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Träfflista för sökning "WFRF:(Carlsson E.) ;mspu:(doctoralthesis)"

Sökning: WFRF:(Carlsson E.) > Doktorsavhandling

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1.
  • Granberg, Åsa, 1977- (författare)
  • Microbotryum violaceum on Silene dioica : understanding traits that influence plant-pathogen interactions
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The dynamics of a plant-pathogen interaction vary both within and among species. Both spatial structuring and specific genetic and life-history characteristics will affect the interaction and the outcome of a potential co-evolution between the two organisms. In this thesis I have studied the interaction between the wild perennial herb Silene dioica and its automictic, obligate anther smut Microbotryum violaceum MvSd. From the plant perspective, I have examined different aspects of biochemical resistance in S. dioica to M. violaceum MvSd. From the pathogen perspective, I have focused on the breeding system of M. violaceum MvSd and its connection to fitness and distribution of genetic diversity. I have used varying methods; glasshouse trails involving inoculation of plants with the pathogen, classical Mendelian analysis involving controlled crosses between plants, microscopic studies of spores and molecular DNA-analysis. With the results I demonstrate that resistance to M. violaceum MvSd in S. dioica can be specific to the attacking pathogen strain and also spatially highly diverse both within and among populations within a metapopulation. Together, these factors are likely to delay the establishment of the disease within host populations and reduce the spread and amount of disease, once it has been established. The results also suggest that the specific resistance expressed against two different M. violaceum MvSd strains were determined by separate gene systems and that, in both cases, the resistance was simply inherited. This implies a potential for relatively rapid response to M. violaceum-induced selection in S. dioica populations variable for resistance. My results also show that automixis clearly is the predominating breeding system of M. violaceum MvSd, similarly to what earlier has been shown for M. violaceum MvSl. Furthermore, I found lower levels of neutral genetic diversity in M. violaceum MvSd in the northern parts of Sweden, compared to what has been found in populations in more southern Europe. This result is consistent with predictions that populations in the outer regions of a species distribution have lower levels of genetic variation. Moreover, populations were highly differentiated in northern Sweden, which could have been generated by high selfing rates, genetic drift and high population turnover rates, all factors that coincide with life-history and ecology of M. violaceum MvSd. However, despite the general low variability in neutral genetic markers, I did find variation in fitness related traits, both within and among populations, as well as differences in infection ability between strains, suggesting there is a potential for co-evolution between S. dioica and M. violaceum MvSd in the area. To summarize, this thesis reflect a plant-pathogen system that is highly influenced by constant colonisation-extinction dynamics, which is likely to have influenced both the genetics of resistance in the plant and the breeding system of the pathogen and thus also the interaction between the two organisms.
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2.
  • Jaiteh, Mariama (författare)
  • New Paradigms in GPCR Drug Discovery : Structure Prediction and Design of Ligands with Tailored Properties
  • 2020
  • Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
    • G protein-coupled receptors (GPCRs) constitute a large superfamily of membrane proteins with key roles in cellular signaling. Upon activation by a ligand, GPCRs transduce signals from the extracellular to the intracellular environment. GPCRs are important drug targets and are associated with diseases such as central nervous system (CNS) disorders, cardiovascular diseases, cancer, and diabetes. Currently, 34% of FDA-approved drugs mediate their effects via modulation of GPCRs. Research during the past decades has resulted in a deeper understanding of GPCR structure and function. Moreover, recent breakthroughs in structural biology allowed the determination of several atomic resolution GPCR structures. New paradigms in GPCR pharmacology have also emerged that can lead to improved drugs. Together, these advances provide new avenues for structure-based drug discovery. The work in this thesis focused on how the large amount of structural data gathered over the last decades can be used to model GPCR targets for which no experimental structures are available, and the use of structure-based virtual screening (SBVS) campaigns to identify ligands with tailored pharmacological properties. In paper I, we investigated how template selection affects the virtual screening performance of homology models of the D2 dopamine receptor (D2R) and serotonin 5-HT2A receptor (5-HT2AR). In papers II and III, SBVS methods were used to identify dual inhibitors of the A2A adenosine receptor (A2AAR) and an enzyme, which could be relevant for treatment of Parkinson’s Disease, and functionally selective D2R ligands from a focused library. Finally, we also investigated how structural information can complement computational and biophysical methods to model and characterize the A2AAR-D2R heterodimer (paper IV).
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3.
  • Marklund, Susanna, 1960- (författare)
  • Temporomandibular disorders : incidence, course, and risk factors
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Temporomandibular disorders (TMD) embrace pain and dysfunction in the temporomandibular joint (TMJ) and jaw muscles. TMD is a prevalent condition in the population and constitutes a significant health problem. Knowledge of factors influencing the onset and course of TMD is important in preventive care and development of treatment strategies as well as in clinical decision making. The aim of this thesis was to gain knowledge of whether variations in dental occlusion, bruxism, spinal pain and gender predicted the development and course of TMD. The study population comprised 371 undergraduate dental students. A questionnaire was used to obtain case histories. Clinical examination included the function of the TMJ, jaw muscles, maximal jaw mobility, the morphological occlusion, and contact patterns in centric and eccentric positions. The examinations were performed at start, and after 12 and 24 months. In total, 280 subjects were examined at all three occasions. The incidence of TMJ pain and dysfunction was high among both males and females. The course composed onset, recovery and maintenance resulting in a fluctuating pattern. Females were more likely to have persistent TMJ pain and dysfunction than males. The incidence and persistence of jaw muscle signs and symptoms was high and significantly more common in females. A similar fluctuating pattern as for TMJ pain and dysfunction was found. Crossbite predicted onset and persistence of TMJ pain and dysfunction; mandibular instability in centric positions predicted persistent TMJ pain and dysfunction, as well as persistent jaw muscle signs or symptoms. Reported bruxism increased the risk for TMJ pain and dysfunction but did not significantly affect the course of jaw muscle signs and symptoms. Spinal pain at baseline predicted the onset of jaw pain, headaches, and TMD pain. Signs of TMD at baseline predicted the onset of non-pain symptoms of TMD, jaw pain, headaches, and spinal pain. In conclusion, the results in this thesis show high incidence rates for TMD, headaches, and spinal pain among dental students. Crossbite, mandibular instability, reported bruxism, as well as female gender were identified as contributing risk factors. Spinal pain and TMD mutually predicted each other, indicating common pathophysiological mechanisms and individual vulnerability. The findings support a multidisciplinary approach, and it is recommended that the status and function of the jaw system be considered in patients with spinal pain.
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