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Aging is associated with bone loss, which can lead to osteoporosis and high fracture risk. This coincides with the enhanced formation of bone marrow adipose tissue (BMAT), suggesting a negative effect of bone marrow adipocytes on skeletal health. Increased BMAT formation is also observed in pathologies such as obesity, type 2 diabetes and osteoporosis. However, a subset of bone marrow adipocytes forming the constitutive BMAT (cBMAT), arise early in life in the distal skeleton, contain high levels of unsaturated fatty acids and are thought to provide a physiological function. Regulated BMAT (rBMAT) forms during aging and obesity in proximal regions of the bone and contain a large proportion of saturated fatty acids. Paradoxically, BMAT accumulation is also enhanced during caloric restriction (CR), a life-span extending dietary intervention. This indicates, that different types of BMAT can form in response to opposing nutritional stimuli with potentially different functions.
To this end, two types of nutritional interventions, CR and high fat diet (HFD), that are both described to induce BMAT accumulation were carried out. CR markedly increased BMAT formation in the proximal tibia and led to a higher proportion of unsaturated fatty acids, making it similar to the physiological cBMAT. Additionally, proximal and diaphyseal tibia regions displayed higher adiponectin expression. In aged mice, CR was associated with an improved trabecular bone structure. Taken together, these findings demonstrate, that the type of BMAT that forms during CR might provide beneficial effects for local bone stem/progenitor cells and metabolic health. The HFD intervention performed in this thesis showed no effect on BMAT accumulation and bone microstructure. RNA Seq analysis revealed alterations in the composition of the collagen-containing extracellular matrix (ECM).
In order to investigate the effects of glucose homeostasis on osteogenesis, differentiation capacity of immortalized multipotent mesenchymal stromal cells (MSCs) and osteochondrogenic progenitor cells (OPCs) was analyzed. Insulin improved differentiation in both cell types, however, combination of with a high glucose concentration led to an impaired mineralization of the ECM. In the MSCs, this was accompanied by the formation of adipocytes, indicating negative effects of the adipocytes formed during hyperglycemic conditions on mineralization processes. However, the altered mineralization pattern and structure of the ECM was also observed in OPCs, which did not form any adipocytes, suggesting further negative effects of a hyperglycemic environment on osteogenic differentiation.
In summary, the work provided in this thesis demonstrated that differentiation commitment of bone-resident stem cells can be altered through nutrient availability, specifically glucose. Surprisingly, both high nutrient supply, e.g. the hyperglycemic cell culture conditions, and low nutrient supply, e.g. CR, can induce adipogenic differentiation. However, while CR-induced adipocyte formation was associated with improved trabecular bone structure, adipocyte formation in a hyperglycemic cell-culture environment hampered mineralization. This thesis provides further evidence for the existence of different types of BMAT with specific functions.
Nils-Hendrik Grohmann beschäftigt sich mit dem noch andauernden Stärkungsprozess der UN-Menschenrechtsvertragsorgane. Er analysiert, welche rechtlichen Befugnisse die Ausschüsse haben, ob sie von sich aus Vorschläge einbringen können und inwieweit sie ihre Verfahrensweisen bisher aufeinander abgestimmt haben. Ein weiterer Schwerpunkt liegt auf der Zusammenarbeit zwischen den verschiedenen Ausschüssen und der Frage, welche Rolle das Treffen der Vorsitzenden bei der Stärkung spielen kann.
Cross-sectional associations of dietary biomarker patterns with health and nutritional status
(2024)
Development of a CRISPR/Cas gene editing technique for the coccolithophore Chrysotila carterae
(2024)
Electricity production contributes to a significant share of greenhouse gas emissions in Europe and is thus an important driver of climate change. To fulfil the Paris Agreement, the European Union (EU) needs a rapid transition to a fully decarbonised power production system. Presumably, such a system will be largely based on renewables. So far, many EU countries have supported a shift towards renewables such as solar and wind power using support schemes, but the economic and political context is changing. Renewables are now cheaper than ever before and have become cost-competitive with conventional technologies. Therefore, European policymakers are striving to better integrate renewables into a competitive market and to increase the cost-effectiveness of the expansion of renewables. The first step was to replace previous fixed-price schemes with competitive auctions. In a second step, these auctions have become more technology-open. Finally, some governments may phase out any support for renewables and fully expose them to the competitive power market.
However, such policy changes may be at odds with the need to rapidly expand renewables and meet national targets due to market characteristics and investors’ risk perception. Without support, price risks are higher, and it may be difficult to meet an investor’s income expectations. Furthermore, policy changes across different countries could have unexpected effects if power markets are interconnected and investors able to shift their investments. Finally, in multi-technology auctions, technologies may dominate, which can be a risk for long-term power system reliability. Therefore, in my thesis, I explore the effects of phasing out support policies for renewables, of coordinating these phase-outs across countries, and of using multi-technology designs. I expand the public policy literature about investment behaviour and policy design as well as policy change and coordination, and I further develop an agent-based model.
The main questions of my thesis are what the cost and deployment effects of gradually exposing renewables to market forces would be and how coordination between countries affects investors’ decisions and market prices.. In my three contributions to the academic literature, I use different methods and come to the following results. In the first contribution, I use a conjoint analysis and market simulation to evaluate the effects of phasing out support or reintroducing feed-in tariffs from the perspective of investors. I find that a phase-out leads to investment shifts, either to other still-supported technologies or to other countries that continue to offer support. I conclude that the coordination of policy changes avoids such shifts.. In the second contribution, I integrate the empirically-derived preferences from the first contribution in to an agent-based power system model of two countries to simulate the effects of ending auctions for renewables. I find that this slows the energy transition, and that cross-border effects are relevant. Consequently, continued support is necessary to meet the national renewables targets. In the third contribution, I analyse the outcome of past multi-technology auctions using descriptive statistics, regression analysis as well as case study comparisons. I find that the outcomes are skewed towards single technologies. This cannot be explained by individual design elements of the auctions, but rather results from context-specific and country-specific characteristics. Based on this, I discuss potential implications for long-term power system reliability.
The main conclusions of my thesis are that a complete phase-out of renewables support would slow down the energy transition and thus jeopardize climate targets, and that multi-technology auctions may pose a risk for some countries, especially those that cannot regulate an unbalanced power plant portfolio in the long term. If policymakers decide to continue supporting renewables, they may consider adopting technology-specific auctions to better steer their portfolio. In contrast, if policymakers still want to phase out support, they should coordinate these policy changes with other countries. Otherwise, overall transition costs can be higher, because investment decisions shift to still-supported but more expensive technologies.
Light is the essential energy source for plants to drive photosynthesis. In nature, light availability is highly variable and often fluctuates on very short time scales. As a result, plants developed mechanisms to cope with these fluctuations. Understanding how to improve light use efficiency in natural fluctuating light (FL) conditions is a major target for agronomy.
In the first project, we identified an Arabidopsis thaliana plant that showed reduced levels of rapidly inducible non-photochemical quenching (NPQ). This plant was devoid of any T-DNA insertion. Using a mapping-by-sequencing approach, we successfully located the causal genomic region near the end of chromosome 4. Through variant investigations in that region, we identified a deletion of about 20 kb encompassing 9 genes. By complementation analysis, we confirmed that one of the deleted genes, VTC2, is the causal gene responsible for the low NPQ. Loss of VTC2 decreased NPQ particularly in old leaves, with young leaves being only slightly affected. Additionally, ascorbate levels were almost abolished in old leaves, likely causing the NPQ decrease by reducing the activity of the xanthophyll cycle. Although ascorbate levels in younger leaves were reduced compared to wild-type plants, they remained at a comparably higher level. This difference may be due to the VTC2 paralog VTC5, which is expressed at a higher level in young leaves than in old ones.
Plants require the PROTON GRADIENT REGULATION 5 (PGR5) protein for survival in FL. pgr5 mutants die because they fail to increase the luminal proton concentration in response to high light (HL) phases. A rapid elevation in ∆pH is needed to slow down electron transport through the Cytochrome b6 f complex (photosynthetic control). In FL, such lack of control in the pgr5 mutants results in photosystem I (PSI) overreduction, reactive oxygen species (ROS) production, and cell death. Decreases in photosystem II (PSII) activity introduced by crossing pgr5 with PSII deficient mutants
rescued the lethality of pgr5 in FL. PGR5 was suggested to act as part of the ferredoxin-plastoquinone reductase (FQR), involved in cyclic electron transfer around PSI. However, the proposed molecular role of PGR5 remains highly debated. To learn more about PGR5 function, we performed a forward genetic screen in Arabidopsis thaliana to identify EMS-induced suppressor mutants surviving longer when grown in FL compared to pgr5 mutants (referred to as ”suppressor of pgr5 lethality in fluctuating light”, splf ). 11 different candidate genes were identified in a total of 22 splf plants.
Mutants of seven of these genes in the pgr5 background showed low Fv/Fm values when grown in non-fluctuating low light (LL). Five of these 4genes were previously reported to have a role in PSII biogenesis or function. Two others, RPH1 and a DEAD/DEAH box helicase (AT3G02060), have not been linked to PSII function before. Three of splf candidate genes link to primary metabolism, fructose-2,6-bisphosphatase (F2KP ), udp-glucose pyrophosphorylase 1 (UGP1 ) and ferredoxin-dependent glutamate synthase (Fd-GOGAT ). They are characterized by the fact that they survive longer in FL than pgr5 mutants but do not procede beyond the early vegetative
phase and then die.
Plant metabolism serves as the primary mechanism for converting assimilated carbon into essential compounds crucial for plant growth and ultimately, crop yield. This renders it a focal point of research with significant implications. Despite notable strides in comprehending the genetic principles underpinning metabolism and yield, there remains a dearth of knowledge regarding the genetic factors responsible for trait variation under varying environmental conditions. Given the burgeoning global population and the advancing challenges posed by climate change, unraveling the intricacies of metabolic and yield responses to water scarcity became increasingly important in safeguarding food security.
Our research group has recently started to work on the genetic resources of legume species. To this end, the study presented here investigates the metabolic diversity across five different legume species at a tissue level, identifying species-specific biosynthesis of alkaloids as well as iso-/flavonoids with diverse functional groups, namely prenylation, phenylacylation as well as methoxylation, to create a resource for follow up studies investigation the metabolic diversity in natural diverse populations of legume species.
Following this, the second study investigates the genetic architecture of drought-induced changes in a global common bean population. Here, a plethora of quantitative trait loci (QTL) associated with various traits are identified by performing genome-wide association studies (GWAS), including for lipid signaling. On this site, overexpression of candidates highlighted the induction of several oxylipins reported to be pivotal in coping with harsh environmental conditions such as water scarcity.
Diverging from the common bean and GWAS, the following study focuses on identifying drought-related QTL in tomato using a bi-parental breeding population. This descriptive study highlights novel multi-omic QTL, including metabolism, photosynthesis as well as fruit setting, some of which are uniquely assigned under drought. Compared to conventional approaches using the bi-parental IL population, the study presented improves the resolution by assessing further backcrossed ILs, named sub-ILs.
In the final study, a photosynthetic gene, namely a PetM subunit of the cytochrome b6f complex encoding gene, involved in electron flow is characterized in an horticultural important crop. While several advances have been made in model organisms, this study highlights the transition of this fundamental knowledge to horticultural important crops, such as tomato, and investigates its function under differing light conditions. Overall, the presented thesis combines different strategies in unveiling the genetic components in multi-omic traits under drought using conventional breeding populations as well as a diverse global population. To this end, it allows a comparison of either approach and highlights their strengths and weaknesses.
Nowadays, innovative and entrepreneurial activities and their actors are embedded in interdependent systems to drive joint value creation. Innovation ecosystems and entrepreneurial ecosystems have become established system-level concepts in management research to explain how value transpires between different actors and institutions in distinct contexts. Despite the popularity of the concepts, researchers have critiqued their theoretical depth, conceptual distinctiveness, as well as operationalization and measurement (Autio & Thomas, 2022; Klimas & Czakon, 2022). Furthermore, in light of current-day challenges, research has yet to address how context impacts innovation and entrepreneurial ecosystems and their actors and elements (Wurth et al., 2022).
The aim of this cumulative thesis is to provide a deeper understanding of the conceptualization, operationalization, and measurement of innovation and entrepreneurial ecosystems and investigate how contextual factors can influence the overall ecosystem and its key actors. To this end, bibliometric and empirical-qualitative methods, as well as narrative and systematic literature reviews, are employed. After introducing the research scope and key concepts in Chapter 1, a systematic literature review to operationalize and measure the concept of innovation ecosystems is conducted, and an integrative framework of its composition is introduced in Chapter 2. In Chapter 3, the innovation journal network is outlined by means of science mapping to determine current and emerging research areas characterizing innovation studies. In Chapters 4 and 5, the interplay between the temporal context of the Covid-19 pandemic and the spatial context of entrepreneurial ecosystems is assessed by focusing on the role of organizational resilience and affordances. The findings shed new light on the dynamics and boundaries of entrepreneurial ecosystems as they move between the spatial and digital realm. Building on this, an integrative framework of digital entrepreneurial ecosystems is presented in Chapter 6. The concluding Chapter 7 summarizes my thesis’s conceptual, theoretical, and empirical insights, highlighting implications, limitations, and promising future research avenues.
The findings of this cumulative thesis contribute to the theoretical and conceptual advancement of ecosystems in innovation and entrepreneurship by providing insights into the measurement and operationalization of its elements. Furthermore, the results show that contextual factors, such as crisis events or institutional circumstances, influence innovation and entrepreneurial ecosystems and their actors, calling for a more nuanced consideration of ecosystem configurations and dynamics. By drawing from the theory of affordances, the elements that actually afford value to the actors and how they shift between the physical and digital realm are portrayed. Based on these findings, this thesis introduces novel frameworks and conceptual advancements of the configurations and boundaries of innovation and (digital) entrepreneurial ecosystems, laying the foundation for a renewed understanding of how to design, orchestrate, and evaluate ecosystems today and in the future.
This dissertation examines the lack of clarity in the scientific literature regarding gender and negotiation performance. It is often claimed that men negotiate better than women, yet it is simultaneously emphasized that results strongly depend on context. Through the use of qualitative methods such as content analysis and critical mixed-methods review, the research question: "Are women truly inferior negotiators compared to men?" is addressed. The study comprises a descriptive and an interpretive part. The descriptive section illuminates various interpretations of gender-specific negotiation theory among citing authors, with 67% arguing for a general superiority of men. However, given the high variance in gender-specific differences, the focus should instead be on the context-dependency of negotiation performance. Generalized statements can be made within contexts, but not across them. In the interpretive section, several factors contributing to this misinterpretation are highlighted, including discrepancies in the definition of negotiation performance and distortions in research communication.. From a scientific perspective, this study underscores the need for a nuanced sociological analysis and warns against the one-sided acceptance of inaccurate scientific interpretations. From a practical standpoint, it amplifies the voices of women affected by biased research paradigms. Overall, the dissertation clarifies the theory of gender-specific negotiation performance and advocates for the elimination of biases in scientific discourse.
The biosecurity individual
(2024)
Discoveries in biomedicine and biotechnology, especially in diagnostics, have made prevention and (self)surveillance increasingly important in the context of health practices. Frederike Offizier offers a cultural critique of the intersection between health, security and identity, and explores how the focus on risk and security changes our understanding of health and transforms our relationship to our bodies. Analyzing a wide variety of texts, from life writing to fiction, she offers a critical intervention on how this shift in the medical gaze produces new paradigms of difference and new biomedically facilitated identities: biosecurity individuals.
Seasonal forecasts are of great interest in many areas. Knowing the amount of precipitation for the upcoming season in regions of water scarcity would facilitate a better water management. If farmers knew the weather conditions of the upcoming summer at sowing time, they could select those cereal species that are best adapted to these conditions. This would allow farmers to improve the harvest and potentially even reduce the amount of pesticides used. However, the undoubted advantages of seasonal forecasts are often opposed by their high degree of uncertainty. The great challenge of generating seasonal forecasts with lead times of several months mainly originates from the chaotic nature of the earth system. In a chaotic system, even tiny differences in the initial conditions can lead to strong deviations in the system’s state in the long run.
In this dissertation we propose an emergent machine learning approach for seasonal forecasting, called the AnlgModel. The AnlgModel combines the analogue method with myopic feature selection and bootstrapping. To benchmark the abilities of the AnlgModel we apply it to seasonal cyclone activity forecasts in the North Atlantic and Northwest Pacific. The AnlgModel demonstrates competitive hindcast skills with two operational forecasts and even outperforms these for long lead times.
In the second chapter we comprehend the forecasting strategy of the Anlg-Model. We thereby analyse the analogue selection process for the 2017 North Atlantic and the 2018 Northwest Pacific seasonal cyclone activity. The analysis shows that those climate indices which are known to influence the seasonal cyclone activity, such as the Niño 3.4 SST, are correctly represented among the selected analogues. Furthermore the selected analogues reflect large-scale climate patterns that were identified by expert reports as being determinative for these particular seasons.
In the third chapter we analyse the features that are used by the AnlgModel for its predictions. We therefore inspect the feature relevance (FR). The FR patterns learned by the AnlgModel show a high congruence with the predictor regions used by the operational forecasts. However, the AnlgModel also discovered new features, such as the SST anomaly in the Gulf of Guinea during November. This SST pattern exhibits a remarkably high predictive potential for the upcoming Atlantic hurricane activity.
In the final chapter we investigate potential mechanisms, that link two of these regions with high feature relevance to the Atlantic hurricane activity. We mainly focus on ocean surface transport. The ocean surface flow paths are calculated using Lagrangian particle analysis. We demonstrate that the FR patterns in the region of the Canary islands do not correspond with ocean surface transport. It is instead likely that these FR patterns fingerprint a wind transport of latent heat. The second region to be studied is situated in the Gulf of Guinea. Our analysis shows that the FR patterns seen there do fingerprint ocean surface transport. However, our simulations also show that at least one other mechanism is involved in linking the Gulf of Guinea SST anomaly in November to the hurricane activity of the upcoming season.
In this work the AnlgModel does not only demonstrate its outstanding forecast skills but also shows its capabilities as research tool for detecting oceanic and atmospheric mechanisms.
The development of seeds in angiosperms starts with a complex process of double fertilization, involving the fusion of the maternal egg cell and central cell with two paternal sperm cells. This gives rise to the embryo and the nourishing endosperm, which are then enclosed by the seed coat, derived from the maternal integuments. The growth of the seed coat in Arabidopsis thaliana (Arabidopsis) is actively inhibited before fertilization by epigenetic regulators known as Polycomb Group (PcG) proteins. These proteins deposit a repressive histone mark called H3K27me3, which must be removed to enable seed coat formation. In this thesis, I explored the mechanism of removal of H3K27me3 marks from the integument cells following fertilization, which allows for seed coat formation. We hypothesized that this removal should be primarily facilitated by histone demethylases from the JMJ family and potentially influenced by the plant hormones Brassinosteroids (BRs). This hypothesis was supported by the expression patterns of the JMJ protein REF6 and of BR related genes, which are specifically expressed in the integuments and in the seed coat. Moreover, mutations in both these pathways lead to developmental defects, such as reduced ovule viability and delayed seed coat growth. Our research provides evidence suggesting that BR signalling is likely involved in recruiting JMJ-type histone demethylases to target loci responsible for seed coat growth. Moreover, we have discovered an additional pathway through which BRs regulate seed coat development, independent of their influence on H3K27me3 marks. This finding emphasizes the diverse roles of BRs in coordinating seed development, extending beyond their well-known involvement in plant growth and development. Furthermore, I explored the role of another epigenetic mark, DNA methylation, in fertilization-independent (or autonomous) seed formation in Arabidopsis. For this, we utilized epigenetic Recombinant Inbred Lines (epiRILs) and thus identified an epigenetic Quantitative Trait Locus (epiQTL) on chromosome II, potentially responsible for the larger autonomous seed size observed in DNA methylation mutants. Overall, this thesis significantly enhances our comprehension of the intricate relationship between epigenetic modifications, hormonal signaling, and plant reproductive processes. It offers valuable insights into the genetic mechanisms governing both sexual and asexual seed formation, while also presenting potential avenues for the engineer of advantageous traits in agricultural crops.