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A mucus hydrogel covers the intestinal epithelium, protecting the host from passing food and resident gut microbiota. The mucus consists of a highly organized glycoprotein network, mainly produced by goblet cells. In the distal colon, where microbial abundance is highest, goblet cells continuously secrete mucus, which “grows” by expansion, forming a gradient from an inner nearly sterile layer to an outer loose layer where bacteria reside. This pushes microbes away from the host epithelium, thereby reducing the risk of infection and inflammation.

The gut microbiota is predominantly composed of bacteria and is strongly influenced by diet. Individuals in industrialized societies exhibit reduced microbial diversity compared to those in non-industrialized societies – a difference partly attributed to the Western-style diet (WSD), which is low in dietary fiber and high in simple sugars and saturated fat. In mice fed a WSD, microbiota diversity is reduced, and the mucus barrier is weakened, as seen by a slower mucus growth rate and increased bacterial penetration, which raises the risk for harmful microbial interactions. Similar microbial and mucus alterations are observed in patients with inflammatory bowel disease (IBD). While mucus properties are microbiota-dependent, the underlying regulatory mechanisms are still largely elusive. This thesis aims to clarify these mechanisms by studying the colonic mucus barrier in a WSD environment, with both human and mouse microbiota. Moreover, the effects of structures previously untested for their mucus-influencing properties during WSD feeding are evaluated in mice.

In study 1, the impact of diet-induced changes in the human microbiota on the colonic mucus barrier was studied by transplanting fecal samples into microbiota-depleted mice. Healthy participants increased their fiber intake over three months, and their microbiota was collected before and after the intervention. When transplanted into mice, only the high-fiber-derived microbiota maintained mucus growth under WSD feeding and reduced the pathogen load during intestinal infection. The bacterial taxon Blautia was enriched in the high-fiber group, and Blautia coccoides emerged as a key regulator of mucus integrity through the production of the short-chain fatty acids (SCFAs) acetate and propionate. These metabolites were shown to stimulate mucus growth via the free-fatty acid receptor 2 (Ffar2), revealing a previously unrecognized mechanism by which microbial metabolites directly impact mucus integrity.

In studies 2 and 3, the mucus-influencing effects of bovine milk-derived casein glycomacropeptide (CGMP) and human milk oligosaccharide (HMO) structures were examined in WSD-fed mice. CGMP is a glycosylated protein found in cheese whey, while HMOs are breast milk components with over 200 known structures. Both GCMP and HMOs share structural similarities with mucin glycans and may act as decoy substrates for bacterial degradation under low-fiber conditions. In study 2, CGMP structures improved mucus growth rate, where specifically, a highly sialylated CGMP (HSA) increased propionate levels and the relative abundance of Bifidobacteria, a bacterium previously linked to mucus maintenance. In study 3, specific HMO structures enhanced mucus integrity and improved mucus penetrability in a mouse model for IBD. HMO-dependent mucus modulation could be linked to changes in bacterial composition, increased SCFA levels and glycan-targeting enzyme activities. These findings emphasize the structure-specific effects of CGMPs and HMOs and their distinct modulation of microbiota–mucus interactions.

In summary, this thesis reveals new insights into how microbial metabolites regulate the mucus barrier in the Western gut and highlights novel strategies to be exploited for treating mucus-associated disorders such as IBD.

Control Flow Integrity (CFI) is a well-established mitigation against control-flow hijacking attacks arising from memory corruption vulnerabilities. Over the past two decades, numerous CFI mechanisms have been proposed and integrated into modern compilers and software ecosystems. Despite this progress, CFI remains difficult to adopt in practice, and deployment decisions, compatibility constraints, and engineering overhead strongly influence its real-world security impact. 

This dissertation investigates Control Flow Integrity from the perspective of practical adoption and deployability. Rather than treating CFI as a purely theoretical protection, it examines how CFI is selected, integrated, and maintained in real-world software systems, and why these steps often fall short of idealized designs. The dissertation is structured around four complementary studies that together trace the path from measurement to guidance, to deployment experience, and finally to automated enforcement. 

The first study presents a large-scale empirical analysis of deployed binaries to assess the current state of LLVM-CFI adoption across major software platforms. It shows that while CFI deployment is increasing in some ecosystems, it remains uneven and limited, leaving substantial portions of the attack surface unprotected. The second study addresses the lack of practical guidance for developers by introducing a systematic taxonomy that maps LLVM-CFI variants to common classes of memory corruption vulnerabilities. This taxonomy provides actionable recommendations to support incremental, informed adoption of CFI in existing codebases.

The third study examines the practical challenges of deploying CFI in a complex, production-grade runtime. Through a detailed case study of integrating LLVM-CFI into a modern Java Virtual Machine, it demonstrates that compatibility issues, manual exclusions, and maintenance effort are central obstacles to effective enforcement, even when strong CFI mechanisms are available. These findings highlight the gap between CFI as designed and CFI as deployed. 

Building on these insights, the dissertation introduces an automated framework for CFI policy generation and enforcement. By reducing manual effort and mitigating compatibility barriers, this approach enables more consistent and scalable CFI deployment across large and evolving software systems.

Overall, the dissertation shows that the effectiveness of Control Flow Integrity in practice is shaped less by the availability of CFI mechanisms than by the feasibility of adopting them. By combining empirical measurement, practical guidance, deployment experience, and automation, this work contributes toward a more realistic and actionable understanding of CFI and provides concrete support for improving its deployment in real-world software systems.

Extracellular ATP (eATP) is increasingly recognized as a key regulator of stress, damage and protective responses across biological systems. While its signalling role in mammalian cells is well established, the mechanisms governing its function and regulation in the context of host-microbe interactions remain incompletely understood. This thesis explores how eATP levels are sensed and modulated by bacteria, and how its dysregulation impacts host physiology during infection. We first demonstrate that E. coli and related Gammaproteobacteria possess enzymatic pathways capable of degrading eATP to hypoxanthine, thereby actively modulating eATP concentrations in the intestinal environment. Through genome-wide screening and biochemical validation, we identified key bacterial factors involved in this degradation process and confirmed their functional relevance in vitro, in enterocyte infection models, and in vivo. These findings reveal a previously underappreciated microbial strategy to modify intestinal inflammation by controlling eATP availability.

Further, we show that E. coli does not merely degrade eATP but also responds to it as an environmental signal. Gene expression and metabolomic analyses revealed that eATP exposure reshapes bacterial physiology, regulating genes involved in metabolism, stress responses, antimicrobial resistance and virulence. This dual role of eATP as both a substrate and a signal highlights its importance in shaping microbial behavior and host- microbe interactions.

Extending the scope beyond bacterial systems, we investigated systemic eATP dynamics in the context of viral infection in a longitudinal study of 394 COVID-19 patients. Plasma eATP levels were elevated during acute SARS-CoV-2 infection and remained dysregulated for up to a year, independently of disease severity. High eATP correlated with markers of coagulation, kidney function and chronic immune activation. Notably, eATP peaks were associated with the development of humoral immunity during acute infection, and were further elevated following COVID-19 vaccination, suggesting a role for eATP in shaping long-term immune trajectories.

Together, this thesis presents a unified view of eATP as a central mediator connecting microbial processes, host immune signalling, and systemic inflammation. By integrating bacterial and viral contexts, it advances our understanding of how eATP contributes to health and disease, and opens new avenues for therapeutic strategies targeting ATP- dependent signalling.

There is an increased emphasis on the diverse meanings and values of forests as well as the heterogeneous private forest ownership, both of which have proved challenging in policy, planning, and management of forests. This thesis contributes social science insights to the field of forest research related to social and emotional dimensions of forests and forest ownership. Concepts from the academic field of human geography are used to provide understandings of the varied ways in which private forest owners and rural residents may form and interpret their relationships, meanings, feelings, values and practices related to forests and forest properties. A qualitative research approach was conducted in Sweden through the use of face-to-face interviews with 51 private forest owners and focus-group interviews with residents of the Dalasjö village in Vilhelmina municipality.      

The thesis is based on four individual papers. Paper 1 shows how geographical distance and non-residency do not automatically explain variations in forest owners’ feelings of closeness to or distance from their forest properties. Drawing on the concept of ‘sense of place’, the results suggest that non-resident owners may have close emotional ties to their forest properties as a result of their particular social and ownership contexts, such as family links or being second-home owners. In Paper 2, an analysis of ‘gendering’ in private forest ownership – understood as the ongoing social practices of ‘doing’ gender differences in the interaction with space, place and bodies – establishes both dichotomised and varied perceptions and experiences of gender differences and practices in forest ownership. It underlines that gender differences were sometimes ‘done’ as a means of ‘othering’ women, but also as a means of negotiating or resisting the gendered forest ownership and the production-oriented context of forestry in Sweden. Paper 3 demonstrates the importance of private forest owners’ feelings connected to their ownership and the place of their property in their relationship to public use and public planning interests. A conceptual framework of private forest ownership was developed in this paper consisting of ‘property rights’, ‘ownership feelings’ and ‘sense of place’. The paper highlights the need to take into account social and emotional dimensions of forest ownership when addressing public interests in relation to private land. With the case of Dalasjö, Paper 4 explores how ‘forest social values’ may be understood and applied in a rural setting. The findings reveal diverse and context-specific, place-based forest social values, as well as challenges in how to translate and apply forest social values in a planning process. 

This dissertation explores the construction of womanhood and female subjectivities in the educational discourse of the late Ottoman Empire and early Republican Turkey between 1859 and 1933. It approaches women’s education through multiple entry points, including girls’ rüşdiyye (secondary) schools, women’s education’s relation to “the West,” stereotypes of women, and representations of muallimes (female teachers). The analysis draws on a comprehensive range of sources, including secondary school curricula, women’s magazines, education journals, literary works, and autobiographical texts. Methodologically, the thesis employs historical case study evaluation, qualitative thematic analysis, and the analytical concepts of stereotypes and countertypes. The overarching theoretical framework of gender and educationalisation is supported by the concepts of patriarchal bargaining, Occidentalism, and social disciplining. The dissertation argues that education functioned as a central site through which womanhood was negotiated, modernised, regulated, and politicised. Four interrelated sub-studies demonstrate that 1) women were prioritised in state-led moral regulation and social disciplining through education; 2) female subjectivities were shaped by ambivalent engagements with “the West,” where Occidentalist tensions functioned as patriarchal bargains; 3) women developed flexible stereotypes through educational discourse to navigate social transformation in the making of the “ideal patriotic Turkish woman;” and 4) the muallime emerged as both a product and an active agent of modernisation, negotiating tensions between professionalism, nationalism, domesticity, and morality. Overall, women were positioned as key targets of state and societal regulation, with educational discourse framing motherhood, morality, health, and patriotism as core female responsibilities. At the same time, women actively appropriated educationalisation to legitimise access to schooling, articulate professional identities, and claim social and economic agency. These strategies enabled participation in public life while simultaneously reaffirming gendered, classed, and national hierarchies by recasting structural inequalities as problems for education to solve. The dissertation contributes to the history of women’s education in Turkey by offering a gender-aware reading of early girls’ curricula and by foregrounding women’s own educational discourse. It demonstrates that similar curricular reforms imposed stronger moral expectations on girls than on boys and reveals clear divergences between male- and female-authored representations of womanhood. By combining gender, educationalisation, and Occidentalism, the study provides a theoretical framework for analysing women’s agency in a non-Western context, showing that educational discourse functioned as a site of negotiation rather than a linear path toward emancipation.

Modern technologies like machine learning and data-driven decision systems, depend on solving large and often highly complex optimization problems. These problems rarely come with simple shapes or smooth surfaces; instead, they can twist and bend in ways that make finding good solutions surprisingly difficult. This thesis explores two ideas that help us navigate such complexity more effectively. 

The first idea focuses on acceleration and investigates how optimization algorithms can reach good solutions faster while using only basic information such as function values and gradients. By studying these algorithms through a continuous-time analysis, we show that many of the fastest methods behave like carefully designed dynamical systems. This perspective not only clarifies why acceleration happens, but also allows us to design fast algorithms and understand how they behave in the presence of noisy information. 

The second idea focuses on a mathematical structural assumption called difference-of- convex (DC) programming, which captures a remarkably wide range of nonconvex problems. By leveraging this structure, we develop practical algorithms that avoid costly operations like projections or high dimensional gradient evaluations, making them efficient for large-scale applications. Through the connection between DC programming and the classical Expectation–Maximization (EM) algorithm, we develop more scalable EM variants and provide the first general performance guarantees for them. 

This dissertation examines F. Scott Fitzgerald’s short stories as they were first published in magazines, sharing page space with illustrations and advertisements. The presence and interplay of media types and paratexts in the magazine stories may significantly impact the reading experience, creating different interpretative possibilities. In this study, an intermedial framework is used to examine select magazine stories. This framework, which also takes inspiration from periodical and multimodal studies, considers the illustrations, advertisements, and short stories as media types with specific characteristics.

The intermedial analyses focus on three stories published at different stages of the most active period in Fitzgerald’s writing career. The earliest story, “Winter Dreams” (1922) was published in the two magazines MacLean’s and Metropolitan, “Diamond Dick and the First Law of Woman” (1924) appeared in Hearst’s International, and “Family in the Wind” (1932) was published in the Saturday Evening Post. Each case study foregrounds a central theme—nostalgia, gender, and nature, respectively—chosen for its prominence in Fitzgerald’s work, its cultural significance during the Jazz Age, and its continued relevance today. Across all three chapters, the dissertation examines media combination, showing how interactions between literary text and illustration consistently nuance or alter thematic emphases found in the text alone. Transmediation, or how the narrative of one media type is transformed by another, becomes particularly important in discussions about the illustrators’ selection and visual development of narrative scenes, and media representation informs analyses of how references to other media types such as film and news function within the stories.

The case study in Chapter 1 focuses on how the illustrations and advertisements in the two magazines interact with nostalgic aspects of the literary text of “Winter Dreams,” the illustrations and the ads magnifying youth and youthful romantic experiences. The case study in Chapter 2 examines how Fitzgerald takes inspiration from the dime novel to bring to the fore various character types that interrogate gender identity, but how the illustrations in the magazine, in contrast, present a rather conservative construction of gender. The case study in Chapter 3 highlights how Fitzgerald is stylistically influenced by the media types of film and news in “Family in the Wind.” The sense of urgency and veracity around the tornado that impacts the town in the story, contrasts to how the magazine layout emphasizes illustrations that focus on human drama.

The dissertation contributes to Fitzgerald studies by foregrounding original publication contexts, to literary studies through close readings of lesser-studied works, to intermedial studies via the extensive application of an intermedial framework on the magazine stories, and to periodical studies by demonstrating the value of integrating intermedial and periodical methodologies.

Background: Today, more than 95% of children with congenital heart disease (CHD) reach adulthood, allowing many to consider parenthood. While research has focused on pregnancy-related morbidity and mortality, universal situations of childbirth and parenthood for this group remain sparsely explored. Given the lifelong follow-up and increased health risks for adults with CHD, the condition may influence parental experiences. The aim of this thesis was therefore to improve understanding of the universal aspects of childbirth and parenthood in adult CHD, by integrating reported outcomes with the perspectives of affected adults and midwives.

Methods: This thesis includes four studies.  In the register studies (study I and II), data were obtained from two national quality registers. to compare women with CHD with matched controls in terms of self-rated health before, during and after pregnancy (study I), and breastfeeding two days and four weeks after birth (study II). In the other, semi-structured interviews were used to explore experiences of parenthood among adults with CHD, and how midwives articulate their role in the childbirth of women with CHD.

Results: During and after childbirth: No significant difference in the prevalence of good self-rated health after childbirth was observed between women with CHD and their matched controls (CHD 81% vs. controls 82%, p = 0.46). However, breastfeeding rates four weeks after birth differed between the two groups (CHD 84% vs. controls 89%, p = 0.006), although the difference was relatively small. Sociodemographic factors demonstrated strong associations with both poor self-rated health and lower breastfeeding rates among women with CHD. Parenthood with adult CHD: Parenthood led to the vulnerability due to CHD becoming more apparent. The presence of a co-parent and social network was emphasised as supportive in daily life. Also important was the opportunity to process life experiences and emotions with professionals. Midwives’ role when women with CHD give birth: Midwives described an interprofessional communication gap. They experienced stress due to the great responsibility they felt, in combination with a lack of background knowledge about CHD. This resulted in an ideological dilemma, as the time they would have used to provide normal childbirth support was instead devoted to medical tasks. 

Conclusions: Parenthood with CHD is highly individual and shaped not only by the condition itself but also by sociodemographic factors and personal health perception. Nevertheless, the need for emotional support must be acknowledged, as becoming a parent may heighten one’s sense of vulnerability. Furthermore, communication between the professionals involved in childbirth among women with CHD needs to be improved to strengthen the understanding of responsibilities and knowledge.

This thesis investigates ultrafast charge carrier dynamics in disordered nanostructures using femtosecond optical pump probe spectroscopy. The main aim is to understand how photoexcited electronic distributions evolve on femtosecond to picosecond timescales and how nanoscale morphology reshapes the transient optical response and the associated relaxation pathways. Broadband pump probe measurements are combined with optical modelling to relate time dependent changes in transmission to transient modifications of the complex permittivity, electronic damping, and energy transfer to the lattice. 

Ultrafast dynamics are studied in two plasmonic metal systems. For nanoporous gold, the transient transmission response is strongly enhanced and broadened compared with a continuous film. The broadband negative signal extends below the equilibrium interband onset, consistent with higher transient electron temperatures in the porous network that increase Fermi smearing and enable additional 5d to 6sp excitation pathways at lower photon energies. The relaxation is slower than in bulk gold, and modelling with an extended two temperature description combined with an effective medium optical treatment captures both the broadened spectra and the modified recovery, linking the response to morphology-controlled energy deposition and electron to lattice energy flow. 

For disordered copper nano island films, the transient transmission is strongly dispersive in the visible range, with negative and positive contributions that evolve in time due to the interplay of pump induced absorption and bleaching. In both Au and Cu, the measurements show that disorder and nanoscale connectivity reshape the spectral line shape and modify the apparent relaxation dynamics by changing the effective optical response and the effective metal volume involved in energy deposition. 

A complementary case study on polycrystalline NiO thin films extends the investigation to a transition metal oxide under sub band gap excitation, The transient reflectivity shows a prompt negative response followed by recovery that is well described by a biexponential model with a fast component on the order of a few tens of femtoseconds and a slower sub picosecond component. In addition, the thesis documents the generation and characterization of few-cycle structured light pulses carrying orbital angular momentum with controlled polarization states, providing an experimental platform for future ultrafast studies with tailored excitation fields 

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition involving the upper and lower motor neurons, leading to progressive muscle atrophy, paresis, and death, usually by paralysis of the respiratory muscles. The majority of patients are considered sporadic with no reported hereditary background. However, about 5-10% of patients have a genetic predisposition. Mutations in the gene encoding superoxide dismutase 1 (SOD1) are one of the most common causes of familial ALS. Over 240 mutations spread over the entire SOD1 gene have been described in ALS. SOD1 plays a significant role in the cellular defense machinery against damage caused by the superoxide anion radical. A large body of evidence advocates for a gain of novel toxic function to be the major cause of SOD1-linked ALS by forming pathological aggregates. However, children homozygous for mutations resulting in total loss of SOD1 function develop a motor neuron disease phenotype within the first 6 months of life. This indicates a potential threshold below which the loss of SOD1 activity is deleterious. The approval of the antisense oligonucleotide tofersen designed to reduce SOD1 mRNA levels and hence prevent protein aggregation, marked the beginning of a new era where a subgroup of patients has access to disease-modifying therapy with a real clinical effect. Not all patients respond to treatment, and most continue to clinically progress, albeit at a slower pace, and the reason for this is not fully understood.

This thesis aims to investigate the role of SOD1 enzymatic activity in ALS. We used specific SOD antibodies and immunocapture, combined with biochemical and quantitative methods, to investigate and better understand the effects of altered SOD1 levels and activity in CSF and answer questions emerging from these findings.

We quantified SOD1 content in different tissues, including blood, thereby mapping SOD1 abundance in the CNS and peripheral tissues as a baseline for SOD1-reducing therapies. Even though SOD1 is an abundant protein, it accounts for only 0.16% of total protein levels, which is 10-fold lower than stated in the literature.

ALS mainly affects the CNS, and CSF reflects the status of the CNS better than erythrocytes. We therefore developed a method that allows the specific measurement of SOD1 activity in CSF. We then analyzed SOD1 activity in 171 CSF samples collected from ALS patients with and without SOD1 mutations and compared them with controls. The SOD1 activity varies greatly in CSF. Consequently, we asked how SOD1 activity is influenced by SOD1-reducing drugs and studied SOD1 activity in longitudinal CSF samples of ALS patients treated with tofersen up to 3 years. The activity was reduced to different degrees in all patients. The treatment response time varied from 4 to 12 months and is clinically relevant for deciding whether the drug has a beneficial effect or not in individual ALS patients, and might allow for individual dosing.

In CSF samples, a band on immunoblots 3 kDa below monomeric SOD1, indicated a N-truncated variant of SOD1 in CSF. Further investigation revealed the truncation site to be between amino acids 26 and 27 and that the cleaved peptide stays connected to the truncated SOD1 monomer in a folded state. With mass spectrometry, the cleaved peptide was identified to be identical to the N-terminal sequence found in native SOD1. The truncation event does not seem to have an effect on SOD1 misfolding. We could not explain what causes the truncation of SOD1 in CSF, and our data indicate that N-truncation does not contribute to ALS pathogenesis.

Citizenship education requires well-trained teachers to support young people’s participation in democratic life where digital technologies and social practices are inseparable. Social science teacher educators prepare student teachers for this work amid complex institutional dynamics and rapidly shifting demands for digital citizenship and professional digital competence including artificial intelligence. This thesis aims to contribute knowledge on how these teacher educators approach teaching to teach for digital citizenship in such postdigital contexts, exploring and analyzing the conditions for such teaching within institutional arrangements.

Employing a postdigital lens within an emergent research design, the thesis comprises four interconnected studies. These encompass theoretical analysis of digital citizenship conceptualizations, document reviews and interviews with teacher educators in Core Education Subjects and social science subject courses at a third of Sweden’s teacher education institutions, and a national survey across all institutions. Analytical approaches included qualitative content analysis, reflexive thematic analysis, and convergent mixed methods with quantitative priority.

The results show systematic variation in teacher educators’ approaches to digital citizenship education. Like in literature, conceptualizations vary from instrumental approaches to recognizing entangled sociotechnical relations. Despite general acknowledgment of digital citizenship’s importance, the substantial variation in conceptualizations extends to roles, responsibilities, and professional digital competence. Disciplinary background and schoolteacher experience emerge as key factors shaping both competence and approaches, alongside various institutional arrangements that amplify variation. The compounded result is fragmentation, where digital citizenship risks becoming an institutional blind spot with implications for student teacher preparation equivalence.

Practical implications include institutional support through program coordination, enabling cross-disciplinary collaboration, professional development, and policy clarity. These include a reframing of professional digital competence from person-centered toward ecologically situated capabilities responsive to institutional and sociotechnical contexts.

Vibrio cholerae releases outer membrane vesicles (OMVs) that package virulence factors, yet how vesicular deliveryreshapes host responses, particularly in cancer cells, remains incompletely defined. This thesis characterises the role of OMVs-associated virulence factors in regulating cellular signalling in epithelial cells. Furthermore, the thesis aims toaddress the antitumour activities of the V. cholerae zinc metalloprotease haemagglutinin protease A (HapA), with emphasison how OMV association modulates potency and mechanism. Using intestinal epithelial monolayers, 3D spheroids, and intestinal organoids, we demonstrate that V. cholerae OMVs canassociated with the epithelial cell membrane and are rapidly internalized through various endocytic mechanisms into theintracellular compartments. The OMV-associated HapA causes disruption of tight- and adherens-junction proteins inpolarized Caco-2 cells, and intestinal organoids. Moreover, the OMV-associated HapA compromises barrier integrity moreefficiently than the purified enzyme. OMV-associated HapA is internalised by epithelial cells via endocytosis. The HapA then selectively degraded tight- and adherens-junction proteins, including claudin, ZO-1, and β-catenin, resulting in loss ofepithelial cohesion. Importantly, compare to the soluble protein, OMV-associated HapA was biologically more active indisruption of epithelial cells.To assess effects on carcinoma cells, we analysed V. cholerae secretome mutants and identified HapA as the principal factorreducing epithelial cancer cell viability. Mechanistically, HapA cleaves protease-activated receptors PAR1 and PAR2 atnoncanonical sites distinct from human proteases, eliciting an early, transient MEK–ERK activation that culminates incaspase-7–dependent apoptosis. We further uncover a PAR-independent mechanism in colorectal carcinoma cells whereby HapA directly uses β-catenin as asubstrate, attenuating Wnt/β-catenin signalling, downregulating Axin2 and Cyclin D1, suppressing tumor cell proliferation,and enforcing G0/G1 arrest. Collectively, these studies define dual antitumour mechanisms for HapA: PAR1/2 reprogramming of MEK–ERK dynamicsand direct attenuation of β-catenin signalling. The findings also establish OMVs as a potent vehicle that enhance proteaseefficacy at epithelial and tumour interfaces. This work highlights therapeutically relevant host–pathogen interactions andsupports the exploration of OMV-based delivery or protease-targeted strategies in cancer therapy.

What makes a tree a tree?

The capacity to form and maintain woody tissue has been key for the ecological success and economic relevance of forest trees. While fundamental cell types and developmental processes are common to most trees, there are significant differences between the two main tree lineages: angiosperms and gymnosperms.

Comparative genomic research has dramatically expanded our understanding of plant genome evolution, with several studies demonstrating that the transcriptional programmes underlying xylogenesis are largely conserved between lineages. Modern research suggests that both speciation and intraspecific variation are often the result, not only of coding sequence mutations, but also of shifts in gene expression regulation.

The aim of this thesis was to elucidate how genomic architecture and regulatory programmes govern wood development and secondary growth evolution. By combining comparative genomics with high-resolution spatial transcriptomics across angiosperm and gymnosperm species, this research establishes a multi-layered regulomic and evolutionary framework for studying wood formation.

The results identified multiple regulatory gene groups linked to wood evolution and development and generated significant genomic resources. In particular, chromosome-scale reference genomes were generated for two conifer species and an "evo-devo" resource for wood was established using a high-resolution comparative regulomic framework across wood differentiation layers in six tree species. Furthermore, a modified DNA Affinity Purification sequencing (DAP-seq) protocol was developed and optimised for mature woody tissues.

These resources can facilitate the identification of conserved and lineage-specific regulators, providing a critical blueprint for precision breeding and targeted genome engineering. Ultimately, these findings can contribute to the development of advanced materials and the transition toward a carbon-neutral bioeconomy.