Coming dissertations at Uppsala university
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Exploring the role of tryptophan metabolites in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) : Development and application of high resolution mass spectrometry methods
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-536606
Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a severe systemic disorder characterized by neurological, gastrointestinal, inflammatory symptoms and fatigue. Disregulation in tryptophan (TRP) metabolism and excessive kynurenine pathway activation may cause these symptoms. Thus, this thesis investigates TRP in ME/CFS. TRP, a key amino acid, regulates nervous system, immune system, endocrine system, and energy metabolism. The main pathway of TRP metabolism is kynurenine, with a minor percentage shuttled towards serotonin biosynthesis, a brain-essential neurotransmitter. Kynurenine metabolism generates kynurenic acid (neuroprotective) and quinolinic acid (neurotoxic).
Our current knowledge of TRP metabolism in ME/CFS is insufficient. Few studies have quantified TRP in ME/CFS, and even fewer have employed high-resolution mass spectrometry, essential for accurate measurements and comprehensive metabolomics. Additionally, many studies disregarded factors like age and sex, which influence TRP metabolite levels. Lastly, preclinical research on the neuroprotective effects of KYN as a potential treatment is notably lacking
To address these research questions, we developed an accurate and comprehensive analytical method using liquid chromatography coupled with high-resolution mass spectrometry. This method quantifies TRP and its metabolites, along with the vitamins B2 and B6, essential for the enzymes in this pathway. Additionally, we measured the oxidative marker hypoxanthine and the amino acids tyrosine and phenylalanine, which compete with TRP to cross the blood-brain barrier, and limit its availability in the brain. We then employed the, TRP method and untargeted metabolomics, to compare the metabolic profiles of ME/CFS patients with those of healthy individuals, considering age and sex. Moreover, the effects of the menstrual cycle on TRP levels were examined by correlating 11 steroids with TRP metabolites. Additionally, the tissue distribution of kynurenine was investigated following both acute and chronic administration in a preclinical model.
The untargeted study found alterations in the vitamin B3, arginine-proline, aspartate-asparagine, L-Adrenaline and S-Adenosyl-L-homocysteine pathways . While, the targeted approach revealed decreased levels of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in ME/CFS patients. In addition, hypoxanthine and phenylalanine was elevated in ME/CFS patients, suggesting hypoxia and altered amino acid metabolism. The study found strong relationships between TRP metabolites and steroids during the menstrual cycle, suggesting hormones affect this pathway. Preclinical findings showed that kynurenine administration resulted in region-specific effects, with a potential neuroprotective effect in the hippocampus. These studies open avenues for further exploration of TRP metabolism, particularly in relation to ME/CFS and the impact of steroid hormones on this metabolic pathway.
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When you happen to know a good spot : A study on recreational anglers' relationships to angling settings in Sweden
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-535173
Careful, responsible use of nature is required to halt the continuing degradation of ecosystems while fostering the invaluable relationships between humans and nature. Recreational angling (i.e. recreational fishing with rod and reel) can be a way for people to shape meaningful connections to nature, to other people, and to oneself, but if performed irresponsibly, the activity can pose a threat to already vulnerable ecosystems. In the search for responsible recreational fisheries, researchers have identified angler stewardship as a promising way forward that could safeguard the meaningful relationships between anglers and nature, while minimizing ecological impacts. One of the potential pathways from angling participation to angler stewardship that researchers have identified is sense of place, or the relationships between anglers and angling settings. In this thesis, I present an empirical examination of this pathway.
I used psychometric measurement scales, administered through quantitative, online angler surveys at two recreational fisheries in Sweden, to test the associations between various dimensions of angler diversity, anglers’ sense of place, and their intentions to support the angling setting through acts of loyalty and stewardship. I present my findings through four research papers. Paper I revealed the implications of angler diversity to anglers’ perceptions of fish stock trends at a river-fishing destination. Paper II showed how angling experience and residency status influenced the meanings and attachments anglers held for an island destination. Paper III and IV confirmed structural relationships between the anglers’ interpretations of the angling setting, their attachment to the setting, and their willingness to support the angling setting through acts of loyalty (III) and stewardship (IV).
Based on my findings, I conclude that the responding anglers were attitudinally and behaviorally diverse, and that this diversity spilled over into their relationships to the angling setting. The angling activity, and their relationships to this activity, acted as a lens that shaped their interpretations of the angling setting and their sense of connectedness to this setting. The thesis shows that angling settings are meaningful places to which anglers can form lasting bonds that may motivate place-based supportive intentions. However, I found that these intentions depended on the anglers’ interpretations of the angling setting, which are subjected to (environmental) change. Overall, the thesis expands our knowledge of the role of sense of place as a potential pathway towards promoting angler stewardship and shaping responsible recreational fisheries.
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Diagnosing Demand Flexibility : On the limitations of price signals
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-533319
Mitigating the risks of catastrophic climate change requires wide-scale electrification and the rapid decarbonization of the energy sector. This transformation poses serious challenges to the management of electricity grids, ranging from increasingly intermittent generation to capacity constraints. One of the primary approaches employed to deal with these problems is demand-side flexibility (DSF), which applies a variety of policies that are broadly intended to manipulate electricity demand in ways that are conducive to the needs of the grid. Central to this approach are price signals, which convey information to users through electricity prices or incentives intended to elicit certain changes in behavior. The efficacy of price signals in fostering DSF has been limited and ambiguous. This thesis explores limitations in the current DSF strategy and its reliance on price signals, aiming to provide an understanding of its deficiencies and lay a foundation for alternative strategies.
The findings have been organized into two tracks. The first concerns the internalization of price signals, shedding light on how only a minority of residential users are qualified to make informed decisions in responding to price signals. The results suggest that the strict attribution of a low response to “weak” price signals or to cognitive difficulties is misplaced, and that the failure of DSF policies may partly stem from a general ambivalence towards electricity consumption. The second track concerns the design of price signals and illustrates inconsistencies between their alleged goals and the behaviors that they would hypothetically elicit. These inconsistencies partially stem from the architecture of the electricity market but are also the outcome of a trade-off between the complexity of electricity pricing and the desire to render price signals comprehensible.
Both of these tracks revolve around “functional” limitations, focusing on how price signals operate as instruments of behavioral change. The thesis also outlines a set of “structural” limitations that instead concern the fundamental reliance on price signals as the main mechanism for fostering DSF – a phenomenon described as the “price signal paradigm”. Under a paradigm that prioritizes free markets, minimal government involvement and a perception of users as price-responsive utility maximizers, policymakers have shifted the burden of responsibility onto users while constraining themselves to the limited role of information providers and signal designers. The implications of these findings are that policymakers should explore alternatives that shift responsibility back to system-level actors that are better suited for coordinating and fostering DSF.