| 1. |
- Johansson, Karin, 1970-
(author)
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Interaction Between Drosophila melanogaster mbn-2 Cells and Bacteria
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Innate immunity relies on a repertoire of germline-encoded non-rearranging pattern recognition receptors that bind to invariant microbial surface molecules. This event initiates a number of signal transduction cascades that lead to humoral and cellular defense responses like synthesis of antimicrobial peptides, phagocytosis and coagulation – mechanisms that efficiently fight infectious microorganisms and have been evolutionary conserved to exist in parallel with the antibody-based adaptive immunity found in vertebrates. The fruit fly, Drosophila melanogaster represents a widely used animal model for studies of a pristine innate immune system. Its immune responsive intracellular signalling pathways display a high degree of similarity with the NF-κB /Rel-signalling pathways that mediate the inflammatory response in mammals. Insects are also vectors for medically important parasitic diseases which can trigger immune responses in the vector so basal knowledge about the regulation and function of insect immune systems can contribute to our understanding of inflammation and microbial disease in higher animals and open new strategies for biological vector control. Drosophila hemocytes play a key role in executing and coordinating local and systemic defenses in response to infection. This thesis describes in vitro studies of Drosophila gene expression in response to bacterial infection using the larval hemocyte-like cell line – mbn-2. Our results show that immune challenge with bacterial cell wall components and intact live bacteria induces differential gene expression that gives clues to how cellular immune responses could be activated and regulated.
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| 2. |
- Junkunlo, Kingkamon
(author)
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Regulation of hematopoiesis in the freshwater crayfish, Pacifastacus leniusculus : role of transglutaminase
- 2017
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Doctoral thesis (other academic/artistic)abstract
- The freshwater crayfish, Pacifastacus leniusculus, has been used as a model for studying hematopoiesis or blood cell production or hematopoiesis and immunity. The work of this thesis aims to investigate the impact of factors such as ROS signaling, Ast1, and the PVF/PVR signaling pathway in controlling stem cell behavior during hematopoiesis and specifically the role of the crosslinking enzyme transglutaminase (TGase) in regulation of hematopoiesis.The role of ROS in crayfish hematopoiesis was characterized by using the antioxidant named NAC to inhibit ROS production. Low ROS level resulted in a prolonged decrease in hemocyte numbers and a combined injection of LPS and NAC caused a slower rate of new hemocyte production. A low ROS level in cell cultures supplemented with crude Ast1 was found to inhibit cell spreading and a high extracellular TGase activity was detected on the surfaces of APC and HPT cells. We suggest that ROS serves as a prime signal to control proliferation and differentiation of progenitor cells by affecting extracellular TGase activity. We reported an inhibitory effect of Ast1 on TGase enzyme activity and on its crosslinking activity and consequently Ast1 affects the clot formation and thus coagulation by inhibiting the crosslinking activity of the TGase enzyme. Secretion of the clot protein (CP) and the production of CP filament network between spreading cells were observed in HPT cell cultures in vitro. In the presence of CP together with Ast1 in 3D-collagen-I cultures, HPT cells were found to be more elongated and they formed chains of cells throughout the surrounding matrix. In the HPT tissue, CP was located around the HPT cells or around the lobules of HPT, and thus, CP was demonstrated to be a part of ECM and to possibly function together with collagen in generating a suitable environment for HPT progenitor cells. The inhibition of PVF/PVR downstream signaling pathway by Sunitinib malate resulted in a dramatic change of cell morphology and induction of an increase cell surface area during cell culture. The addition of crude Ast1 into the cell cultures in vitro enhanced this effect. Consequently, cell migration was stimulated and a high extracellular TGase activity on HPT cell surface was found after this inhibition. In conclusion, the work in this thesis provides new insight in understanding the role of the extracellular matrix (ECM) and extracellular TGase activity in controlling stem cell activity.
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| 3. |
- Lundberg, Christina, 1972-
(author)
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Screening for Atherosclerosis with Magnetic Resonance Imaging and Ultrasound
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Atherosclerosis is a major cause of death and disability worldwide. Although traditional risk factors can identify the healthy or severely affected individuals, sudden lethal outcome is still frequent in those suggested as intermediate in risk for cardiovascular events (CVE). Adding imaging to the traditional scoring systems might improve risk stratification.This thesis investigates whether the addition of magnetic resonance imaging (MRI) and ultrasound (US) to traditional risk factors might render atherosclerosis suitable for mass screening, selective screening or screening in research settings.In paper I the carotid arteries were assessed in six different manners (carotid intima media thickness (CIMT) in two different locations, presence of plaque, number of plaques, plaque size and plaque composition) using US. More than 800 Caucasian subjects were assessed at ages 70 and 75, and outcome examined at 80 years of age. Plaques with an area exceeding 10mm2 in the bulb were found to be most closely related to CVE.Paper II established that carotid plaque volume measured with MRI did not correlate with carotid plaque area assessed with US. MRI reached the highest levels of reproducibility of the two methods.Paper III used the previously created total atherosclerotic score (TAS), a scoring system based on whole body magnetic resonance angiography (WBMRA) that assesses global atherosclerosis. TAS was found to predict CVE in 305 PIVUS-subjects at age 70 years during 5 years of follow-up. The risk for CVE was found to be eightfold with TAS>0.In paper IV CIMT was assessed with US at ages 70 and 75 years. CIMT at baseline, but not the change in CIMT over five years, was significantly related to TAS, thus suggesting carotid changes to correlate with atherosclerosis throughout the body.In conclusion, in research settings WBMRA and MRI, as well as US, can be used for screening and following up of atherosclerotic changes, as their predictive values and reproducibility are good. US might be feasible in selective screening but none of these methods are as of now suitable for mass screening.
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| 4. |
- Ornstein, Petra
(author)
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On predictions, measurement, and causal inference : Essays on statistical correlations and statistical applications in labor market economics and criminology
- 2022
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Doctoral thesis (other academic/artistic)abstract
- This thesis consists of five papers covering a broad range of statistical themes, from prediction via correlation measures to causal inference.Paper I uses a nationally representative survey of separated Swedish women to examine whether men who strive to control their partners during their relationships are more likely to stalk or assault their ex-partners after separation. The empirical analysis shows that basic measures of control behaviors explain 18% of the variance in stalking victimization and 8% of the assault victimization. The predictive value of the constructed measures of control is shown to by far surpass those of other common risk markers included in the analysis.Paper II presents asymptotic properties of Spearman’s rank correlation for variables with finite support. For variables with finite support, the population version of Spearman’s rank correlation has been derived. Using this result, convergence to a normal distribution irrespectively of dependence is shown, and the asymptotic variance is derived. A small simulation study indicates that the asymptotic properties are of practical importance.Paper III proposes a robust version of the polychoric correlation, a parametric measure of the correlation between two unobserved continuous variables when the observed variables are discrete. Robust polychoric correlation is shown to be consistent and asymptotically normal. Results from a systematic Monte Carlo simulation suggest that the new estimator has better robustness properties than normality based maximum likelihood estimation of the polychoric correlation, to negligible efficiency costs.Paper IV reports results from a large-scale randomized experiment evaluating whether a supported employment rehabilitation intervention strategy can improve labor market opportunities for young adults on disability pension better than regular vocational rehabilitation. In total, 1,062 individuals were randomly assigned between interventions. The main result shows that 18 months after the start of the project, participants offered supported employment have work rates that are approximately 10 percentage points higher than participants who received regular rehabilitation.Paper V estimates consequences of interpersonal violence on victims. Using rich administrative population data for Sweden, individuals who visited a hospital in the years 1998 to 2002 due to assault are compared to individuals who did not have a hospital visit due to assault at that time, but who were statistically indistinguishable from the individuals of interest in the four years prior to the incident. The results suggest that violent crime has large and persistent effects on mortality, suicide, earnings, work status, disposable income, as well as on the number of days on sick leave. Specifically, an assault leading to a hospital visit is estimated to convey losses amounting to 1.4 million SEK per victimized woman and 1.5 million SEK per victimized man, whereof more than 80 percent result from excess mortality. Estimates on socio-economic outcomes show robustness against selection on unobserved characteristics. Estimates on mortality and suicides are very robust.
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