| 1. |
- Chisalita, Simona I., 1972-
(författare)
-
Expression and function of IGF-I and insulin receptors in human micro- and macrovascular cells
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insulin-like growth factor and insulin are phylogenetically closely related polypeptides and have large structural and biological similarities. Low circulating insulin-like growth factor-I (IGF-I), diabetes as well as insulin resistance have been implicated in the pathogenesis of cardiovascular disease, but the mechanisms involved are still not clear. Furthermore, little is known about direct effects of insulin-like growth factor-I (IGF-I) and insulin on human micro- and macrovascular cells.In these studies we investigated the expression and function of insulin-like growth factor-I receptors (IGF-IR) and insulin receptors (IR) in human micro- and macrovascular endothelial cells and in human coronary artery smooth muscle cells.Our results showed expression of both IGF-IR and IR in human dermal microvascular (HMVEC), aortic (HAEC) umbilical vein (HUVEC) and coronary artery (HCAEC) endothelial cells as well as in human coronary artery smooth muscle cells (HASMC). The gene expression of IGF-IR was several times more abundant than that of IR. Ligand binding studies confirmed that the IGF-IR was severalfold more abundant than the IR. It also demonstrated that insulin and glargine interacted with the IGF-IR with thousand- and hundredfold, respectively, less potency than IGF-I itself. The presence of IGF-IR and IR proteins and activation of their β-subunits was revealed by immunoprecipitation and Western blot analysis in human macrovascular endothelial cells and in coronary artery smooth muscle cells. At physiological concentrations (≤10-9 M) IGF-I and insulin activated their cognate receptors. The presence of hybrid IR/IGF-IR was shown through detection of the β-subunit for IGF-IR and IR on the same membrane by Western blot after immunoprecipitation with specific antibodies against either IGF-IR or IR, implying coprecipitation of the IGF-IR β-subunit and the IR β-subunit. The inability of physiological concentrations of insulin to phosphorylate IR β-subunit immunoprecipitated with IGF-IR antibodies and that IGF-I at physiological concentration activates the IR β-subunit is another evidence for the presence of the hybrid IR/IGF-IR. At physiological concentrations (≤10-9 M) IGF-I stimulated DNA synthesis and glucose incorporation into human coronary artery smooth muscle cells (HCASMC) and DNA synthesis in microvascular endothelial cells (HMVEC), but not in human macrovascular endothelial cells (HCAEC or HUVEC). No effect of insulin was found. Although physiological concentrations of insulin (≤10-9 M) were able to activate IR, insulin had no biological effects on the vascular cells studied. A possible explanation is that the insulin receptor signalling is too attenuated due to the presence of hybrid IR/IGF-IR and low number of IR expressed in the cells studied. Regarding the safety in the use of glargine, we show that glargine has 10-fold higher affinity for IGF-IR than human insulin. However, the glargine concentrations obtained in vivo during diabetes treatment is too low to affect the IGF-IR.In conclusions our studies provide experimental evidence that human micro- and macrovascular endothelial and vascular smooth muscle cells express both IGF-IR and IR. Our in vitro data suggest that the cells studied are sensitive to IGF-I, but insensitive to insulin and this is due to the preponderance of IGF-IR and presence of hybrid IR/IGF-IR.
|
|
| 2. |
- Forsström, David, 1981-
(författare)
-
The use and experience of responsible gambling tools : An explorative analysis of user behavior regarding a responsible gambling tool and the consequences of use
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Responsible gambling tools are an intervention that is designed to decrease gambling among individuals with an at-risk gambling behavior. Studies have indicated that responsible gambling tools can decrease gambling behavior, but little is known about how this intervention is used by gamblers. The aim of the present thesis was to explore different facets of the use, experience and functions of these tools. Study I used descriptive statistics and latent class analysis (LCA) combined with multinomial regression to explore the use of the responsible gambling tool Playscan among 9528 gamblers (regular and at-risk gamblers). The participants had volunteered to use the tool. The functions of the tool had a high rate of initial use but a low rate of repeated use. The LCA identified five user classes. Two of the classes (self-testers and multifunctional users) were defined as high users of the tool and had a higher risk of developing gambling problems according to multinomial regression. The multifunctional users were characterized by an extensive use of all the functions while the other high usage class had an extensive use of the self-test. The three other classes were as follows: those who did not use the tool, those who visited the tool but did not engage in any of the functions, and those who only used the tool’s advice on how to decrease their gambling. Participants’ reasons for use and non-use of the tool were attributed to their degree of need of the tool and its functions. The tool’s most widely used function was the self-test that investigated the level of negative consequences faced by a user due to his or her gambling. Study II was a qualitative study investigating participants’ views, experiences and their reasons for using the tool. The study was conducted by interviewing 20 volunteer users of the tool. These semi-structured interviews were analyzed by thematic analysis. The results showed that the users had a positive attitude towards the tool and understood its purpose. The self-test was the most widely used function in this sample as well. However, the participants’ positive attitude toward the tool did not effectively encourage them to use it; they displayed low use of the tool’s functions. This paradox was explained by lack of feedback and the fact that some participants did not understand that they had registered to use the tool. Providing more feedback and tailoring the feedback to individual users were seen as ways of bridging the paradox. Study II also found that participants used the gambling website (which Playscan was linked to) in an analogue way, preparing their bets before placing them online. This limited the time they spent on the site and inhibited their use of Playscan. Study III was motivated by the extensive use of the self-test among users in Study I and Study II. The aim of Study III was to investigate the psychometric properties of the self-test (known as GamTest) to better understand how it could be used with Playscan in the most efficient way. Two thousand two hundred and thirty four respondents answered the questionnaire, along with instruments measuring depression, anxiety and another instrument measuring problems due to gambling. Factor analysis, parallel analysis, Cronbach’s alpha, and correlations were used to establish the tool’s psychometric properties. The results yielded a three-factor model, excellent reliability, and high correlation with the Problem Gambling Severity Index (PGSI), endorsing the validity of the self-test. The results also indicated that the questionnaire could be effectively shortened. Overall, the studies show that the tool has an initial high use, low repeated use and that the self-test is the most used feature. In addition, the self-test had good psychometric properties.
|
|
| 3. |
- Jansson, Ulrika, 1977-
(författare)
-
Forest edges in boreal landscapes - factors affecting edge influence
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The boreal forest in Fennoscandia has been subjected to major loss and fragmentation of natural forests due to intensive forestry. This has resulted in that forest edges are now abundant and important landscape features. Edges have documented effects on the structure, function and biodiversity in forests. Edge influence on biodiversity is complex and depends on interactions between many local and regional factors. This thesis focuses on sharp forest edges and their potential to influence biodiversity at the landscape-level. I have developed a method for quantification and characterization of sharp forest edges by interpretation of colour infrared (CIR) aerial photographs in combination with line intersect sampling (LIS) and sample plots. The method was used to estimate density of forest edge in 28 landscapes (each 1600 ha) in northern Sweden, differing in management intensity, landscape composition and geographical location. Forest edges were described in detail using edge, canopy and neighbourhood attributes. By combining these attributes it was possible to classify edges with respect to levels of exposure. A field experiment was conducted to examine the effect of edge contrast on growth of the old forest lichen Usnea longissima. The edge quantification method is accurate and efficient for estimating the length of sharp forest edges on an area basis (edge density, m ha-1) and for collecting detailed attributes of edges and their surroundings. In northern Sweden, the forest edge density is high (54 m ha-1) but varies extensively (12-102 m ha-1) between landscapes. Edge density is strongly correlated with the level of human disturbance and increases towards the southern part of the study area, at lower altitudes were management intensity is highest. Edge orientation, contrast and neighbourhood size shows an immense variation between edges and also varies between edge types. Regenerating edges are generally of higher contrast and face larger neighbourhoods than natural edges. Maintained edges had high contrast but small neighbourhoods. A larger proportion of edges in mature forests are highly exposed to microclimatic edge influence than edges in general. The field experiment revealed that growth of U. longissima was highest near edges where the vegetation on the adjacent area was sheltering, but not shading, the lichen. In the present thesis, I have provided a valuable tool for estimating density of forest edges with potential to yield information on important factors determining edge influence at landscape-level. The large variability in edge density, edge and neighbourhood attributes imply large differences in microclimate anf thus in the potential for ede influence. Management and conservation strategies must incorporate these factors to realistically address edge influence on biota at the landscape-level.
|
|
| 4. |
- Mikaelsson, Rickard, 1975-
(författare)
-
Promoting Democracy : Sweden and the democratisation process in Macedonia
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation contributes to an increased understanding of democracy promotion. Empirically, the study focuses on the multi-faced democratisation process in Macedonia; the official Swedish policy for democracy promotion; and actual Swedish attempts to promote democracy in Macedonia in the period 2000–2006. Theoretically, the study advances an analytical framework, which serves to bring clarity to democracy promotion as a concept. It is argued that democracy promotion embodies six structural components, and should be understood as activities adopted and/or supported by foreign actors, as part of a relationship between the democracy promoter and the recipient country, based on a set of motives and shaped through the use of different strategies, methods and channels. Moreover, the issue of impact is investigated. The analytical framework is used to investigate the character of Swedish democracy promotion, and to develop a typology of the roles of democracy promotion in democratisation processes. It is argued that the Swedish policy for democracy promotion is permeated by a Swedish democratic self-image, eclectic theoretical reflection, and flexibility. In addition, it is argued that Sweden is primarily driven by altruistic and ideological motives, and acts to promote legal and societal democracy, and that the allocation of democracy promotion resources is based on theoretical as well as practical considerations. Macedonia’s democratisation process is analysed, and on the basis of the Swedish attempts to promote democracy in Macedonia, the study advances a typology of the roles of democracy promotion in democratisation processes, these being: educator, initiator, and supporter. Together with the analytical framework, this role typology provides new possibilities to study, and understand, democracy promotion.
|
|
