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Coming dissertations at Uppsala university

  • Surgical treatment of spinal metastasis Author: Christian Carrwik Link: Publication date: 2021-12-21 08:37

    The aim of this thesis was to study surgical treatment of spinal metastasis from several points of view, with a focus on predictive tools and survival after surgery. 

    Study I includes 315 patients treated surgically at Uppsala University Hospital 2006-2012 due to spinal metastatic disease. Based on the data known at the time of surgery, predictive scores were calculated using four different scoring systems (Tokuhashi, revised Tokuhashi, Tomita and modified Bauer scores). The predictions were then compared with true survival data. All of the scores had a statistically significant correlation to survival but all of them tended to underestimate rather than overestimate survival. 

    Study II focused on patients with an unknown primary tumour (UPT). We reviewed 393 cases treated at Uppsala University Hospital, where 122 (31%) had an unknown primary tumour at the time of surgery. A survival analysis showed that the patients with an UPT had a longer estimated survival compared to the group with a known primary tumour (KPT). The estimated median survival time in the UPT group was 15.6 months, compared to 7.4 months in the KPT group. The mean estimated survival time was 48.1 months in the UPT group and 21.6 months in the KPT group. The difference was statistically significant (p=0.001).

    Study III is a retrospective multi-registry study linking the Swedish spine surgery database Swespine with the Swedish Cause of Death (CoD) Register. The analysis included 1820 patients who underwent surgery due to spinal metastatic disease at 19 hospitals in Sweden 2006-2016. The study showed that both the mean and the median estimated survival time after surgery are well above the recommended three months threshold for surgery, suggesting that surgical treatment could be indicated in even more cases. 

    In study IV, prognostic tools were revisited with a validation study of PathFx 3.0, an online open-source tool to estimate survival for patients with skeletal metastases. A cohort of 668 patients treated at Uppsala University Hospital and Karolinska University Hospital were included in the study and the results indicate that PathFx 3.0 could predict survival after treatment with good reliability, especially for patients with long expected survival. As PathFx can be updated to reflect advancements in oncological treatment, this type of tool is probably more useful than the rigid point-based scoring systems evaluated in study I. 

  • Fungal molecular ecology in boreal forests and challenges associated with unidentified environmental DNA sequences Author: Kerri Kluting Link: Publication date: 2021-12-20 14:33

    Many fungi are characteristically difficult to observe and collect, making the process of documenting the world’s fungal diversity challenging. The vast majority of fungal species are undescribed. The use of DNA sequencing technologies has revolutionized the study of fungal diversity by facilitating the detection of new species, the investigation of community  structure and dynamics, and the elucidation of evolutionary relationships. In this dissertation, I focus on filling in some of the many gaps in our understanding of fungal diversity and community ecology in boreal pine forests through the use of DNA sequence data. In the first half of this thesis, a metabarcoding approach is used to study the composition of fungal communities found in the soil of a Lithuanian coastal pine forest and in association with the bark beetle Tomicus piniperda in Swedish pine forests. In the second half, two different approaches are taken to describe taxa detected in environmental DNA. In paper I, I demonstrate how soil microhabitats, defined based on mineral vs organic soil type and root presence or absence, vary with respect to a suite of abiotic factors and shape fungal community composition belowground. These microhabitats support functionally and taxonomically distinct fungal communities and support the overall fungal diversity of the site through niche variation. In paper II, the relationships between a) the fungal communities found on and in bark beetles from forests that have been affected by forest fire and forests that have not, b) pine phloem that has been colonized by bark beetles and phloem that has not at two different post-colonization time points, and c) phloem chemical nutrients are described. In paper III, the diversity of species within the fungal class Archaeorhizomycetes in the soil of a Swedish pine forest was studied, and two new species are described using an integrative taxonomic approach that relies on environmental DNA sequence data as taxonomical evidence. Finally, in paper IV, a new class is described to accommodate a lineage previously detected in environmental DNA, and its first known species is described based on isolates collected during the study of paper III, one of which serves as the type specimen.

  • Functional analyses of growth and development in the liverwort Marchantia polymorpha Author: Anja Billhardt Link: Publication date: 2021-12-20 12:33

    Land plants developed from a freshwater charophycean algae about 500 million years ago. Today, they consist of two main clades, the vascular plants and the non-vascular bryophytes including hornworts, liverworts and mosses. To adapt to challenges within a terrestrial habitat, the first land plants evolved a diversity of hormonal and genetic pathways regulating growth and development. Analyses regarding these networks are mainly based on the angiosperm Arabidopsis thaliana. Genes of other land plant lineages that are inexistent in Arabidopsis are often not considered in functional studies, resulting in an incomplete picture of land plant evolution. The remarkable phylogenetic position of bryophytes makes them interesting for studies of gene function as they might carry different characteristics compared to e.g. angiosperms. In difference to vascular plants, the liverwort Marchantia polymorpha harbors a small, low genetic redundant genome containing most gene families present in Arabidopsis. Thus making it an advantageous model organism to determining specific gene function. 

    This thesis focuses on describing how dormancy and the circadian clock regulate growth in Marchantia. To avoid growth during unfavorable environmental, plants apply dormancy programs. Marchantia applies dormancy in gemmae, small asexual propagules produced by the shoot in a cup. Gemmae are dormant in the cup until they are dispersed by rain and subsequently germinating. I show that high levels of absisic acid (ABA), inhibits gemmae germination within the cup. Gemmae with a manipulated MpCYP707A, a gene involved in catabolism of ABA and seed dormancy regulation in Arabidopsis, showed altering dormancy suggesting that ABA homeostasis is fundamental for regulation of gemmae dormancy. Because dormant gemmae are not physically attached to the cup it has been speculated that the signal maintaining dormancy of gemmae is a gas. I found that gemmae mutated in positive and negative regulators of the ethylene signaling pathway showed decreased and increased dormancy respectively, suggesting that ethylene regulates dormancy through ABA.

    I also found that the circadian clock in Marchantia regulates growth of the thallus, possibly by affecting auxin levels. The circadian clock in land plants appears in structural differences between species. I showed that the gene MpDET1 has a conserved structure but harbors a different function compared to Arabidopsis. In Arabidopsis, growth is regulated by the clock through PIF genes, but in Marchantia, this pathway appears independent of PIF. Although the clock mechanism appear well conserved in land plants, its structure and function has evolved, creating diversity between land plant groups.