Gastrulation is a fundamental process that reorganizes the primary germ layers to shape the internal and external features of an early embryo. Morphogenetic movements underlying this process can be classified into a variety of different types of cellular movements. I will focus on investigating in this thesis two types of cell movements in the dorsal mesoderm; mediolateral cell intercalation and convergence and extension. During gastrulation, mesoderm cells send protrusions to gain traction on neighboring cells and the surrounding extracellular matrix; a process called mediolateral cell intercalation. Mesoderm cells use this type of cell movement to converge and extend the dorsal mesoderm tissue during gastrulation; a process called convergence and extension. These morphogenetic movements are essential to form the early embryo and are important for later development. There are a number of different proteins involved in regulating the morphogenetic movements during gastrulation. The Planar Cell Polarity Signaling Pathway helps establish individual cell polarity and is activated in dorsal mesoderm cells undergoing convergence and extension. In addition, dorsal mesoderm cells migrate by using integrin receptors and the surrounding extracellular matrix to correctly position the mesoderm in the embryo. I will focus my efforts on analyzing the function of ADAM proteins during Xenopus laevis gastrulation. The ADAM family of metalloproteases is important for a variety of biological processes. ADAM proteins function as ectodomain sheddases by cleaving membrane bound proteins involved in signal transduction, cell-cell adhesion, and cell-extracellular matrix adhesion. I will focus on investigating the roles of two ADAM family members; ADAM13 and ADAM19 during gastrulation. Both ADAM13 and ADAM19 are expressed in the dorsal mesoderm during gastrulation. Throughout early embryonic development, ADAM13 is expressed in the somitic mesoderm and cranial neural crest cells. ADAM19 is expressed in dorsal, neural and mesodermal derived structures such as the neural tube, notochord, the somitic mesoderm, and cranial neural crest cells. Since ADAM13 and ADAM19 are expressed in similar tissues, I investigated if both proteins functionally interacted. I show that a loss of ADAM13 protein in the embryo reduces the level of ADAM19 protein by 50%. In the opposite experiment, a loss of ADAM19 protein in the embryo reduces the level of ADAM13 protein by 50%. This suggests that both ADAM13 and ADAM19 are required to maintain proper protein levels in the embryo. This might be explained through their physical interaction in a cell. The ADAM19 Proform binds to the ADAM13 Proform in cultured cells. Through domain analysis, I show that ADAM19 binds specifically to the cysteine-rich domain of ADAM13. When co-overexpressed in a cell, the level of Mature ADAM13 (compared to the Proform) is reduced suggesting a complex form of regulation. I propose a few hypothetical models that discuss how ADAM19 may function as a chaperone to stabilize and regulate the further processing of ADAM13 protein. Some of the unpublished work discussed in this thesis focuses on the roles of ADAM13 and ADAM19 in the dorsal mesoderm during gastrulation. Specific emphasis is made on investigating the axial mesoderm during notochord formation. I show that ADAM19 affects gene expression important for the A-P polarity of the notochord while ADAM13 does not. The changes in gene expression can be partially rescued by the EGF ligand Neuregulin1β, a known substrate for ADAM19 in the mouse. ADAM13 and ADAM19 are important for convergence and extension movements of the axial mesoderm during gastrulation. Specifically, a loss of ADAM13 or ADAM19 causes a delay in mediolateral cell intercalation resulting in a significantly wider notochord compared to control embryos. These defects occur without affecting dishevelled intracellular localization or the activation of the PCP signaling pathway. However, a loss of ADAM13 or ADAM19 reduces dorsal mesoderm cell spreading on a fibronectin substrate through α5β1 integrin. To conclude, the work presented in this thesis focuses on the similarities and differences of ADAM13 and ADAM19 in the early embryo. Although ADAM13 and ADAM19 are required for normal morphogenetic movements during gastrulation, my data suggests they have different functions. ADAM13 appears to function in regulating cell movements while ADAM19 appears to function in regulating cell signaling. I propose a few hypothetical models that discuss how each ADAM metalloprotease may function in the dorsal mesoderm and contribute to convergence and extension movements during gastrulation.>

Abstrakt Inledning: I Sverige erbjuds alla kvinnor mellan 40-74 år möjlighet till att genomgå en hälsokontroll (screening) av sina bröst. Syftet med mammografiscreening är att hitta patologi så tidigt som möjligt för att kunna tillgodose en gynnsam behandling och för att förhindra dödlig utgång. Röntgensjuksköterskan har en viktig roll i den bilddiagnostiska utredningen. En av röntgensjuksköterskans uppgifter är att framställa röntgenbilder med optimal bildkvalitet samtidigt som patientsäkerheten måste beaktas. Syfte: Syftet var att beskriva faktorer som kan påverka den optimala bildkvaliteten vid mammografiundersökningar. Metod: För att få svar på syftet genomfördes en allmän litteraturöversikt. Vetenskapliga artiklar letades i databaserna PubMed och Cinahl. 15 artiklar sammanställdes och analyserades sedn i tre kategorier. Resultat: Analysen av artiklarna visade på att det finns flera faktorer som kan inverka på den optimala bildkvaliteten vid mammografiundersökningar. Analysen presenterade tre kategorier såsom patientrelaterade aspekter, tekniska parametrar och röntgensjuksköterskans betydelse. Slutsats: Röntgensjuksköterskans kunskaper och kännedom om vilka faktorer som kan inverka på bildkvaliteten är viktig för att minimera brister i bildkvaliteten. För att kvalitetsförbättra mammografiundersökningarna samt bibehålla kunskap krävs kontinuerlig träning och utbildning.

Obstetric interventions and pelvic floor disorders - Abstract One of the principal objectives of obstetric interventions in the second stage of labor is prevention of pelvic floor trauma and associated pelvic floor disorders. The most commonly used and also most frequently discussed interventions are manual perineal protection and episiotomy. The majority of pelvic floor disorders are of subjective nature. Therefore, tools for objectification and severity quantification of these disorders are the key to reliable comparison and identification of the most effective interventions. The aim of the dissertation was to find the most effective modification of manual perineal protection, to compare two frequently used types of episiotomy regarding all pelvic floor disorders and finally to find a consensus on the most suitable instrument for anal incontinence severity assessment. Our studies concerning manual perineal protection experimentally described the direction and extent of perineal deformation during vaginal delivery. The subsequent studies on biomechanical model demonstrated that the most effective method of manual perineal protection in peak perineal strain reduction is when the fingers are placed on the perineum 6 cm laterally and 2 cm ventrally from the posterior commissure at both sides and are...

Obstetric interventions and pelvic floor disorders - Abstract One of the principal objectives of obstetric interventions in the second stage of labor is prevention of pelvic floor trauma and associated pelvic floor disorders. The most commonly used and also most frequently discussed interventions are manual perineal protection and episiotomy. The majority of pelvic floor disorders are of subjective nature. Therefore, tools for objectification and severity quantification of these disorders are the key to reliable comparison and identification of the most effective interventions. The aim of the dissertation was to find the most effective modification of manual perineal protection, to compare two frequently used types of episiotomy regarding all pelvic floor disorders and finally to find a consensus on the most suitable instrument for anal incontinence severity assessment. Our studies concerning manual perineal protection experimentally described the direction and extent of perineal deformation during vaginal delivery. The subsequent studies on biomechanical model demonstrated that the most effective method of manual perineal protection in peak perineal strain reduction is when the fingers are placed on the perineum 6 cm laterally and 2 cm ventrally from the posterior commissure at both sides and are...