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Extreme precipitation is occurring with greater frequency and intensity as a result of climate change. Such events boost the transport of allochthonous organic matter (allo-OM) to freshwater ecosystems, yet little is known about the impacts on dissolved organic matter (DOM) quality and seston elemental stoichiometry, especially for lakes in warm climates. A mesocosm experiment located in a Turkish freshwater lake was designed to simulate a pulse event leading to increased inputs of allo-OM by examining the individual effects of increasing water colour (HuminFeed®, HF), the direct effects of the extra energetic inputs (alder tree leaf leachate, L), and the interactions of the single treatment effects (combination of both sources, HFL), along with a comparison with unmanipulated controls. Changes in the DOM quality and nutrient stoichiometry of the allo-OM treatment additions was examined over the course of the experiments. Results indicated that there was an increase of high recalcitrant DOM components in the HF treatment, in contrast to an increase in less aromatic microbially derived molecules for the L treatment. Unexpectedly, seston C:P ratios remained below a severe P-limiting threshold for plankton growth and showed the same temporal pattern in all mesocosms. In contrast, seston N:P ratios differed significantly between treatments, with the L treatment reducing P-limiting conditions, whilst the HF treatment increased them. The effects of the combined HFL treatment indicated an additive type of interaction and chlorophyll-a was highest in the HFL treatment. Our results demonstrate that accounting for the optical and stoichiometric properties of experimental allo-OM treatments is crucial to improve the capacity to explain extrapolated conclusions regarding the effects of climate driven flooding on freshwater ecosystems in response to global climate change.

Shallow lake ecosystems face multiple stressors, including microplastic (MP) pollution, allochthonous dissolved organic matter (allo-DOM or tDOM) inputs, and the impact of climate change on water temperature. With the aim of investigating these human-induced and climate-driven impacts, this thesis discusses the indirect effects of microplastics on ciliates within a trophic cascade, the influence of pulsed allo-DOM with varying qualities on planktonic communities, and the combined effects of warming and terrestrial dissolved organic carbon (tDOC) on bacteria and ciliate dynamics. Through the use of mesocosm experiments, following conclusions were reached. For MP, larger particles were found to influence ciliate biomass and diversity by releasing them from crustacean zooplankton grazing. The allo-DOM experiment revealed that the quality of allo-DOM significantly regulated microbial community biomass and composition, with nonlinear responses (biomass increase followed by a decrease) in bacteria and ciliate dynamics. Lastly, the combined warming and tDOC experiment exhibited complex, non-linear responses in bacteria and ciliate communities where the impacts of tDOC dominated warming impacts on the overall response. Findings of this thesis contribute to a more comprehensive understanding of the complex interplay between anthropogenic influences and natural stressors in aquatic environments to which bacteria and ciliates were quite responsive, informing future research directions and management strategies.

Hepatocellular carcinoma (HCC), the most common primary liver malignancy worldwide, is strongly associated with chronic Hepatitis B Virus (HBV) infection, a significant risk factor. The ubiquitin–proteasome system, central to protein degradation, cellular homeostasis, and cell cycle regulation, has been implicated in the pathogenesis of several cancers, including HCC. Despite this, the specific expression patterns of proteasomal subunits during HBV infection and HBV-induced HCC, as well as the association between mRNA expression of proteasomal subunits and proteasomal activity, remain poorly defined. To address this critical knowledge gap, we analyzed mRNA expression profiles of proteasomal subunits in HBV-infected humanized mouse models to uncover HBV-specific molecular alterations. Our findings revealed that the chymotrypsin-like activity (β5) subunit of the proteasome (PSMB5) is consistently overexpressed following HBV infection. Functional studies demonstrated that β5 deficiency decreases MHC I levels on the cell surface and leads to the accumulation of ubiquitinated proteins, establishing a direct link between β5 overexpression and increased proteasomal activity. Concordantly, HBV-infected patient livers—regardless of HCC status—displayed elevated β5 mRNA/protein levels and enhanced chymotrypsin-like activity. Additionally, analysis of Protein Atlas data revealed that elevated β5 mRNA expression correlates with poor clinical prognosis in HCC patients. In summary, this study highlights how HBV infection induces significant alterations in proteasome function by elevating β5 expression and activity in human and mouse livers. These findings underscore the critical role of proteasomal dysregulation in HBV-associated liver pathology and provide new insights into its involvement in HCC development. Understanding the interplay between HBV infection and proteasome dynamics offers a valuable avenue for the identification of novel therapeutic targets and biomarkers in HCC.