differenzierung, als auch die spätere Myoblastenfusionin Abhängigkeit von Atm- und Tp53-Expression.Sarcopenia is a common disease in the elderly and hospitalized population, leading to a higher risk of falling and hospitalization, resulting in increased healthcare costs and significantly reduced quality of life. Current therapies, mainly based on physical activity and nutritional support, are limited in hospitalized patients, highlighting the need for novel approaches.
With that background, the transcription factor Foxo3 plays a pivotal role, as it is inactivated in anabolic situations, whereas in catabolic situations, Foxo3 expresses the muscle-specific ubiquitin ligase Fbox32, driving protein degradation. The hypothesis is that an AAV-mediated long-term Foxo3 knockdown in C2C12 myoblasts results in lower levels of Fbxo32, which in turn leads to an enhanced morphology and function. An in silico analysis revealed elevated Foxo3 expression in aged mice and the most differentially expressed genes were associated with human muscle atrophy diseases. To establish a myogenic differentiation model in vitro, C2C12 wild-type cells were transduced with AAV2 vectors carrying a plasmid for either control or Foxo3-targeting siRNAs. Transduced cells were selected by FACS to generate mono- and polyclonal lines, with siControl K8 and siFoxo3 K2 chosen for further experiments based on comparable growth characteristics. They were further differentiated into myotubes for 9 days. In the subsequent experiment, a successful, stable and long-term FOXO3 knockdown at protein level was confirmed from day 3 onwards. The morphological analysis demonstrated a delayed differentiation, leading to the formation of smaller and less fused myotubes due to the Foxo3 knockdown. These results were reflected in the functional evaluation. Here, the Foxo3 knockdown myotubes exhibited a longer time to peak and longer contraction duration. Mechanistically, as a consequence of the FOXO3 knockdown at the protein level, there is a compensatory upregulation of Foxo1, which also expresses the Fbox32. FOXO3 plays a role in the regulation of Myod1 expression, which is crucial during early differentiation. Foxo3 plays a crucial role in maintaining cellular integrity. Consequently, the FOXO3 knockdown at the protein level results in DNA double-strand breaks, as indicated by an upregulation of Atm and further Tp53 expression. Tp53 is a driver of Foxo3 expression and inhibits the Myog expression, which is crucial for myoblast fusion in later differentiation.
In conclusion, the initial hypothesis was falsified. The AAV2-mediated long-term FOXO3 knockdown prior to differentiation inhibited its own initiation of differentiation and further inhibited its later differentiation with myoblast fusion depending on Atm and Tp53 expression2025-12-1
Responses of timber species to climatic changes in Northern Germany: Studies on the radial stem growth and the fine root system of European beech, Sessile oak, Scots pine and Douglas fir along a gradient of increasing aridity
No full textClimate change with rapid warming and increasing atmospheric and edaphic drought exposes trees and forests to growing stress. Most of Central Europe’s economically important tree species have suffered vitality losses, growth decline and locally increased mortality during recent hot droughts. Foresters thus require comparative assessments of the major timber species’ climate vulnerability.
This thesis consists of two field studies from the disciplines of dendro- and root ecology to compare the drought response of the major timber species European beech (Fagus sylvatica L.), sessile oak (Quercus petraea (Matt.) Liebl.), Scots pine (Pinus slyvestris L.) and Douglas fir (Pseudotsuga menziesii (Mirb.) Franco) along a precipitation gradient (834 − 570 mm yr-1). The study sites were located in mature, monospecific forest stands in the lowlands of Northern Germany on deep sandy to sandy-loamy soils. The aim of the thesis was to explore the four species’ climate vulnerability, assess their adaptive potential to reduced precipitation and to expand the knowledge about the species’ response to increasing climatic aridity. The overarching goal in combining the two studies was to facilitate cultivation decisions for policy makers and forest managers.
Temperate trees preserve information on secondary growth constraints within the distinct pattern of their tree rings. To assess a tree species’ response to climatic stress, dendroecology uses wood increment cores as natural archives to analyze past growth patterns under variable climatic conditions. The dendroecological study in the thesis at hand compared long-term radial growth trends (basal area increment; BAI) and climate-growth relationships along the gradient and explored growth patterns at the stand level (growth synchrony). Two wood increment cores per tree were taken in early spring of 2021 from 20 (co-)dominant trees on each of the five sites per species, for a total of 400 sampled trees. The results show that the BAI of Douglas fir and beech had decreased in recent decades at most sites, while pine and oak growth was predominantly stable or had even increased. Yet, the growth synchrony of all species had increased at most stands over the past decades, indicating an increase of climatic stress. Increasing BAI of oak and pine at drier sites may indicate successful acclimation of these species to reduced precipitation. The conifers profited primarily from sufficient moisture in late-summer and higher temperature in February and March, the broadleaf trees from a moister and cooler previous-year summer. Winter temperature emerged as an important new driver of growth in pine, Douglas fir and oak, which may promote the growth of these species at some sites through reduced winter cold stress.
While there is already extensive research addressing aboveground traits, less is known about the drought resistance and drought response of the trees’ fine root system, the site of water and nutrient uptake. The root ecological field study therefore comprised two separate sampling methods on the fine root system and its productivity with the aim to explore potential acclimatization to water scarcity and providing a comprehensive understanding of the drought response of this most vital part of the plants. A fine root inventory was carried out in autumn of 2021 after a relatively moist summer to assess fine root dynamics as well as morphological and chemical traits. An in-growth core field experiment in the subsequent year yielded data on fine root productivity and turnover rate. For each target species, fine root biomass (FRB), productivity (FRP), lifespan, and morphological traits were studied and the response to mean annual precipitation across sites was modelled. FRB increased in beech toward drier sites, decreased slightly in oak, and remained unchanged in pine and Douglas fir. FRP increased in beech and Douglas fir with drier conditions, but remained stable in oak and pine. All species exhibited increased root tissue density under drought, but only conifers showed a consistent shift to more conservative traits, reflected in longer root lifespan under reduced precipitation. The study revealed diverse belowground drought responses among the species, including altered fine root dynamics and morphological adjustments, indicating multiple resilience strategies. Root trait modifications, although minor, were complex, species-specific, and influenced by phylogeny, underscoring the need for further field studies and refined models to better understand belowground drought responses.
Both studies and a literature evaluation led to the conclusion that all four species, but especially Douglas fir and beech, are increasingly negatively affected by the drier summers the study region and seem vulnerable to climate warming in the North German Lowlands. Oak and pine showed a successful drought strategy under increasingly warmer and drier conditions, when they are acclimated to drier conditions. Although oak was assessed as the most drought tolerant species, there were indications that oak’s specific drought response may cause increased vulnerability to both abiotic and biotic agents in a future with a higher drought frequency, if imbalances in the trees carbon budget arise. Thus, forest management were advised to increasingly consider other minor timber species for silvicultural decisions.2025-12-2
Theory of Chromosomal Crossover Placement
No full textChromosomes encode genetic information in living organisms. In species that reproduce sexually, each cell contains a maternal and a paternal copy of each homologous chromosome. During meiosis, a special type of cell division of germ cells, homologous chromosomes pair up and exchange genetic material in a process called crossover. Chromosomal crossovers are crucial for ensuring the proper segregation of chromosomes during meiosis and increasing genetic variability. Experimentally, it is well established across most species that the number of crossovers per chromosome is typically small, but at least one, a phenomenon known as crossover assurance. Furthermore, crossovers are subject to interference, whereby multiple crossovers on the same chromosome are more widely spaced than would be expected by chance. In other words, small distances between crossovers are inhibited. A recently proposed coarsening model, similar to Ostwald ripening, explains these observations. Specifically, the model posits that, in an early meiotic stage, small droplets of the HEI10 protein form along the chromosome and exchange proteins through diffusion along the synaptonemal complex, a structure that physically connects the chromosomes along their axes. Larger droplets grow at the expense of smaller ones until only a few large droplets remain. These large droplets ultimately determine the placement of crossovers. Consequently, the model predicts crossover assurance and interference because the diffusion along the axes inhibits nearby droplets and ensures that at least one droplet remains per chromosome. The model also predicts an increased crossover count for mutants with elevated HEI10 levels, which is consistent with experimental data. However, current models cannot comprehensively explain observations of mutants that still form HEI10 droplets that co-localize with crossovers while lacking the synaptonemal complex. In this case, HEI10 will likely be exchanged via the surrounding nucleoplasm, suggesting that the spatial positions of the droplets no longer affect their behavior, thereby abolishing interference.
The primary objective of this thesis is to contribute to a deeper understanding of the biophysical mechanisms underlying crossover placement. First, we provide and develop tools to quantitatively analyze experimental and numerical crossover data. In particular, we introduce a novel quantification of interference: the interference length, which captures known aspects and unveils a similarity of interference across species, hinting at a common mechanism. Next, we develop an extended coarsening model that considers HEI10 exchanges along the synaptonemal complex and through the nucleoplasm in a thermodynamically consistent manner. The model coherently explains experimental data from Arabidopsis mutants. We extensively investigate the model and derive analytical scaling relations for the number and size of droplets. This allows for simple, quantitative analyses across species and mutants. Furthermore, we numerically analyze the effect of nucleoplasmic exchange on the behavior of the wild type when both types of exchange are present. Our results show that a significant portion of exchange may be mediated by the nucleoplasm while maintaining crossover assurance and interference. However, the coarsening model does not yet capture the initial stage. To address this, we present a new model of early droplet formation. This model assumes that HEI10, or some other related protein, first wets the synaptonemal complex with a thin film, and then breaks apart into separate droplets due to Rayleigh-Plateau instability. Early numerical investigations are consistent with experimental data. Taken together, the analytical tools and the extended coarsening model provide a solid framework for further investigating the mechanisms determining crossover placement.2026-01-2
Ecophysiological characterization and modelling of macadamia orchards in Limpopo, South Africa
No full textMacadamia is a high-value tree nut crop experiencing a global rise in demand. South Africa is the world’s largest producer, and macadamia orchards are rapidly expanding across the country. However, this expansion is linked to increased irrigation water use in a water-scarce region, already facing challenges from unsustainable freshwater withdrawals, partly driven by population growth, and exacerbated by the impact of climate change. Therefore, enhancing irrigation water use efficiency (IWUE - here defined as crop yield per unit of irrigation water used) is critical for sustainable macadamia production. This can be achieved through two complementary strategies: (i) sustainably increasing yields by targeting and reducing yield-limiting factors, and (ii) reducing water consumption by optimizing irrigation management and minimizing unproductive water loss.
This thesis explores both approaches to enhance IWUE of macadamia orchards employing a combination of methods and techniques, including literature reviews, expert interviews, analyses of historical climatic and production data, a comprehensive field experimental and environmental monitoring campaign, and ecophysiological modelling. The field experiments and monitoring systems were established and conducted over two years on two farms (in total four macadamia orchards) in Levubu, South Africa. This included continuous data collection on tree transpiration, microclimate, and soil water content, alongside periodic monitoring of tree morphology and phenology. These data were analyzed to gain deeper understanding of macadamia water use behavior and were used to calibrate and validate a novel macadamia transpiration model, enabling the upscaling of findings from field-level to broader cultivation regions and diverse climatic conditions.
Chapter I provides a general introduction to the topic, objectives, methodology, and the structure of this thesis.
Chapter II reviews sustainable management practices to mitigate the impacts of agricultural intensification under climate change. These include adopting water-saving irrigation systems, reducing irrigation to precisely meet the trees’ specific water requirements, and integrating technological innovations (e.g. soil moisture probes and remote sensing) along with water-saving practices (e.g. mulching) to reduce the water footprint of macadamia orchards.
Chapter III investigates strategies to sustainably increase the productivity (i.e. nut yield) of macadamia orchards. In particular, it analyzes the effects of orchard characteristics and environmental factors on historical yields (2010-2021) from 247 orchards along an altitudinal gradient (600 to 950 m a.s.l.) in Levubu, using mixed-effects models. The study also evaluates the role of irrigation in counteracting abiotic stresses (i.e. heat and drought) on productivity. Results show highly variable yields (from 1.2 to 4.0 tons dry nut-in-shell per hectare) and a declining trend in productivity, driven by alternating bearing patterns and increasingly adverse climatic conditions. Key climatic factors affecting yields included high temperatures and low global radiation during nut development, as well as insufficient rainfall during the dry season. Orchard characteristics such as cultivar, elevation, planting density, and tree age also significantly influenced productivity. While irrigation increased yields, it did not fully counteract climatic stress, emphasizing the need for integrated solutions combining improved orchard management and genetic advancements to sustainably enhance macadamia productivity and climate resilience.
Chapter IV examines macadamia water use behavior, focusing on daily water use and transpiration patterns across seasons, cultivars, and tree age classes, while identifying the key drivers of tree transpiration. Full-bearing trees transpired between 0.7 and 1.1 mm per day during dry and rainy seasons, respectively – which is lower than assumed by current industry standards (on average 2.0 mm per day). This suggests that orchards are very likely over-irrigated. Macadamia trees in our study orchards exhibited a predominantly conservative (isohydric) water use strategy, characterized by strict stomatal control. Different cultivars displayed varying water use behavior. Such plasticity in water response behavior has implications for both macadamia tree productivity and climate resilience. Transpiration was driven by microclimatic factors, with a vapor pressure deficit threshold of 1.5–2.0 kPa limiting stomatal conductance, regardless of soil water availability. Thus, increasing irrigation under high evaporative demand does likely not enhance tree transpiration but instead risks leading to over-irrigation and reduced IWUE.
Ecophysiological modelling approaches provide valuable tools for complementing and upscaling the field-level results from Chapter IV and other similar studies on macadamia tree water requirements. In Chapter V, a simple, process-based model designed to simulate tree transpiration under non-limiting water conditions with minimal data requirements was adopted and evaluated for macadamia trees. The model was further developed to simulate transpiration under water deficit conditions, accounting for the variability in water availability commonly found in southern Africa. The model’s satisfactory performance suggests that it could serve as a valuable tool for optimizing irrigation practices and conserving water resources in macadamia orchards.
The final chapter VI discusses and evaluates the two proposed pathways for enhancing IWUE in macadamia orchards, with a particular focus on the implications of climate change, and addressing socioeconomic aspects related to water costs and allocations, as well as nut prices and global trends of the macadamia industry. Based on the findings of this thesis, a major recommendation to practitioners and policy makers is to prioritize the reduction of irrigation water use, potentially through the adoption of promising strategies such as regulated deficit irrigation.2026-02-0
Elastic deformation of thin glass by excimer-laser-induced stress modification
No full textExcimer laser irradiation of borosilicate glass enables precise surface modification through
both ablation and stress engineering. This becomes particularly important in the field
of high-precision optics, especially for thin mirrors, such as those used in X-ray telescopes,
which are highly sensitive to stress-induced deformations. In this work, I
demonstrate that spatially homogeneous irradiation with an ArF excimer laser ( =
193 nm) induces tensile stress by forming a stress-bearing melt layer, resulting in parabolic
substrate deformation analogous to thin-film-induced bending. The deformed area is
confined to the lateral extent of the irradiation pattern, with curvature magnitude determined
by the areal coverage, melt layer thickness and stress. This bending behaviour is
attributed to the temperature gradient mechanism (TGM), where a laser-induced steep
temperature gradient near the surface causes plastic deformation. Upon cooling, the
contraction of the upper surface layers result in tensile stress.
I show that patterned irradiation introduces anisotropic stress components, enabling
distinct deformation modes such as uniaxial bending. A structural mechanics model
is developed that incorporates insights from ns-laser-induced material modifications
and ablation dynamics. The presented model is validated through finite element simulations,
which closely reproduce the experimentally observed anisotropic bending behaviour.
The ability to decouple curvature along principal directions offers enhanced flexibility
for figure correction. To demonstrate this, correction schemes using both homogeneous
and patterned irradiation are developed and applied to thin glass sheets with functional
layers, such as reflective chromium films. The resulting surface profiles are analyzed
and compared to evaluate the effectiveness of each approach.
Since the laser-based approach is limited to the introduction of tensile stress, a complementary
method is investigated using compressively stressed substoichiometric SiO
(1 ≤ ≤ 2) deposited at elevated pressures. The resulting film stress is tunable via
the deposition conditions and the films´ ablation behaviour under ArF excimer laser
irradiation is characterized. By selectively ablating these coatings, localized stress relief
can be achieved. Proof-of-principle experiments demonstrate the potential of this
method for figure correction of optics with compressively stressed coatings.
Together, these two approaches, laser-induced tensile stress and patternable compressive
stress relief, broaden the toolbox for high-precision figure correction of optical
components and pave the way for future fabrication of freeform optics.2026-02-0
Vergleich der Wurzelkanalpräparation an echten Zähnen im Vergleich zu 3D-gedruckten Zähnen: eine Mikro-CT-Studie
Get PDFObjective: The aim of this study was to evaluate the suitability of three-dimensionally printed teeth for endodontic education by comparing them with natural teeth.
Methods: Using micro-computed tomography (µCT) and three-dimensional printing, replicas of natural teeth were created. Standardized root canal treatments were performed on both the natural teeth and their corresponding replicas following the same preparation protocol. Pre- and post-treatment µCT scans were used to assess differences in the volume and surface area of the prepared root canals. Additionally, the Hausdorff distance was measured, and visual comparisons of the canal morphology were conducted.
Results: Statistical analysis revealed significant differences in the volume of distal canals and the surface area of mesiolingual canals between natural teeth and their printed replicas. However, no significant differences were found in the Hausdorff distance, suggesting similarity in the overall canal morphology. Despite this, graphical analysis indicated notable deviations in certain cases.
Conclusion: Three-dimensional printing offers promising potential for endodontic education by providing standardized conditions for training and assessment. It also facilitates comparative studies of different file systems and preparation techniques. However, further research is required to refine material properties and data processing methods. While current models may be suitable for specific applications, their unrestricted use in education and research remains limited. Continued advancements in material science and printing technology will be necessary before broader implementation can be recommended.2025-04-2
Tau-Protein im Liquor cerebrospinalis in der Differenzialdiagnostik bei Morbus Alzheimer und sporadischer Creutzfeldt- Jakob-Krankheit
No full textIn der Diagnostik der Alzheimer-Demenz (AD) hat sich das totale Tau (t-Tau) im Liquor als
ein wichtiges diagnostisches Mittel etabliert. Allerdings wurden auch bei Patient*innen mit
Creutzfeldt-Jakob-Krankheit (CJK) stark erhöhte t-Tau-Werte gefunden, welche die
Unterscheidung beider Erkrankungen anhand dieses Markers erschweren. In dieser Studie
wurde die diagnostische Genauigkeit des t-Taus und der t-Tau/phosphoryliertes Tau-Ratio
(t-Tau/p-Tau-Ratio) zur Unterscheidung von CJK und Alzheimer-Demenz, vor allem in
Bezug auf verschiedene Subgruppen (unter anderem die rapid-progressive Alzheimer-
Demenz (rpAD)) untersucht. Zusätzlich wurden hohe t-Tau-Werte und ihre assoziierten
Diagnosen in einer nicht selektierten Laborkohorte untersucht.
Um oben genannte Fragestellung zu untersuchen, wurden in einer retrospektiven Studie bei
310 Patient*innen mit sCJD (n=205), non-rpAD (n=65) und rpAD (n=40), t-Tau-
,
phosphoryliertes Tau- und t-Tau/p-Tau-Ratio-Werte im Liquor untersucht. Die
diagnostische Genauigkeit der verschiedenen Marker wurde berechnet und verglichen. Des
Weiteren wurden die Differenzialdiagnosen für alle Patient*innen eines neurochemischen
Labors mit t-Tau > 1250 pg/ml im Liquor ermittelt (n=199 von 7036 Patient*innen).
Das t-Tau zeigte bei der Unterscheidung zwischen CJK und AD eine AUC von 0,942,
während die AUC bei der Unterscheidung zwischen CJK und rpAD 0,918 betrug. Die Ratio
zeigte signifikant höhere AUCs (p < 0,001) von 0,992 (CJK vs. AD), bzw. 0,990 (CJK vs.
rpAD). In der Kohorte des neurochemischen Labors machten Prionerkrankungen mit 25%
den größten Anteil aus, wobei auch nicht-neurodegenerative Erkrankungen hohe t-Tau-
Werte zeigten.
Das t-Tau im Liquor scheint ein zuverlässiger Biomarker in der Diagnostik der CJK zu sein,
allerdings können falsch-positive Werte auftauchen, vor allem bei rpAD und akuten
Enzephalitiden. Die t-Tau/p-Tau-Ratio kann womöglich bei der Differenzierung von CJK
und rpAD in Zentren, in denen spezifischere Biomarker nicht zur Verfügung stehen, von
Vorteil sein.2025-07-0
Dendroclimatic investigation of European beech growth dynamics along a precipitation gradient in northern Germany
Get PDFThis thorough study of European beech (Fagus sylvatica) growth limits in Northern Germany shows the major difficulties caused by climate change and global warming. Drawing on the findings of three main chapters, we arrive at several significant conclusions on the elements affecting the beech growth surface: rising temperatures, changing precipitation patterns, drought, and the increasing influence of extreme weather events.
Rising Temperatures and Heat Stress: European beech is particularly vulnerable to rising temperatures in important growth months, including April, June, and September. Heat stress in beech populations has grown as the number of hot days with temperatures above 30 °C rises dramatically since the 1980s (Chapter 4). Summer's higher vapor pressure deficits (VPD) lower stomatal conductance, so restricting photosynthesis and growth. Although warming has lengthened the Growing Season Length (GSL), the higher frequency of heat stress offsets the advantage of a longer season. Extended GSL over 150 days has produced a minimal increase in growth, especially in drier areas; rather, it has caused further decreases due to continuous heat stress (Chapter 4). This shows how, whereas a longer growing season used to foster growth, it is now causing stress-induced decreases in growth.
Another major limitation for European beech is drought sensitivity and water stress. The trees are highly dependent on water availability during the summer, especially in June, when maximum stem development occurs. In places where growing season precipitation is less than 360 mm, European beech falls dramatically (Chapter 3). The combination of low precipitation and a declining climatic water balance (CWB) intensifies water stress, particularly during the months of April and June (Chapter 2). A negative CWB causes water shortage, hydraulic failure, and carbon hunger—where evapotranspiration exceeds precipitation. Particularly in the southeast and drier areas of Northern Germany, where water limitations are more clear-cut, these processes reduce growth and increase death rates.
The declining CWB has mostly affected the drier parts of Northern Germany, resulting in increased squeezing of beech populations. While water balance varies somewhat in some coastal regions, most inland and southeast places have a negative CWB, which increases drought stress (Chapter 2). This negative water balance prevents beech trees from receiving enough moisture, causing harm to their physiological processes and increasing their chances of growth reduction and death.
Soil conditions and stand structure greatly affect European beech's sensitivity to drought and stress brought on by climate change. Drought-induced growth decreases are more likely in beech populations that thrive on sandy soils with low water retention capacity (Chapter 3). Similarly, drought exacerbates the competition for nutrients and water in deep forests with high tree density. Researchers have demonstrated that thinning, a common forest management technique, lessens these effects by lowering competition and increasing resource availability, thereby strengthening beech tree resilience during dry times (Chapter 3). This emphasizes the need for controlling stand density and enhancing soil conditions to allow beech plants to withstand future environmental challenges.
Regional Growth Declines: Climate change causes variations in European beech growth over Northern Germany. Drier and more continental sites are experiencing larger growth losses due to their higher heat stress and drought sensitivity. In these places, trees often react to environmental problems such as drought, which causes a general decrease in growth (Chapter 3). Chapter 2 illustrates that wetter coastal areas have more consistent growth patterns, even if rising VPD and heat stress during hot summers are impacting these locations. These geographical differences stress the need for creating customized forest management plans considering the particular meteorological and environmental conditions of every region.
Rising temperatures, combined with a prolonged drought, present a twofold threat to European beech from heat and drought. Severe physiological stress brought on by high temperatures and water shortages throughout the growing season lowers growth rates and raises death risk. Particularly sensitive to these combined stressors, beech populations in dry regions aggravate the consequences of heat and water shortages (Chapter 3). This emphasizes the need for coordinated management methods addressing heat and drought to promote beech forest long-term survival in the face of increasing temperatures.2025-05-2