Coming dissertations at Uppsala university
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Filosofiämnets didaktik : En studie om det svenska gymnasieämnet filosofi och dess didaktik
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540462
This thesis aims to study the subject-didactic concepts and problems of the philosophy subject in the Swedish upper secondary school.
The study's research design is based on four of John Goodlad's (1979) domains of curricula. These have guided four of the dissertation’s sub-studies.
The first study, which deals with the domain of ideological curricula, analyzes debates between Swedish philosophers during the years 1978–1986 regarding the purpose and content of the subject. The second study, which deals with the domain of formal curricula, analyzes the historical syllabuses that guide philosophy in Swedish upper secondary school from the year 1935 until today.
The third study, which deals with the domain of perceived curricula, is an interview study with experienced philosophy teachers. The fourth study, which deals with the domain of experienced curricula, is a survey study where students in philosophy have answered questions before and after their philosophy studies.
The data collections have been analyzed through grounded theory, resulting in clusters of themes emerging from the statements of teachers and students.
The key findings are analyzed as six subject-didactic problems, typical problems philosophy teachers have to deal with in their teaching: 1) Given the limited time and the extensive content, the teacher must significantly reduce the subject, and can only present the most important aspects of philosophy. 2) Philosophy can have several purposes, with intrinsic and utility-oriented purposes being the most important dividing line. 3) There are different views on whether it is worth teaching the history of philosophy, because there are several risks, but some teachers still think it is important. 4) Philosophy teachers and many philosophy students have different views on argumentation. For the teachers, argumentation is a tool for thinking in philosophy, while the students express a more rhetorically oriented view of argumentation. 5) Teaching independence in philosophy seems to be particularly difficult, several teachers describe that it is something that must be developed from within the student. 6) Several teachers perceive that students today often are opinion-relativistic oriented, which is partially confirmed by the fact that the students in the survey support an opinion-relativistic statement.
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Elucidation of mechanisms in modulation of signaling by transforming growth factor-β (TGF-β) in breast cancer
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540435
The cytokine transforming growth factor-β (TGF-β) is overexpressed in most advanced solid cancers, and it has a biphasic role in tumor progres-sion. Initially, TGF-β acts as a tumor suppressor since it inhibits the prolif-eration and promotes apoptosis of most cell types. However, in advanced cancers, TGF-β acts as a tumor promoter, which includes effects on the tumor cells, e.g. promotion of epithelial-mesenchymal transition (EMT), which is connected with increased invasiveness and metastasis, as well as effects on non-tumor cells.
Breast cancer, the most commonly diagnosed cancer in women. Given the importance of TGF-β in regulating both tumor suppression and promotion, understanding its precise role in breast cancer could offer new opportunities for therapeutic intervention, particularly in developing treatments that can selectively block the tumor-promoting effects of TGF-β without disrupting its normal physiological functions.
In this study, we explored the mechanisms by which the transcription factor ΔNp63, the epigenetic regulator chromodomain helicase DNA binding protein 4 (CHD4), the Rho-associated coiled-coil-containing protein kinases (ROCK1 and ROCK2), and integrin-αvβ5, influence TGF-β signaling and how these factors contribute to breast cancer progression.
Paper I demonstrated that TGF-β, through the activation of SMAD2/3, leads to the dissociation of ΔNp63 from the NURD or NCOR/SMRT histone deacetylation complexes. while promoting the formation of ΔNp63-p300 complexes, which alters histone acetylation levels and affects ΔNp63-dependent transcriptional outcomes.
Paper II showed that ROCK1 and ROCK2 have opposing effects on TGF-β-SMAD3/4 transcriptional activity. ROCK1 inhibits, while ROCK2 stimulates this activity, both in a kinase-dependent manner. Consistent with these findings, depletion of ROCK1 enhances TGF-β-induced invasion in breast cancer cells, whereas ROCK2 depletion reduces invasion.
Paper III revealed that CHD4 knock-out significantly increases CAGA12-GFP activity in MDA-MB-231 cells, with similar results observed in other breast cancer subtypes, underscoring the broad relevance of this finding. CHD4 is primarily localized in the nucleus and interacted with SMAD3, to a lesser extent with SMAD2, but not with SMAD4, in a ligand-dependent manner.
Paper IV demonstrated that integrin-αvβ5 facilitates the activation of the MEK-ERK MAPK pathway, which in turn promotes the expression of AP-1 components, particularly FOS family members. This enhances the expression of a subset of TGF-β-inducible genes associated with migration and invasion, including LAMB3, WNT7B, MMP9, and IL-11.
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Inhibition of Insulin-regulated aminopeptidase in the brain : Evaluation of cognitive markers and restorative effects
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540183
Cognitive functions like learning and memory, are natural abilities that humans are highly dependent on to function properly. Neurological disorders like dementia, ischemia, and substance-use disorder may all severely impair cognitive functions. The complexity of the brain and its neurobiology make it challenging to develop potent new therapies that can prevent the onset of disease or relieve symptoms. Few new drugs have been successful in the last decades, thus new targets are wanted. In 1995, a new aminopeptidase member was discovered in fat and muscle cells, the insulin-regulated aminopeptidase (IRAP). IRAP is expressed in many different tissues, including several regions of the brain associated with cognition. The endogenous hexapeptide angiotensin IV (AngIV) and similar ligands binds to IRAP, and causes inhibition of its enzymatic activity. This inhibitory intervention is suggested to improve cognitive functions.
The overall aim of the present thesis was to investigate the effects of inhibiting IRAP in the brain. The project has focused on studying restorative effects, cognitive markers, and effects on memory performance using the synthetic IRAP inhibitors HA08 and compound 9 (C9). These two IRAP inhibitors improved cellular function in damaged primary neuronal cultures, an effect that was more prominent in hippocampal cell cultures. The difference in effect between hippocampus and cortical cell cultures may be linked to the composition of cell types and the expression pattern of IRAP in these regions. C9 was also demonstrated to have positive effects on drebrin expression, a protein highly concentrated in dendritic spines. Furthermore, C9 regulated the distribution of microtubule-associated protein 2 (MAP2) positive neurons and glial fibrillary acidic protein (GFAP) positive astrocytes, key markers for improved synaptic activity and cognitive functions, in primary neuronal cultures. Although many positive results were obtained from the in vitro studies, behavioural studies on male rats did, however, not demonstrate any effects on memory performance after an acute HA08 administration.
In conclusion, the findings in the present thesis confirm that IRAP-inhibition can induce positive effects on cellular health, and increase the expression of proteins important for synaptic plasticity. These results further indicate that IRAP may be involved in cognitive mechanisms, and strengthens IRAP as a potential target for treatment of different neurological diseases.