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Recent Submissions
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(2024)Degeneration of dopaminergic neurons in the substantia nigra is a primary pathological feature of Parkinson’s disease (PD). Current treatment strategies available are not disease-modifying but rather symptom-alleviating due to limitations in understanding the molecular event(s) that trigger the degeneration of dopaminergic neurons. While several animal and cellular models exist to study the disease progression and pathophysiology, their translational relevance to humans is debatable. In this thesis, our goal was to replicate a published protocol designed to differentiate SH-SY5Y human neuroblastoma cell lines into dopaminergic neurons. Our study shows successful differentiation and characterization of SH-SY5Y cells into dopaminergic neurons, but also the limitations in reproducibility. This finding highlights the challenges of technical variability, but also the reliability of existing protocols by emphasizing the need for more consistent reproducible methods as it could be significant for improving this cellular model.
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(2024)Aging is characterized by a gradual decline in cellular functions and the emergence of various cellular phenotypes that negatively affect lifespan. However, the molecular mechanisms behind these aging phenotypes remain unclear. One potential factor is the decline in proteostasis, characterized by increased protein misfolding and reduced efficiency of the proteostasis network. A key regulator of this network is Heat shock protein 90 (Hsp90), a molecular chaperone that ensures the proper folding and stability of hundreds of client proteins. Many of these clients are metastable signal transduction and gene expression regulators, such as kinases and transcription factors. By controlling the functional conformation of its clients, Hsp90 plays a central role in modulating the activities of many cellular processes. During environmental stress conditions, when Hsp90's folding capacity is exceeded, new phenotypes arise due to the altered folding of Hsp90 clients. I hypothesize that the age-related rise in protein misfolding similarly limits Hsp90’s availability to assist in the folding of client proteins, resulting in the emergence of aging phenotypes. To address this, I investigated whether Hsp90's functional capacity declines with age and how this decline is linked to proteome alterations and consequent phenotypic changes. To assess how Hsp90 function changes with age I utilized a β-galactosidase-based Hsp90 availability reporter. Measurements in young and aged cells demonstrate that Hsp90 activity declines with age. To assess the consequences of Hsp90's functional decline on the proteome of aged cells I employed quantitative proteomics. Results identified Hsp90-sensitive targets associated with cell cycle regulation, supporting previous findings linking Hsp90 inhibition with cell cycle defects and cellular elongation. Indeed, the progeny of aged mother cells exhibited elongated phenotypes compared to the progeny of young cells, but this trait was restored by Hsp90 overexpression. Furthermore, high-level expression of an exogenous Hsp90 client, a glucocorticoid receptor, which competes for Hsp90 availability, exacerbated elongation effects even in young cells. Altogether, these findings suggest that the availability of Hsp90 declines with age, correlating with the onset of aging phenotypes due to changes in the client proteome. Given Hsp90's role in suppressing cellular senescence in myoblasts and its association with brain aging and neurodegenerative diseases, these insights may have broader implications for understanding the emergence of aging phenotypes at a molecular level.
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(2024)Epilepsia on sairaus, joka ilmenee suurentuneena riskinä saada epileptisiä kohtauksia pitkällä aikavälillä. Tässä tutkielmassa selvitettiin, kuinka moni tutkimukseen otetuista potilaista sai epilepsiadiagnoosin ja näistä diagnooseista selvitettiin epilepsioiden etiologiat. Tutkittiin myös anamneesin tietojen ja tutkimustulosten yhteyttä epilepsian kehittymiseen. Tämän retrospektiivisen tutkimuksen potilaat olivat tulleet EEG-tutkimukseen Helsingin Uuteen lastensairaalaan ensikohtauksen tai kohtausepäilyn takia. Anamneesin tietojen ja tutkimustulosten yhteyttä arvioitiin khiin neliötestillä ja iän yhteyttä arvioitiin kahden riippumattoman otoksen t-testillä. Tutkimukseen otettiin mukaan 478 potilasta ja 115 näistä potilaista sai epilepsiadiagnoosin seuranta-aikana. Kehittyneistä epilepsioista geneettiset ja rakenteelliset syyt aiheuttivat suurimman osan epilepsioista. Varma epileptinen kohtausoire, akuutti altistava tekijä, akuuttilääkityksen tarve, neurologinen perussairaus, epänormaali EEG, piikit tai purkaukset EEG:ssä ja EEG:n aikainen epileptinen kohtaus olivat tilastollisesti merkittäviä epilepsian kehittymiselle. Epilepsiaan sairastuneet potilaat olivat keskimäärin vanhempia kuin ne, jotka eivät sairastuneet. Potilaille kehittyneiden epilepsiamuotojen jakauma eroaa maailmanlaajuisesta jakaumasta, mutta käytetyt tutkimusmenetelmät ja tutkimukseen sijainti selittävät paljolti tämän eron. Muut samasta aiheesta tehdyt tutkimukset tukevat tämän tutkimuksen tuloksia epilepsian riskiä kasvattavista tekijöistä. Yksikään näistä tekijöistä ei kuitenkaan ole varma viite epilepsian kehittymiselle.
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(2024)Aim: A low Glasgow Coma Scale Score (GCS) on admission is a known predictor of poor outcome from childhood bacterial meningitis. In turn, the factors associated with the admission GCS are less known. Our aim was to identify them, both for clinical alerts of reserved prognosis and to find potential targets for intervention. Methods: This study is a secondary analysis of data collected prospectively in Angola and in Latin America between 1996 and 2007. Children with bacterial meningitis were examined on hospital admission and their GCS assessed using the age-adjusted scale. Associations between on-admission GCS and host clinical factors were examined. Results: A total of 1376 patients with confirmed bacterial meningitis were included in the analysis (609 from Latin America and 767 from Angola). Median GCS was 13 for all patients (12 in Angola and 13 in Latin America). In the multivariate analysis, in the areas combined, seizures, focal neurological signs, and pneumococcal etiology associated with GCS <13, as did treatment delay in Latin America. Conclusion: Besides pneumococcal etiology, we identified characteristics, easily registrable on admission, which associated with a low GCS in childhood bacterial meningitis. Of these, expanding pneumococcal vaccinations and treatment delay could be modified.
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(2024)Aims. Bilingual children might differ from monolinguals in learning to read and write according to previous research. The ability to read and write enables people to learn new things and allows for diverse participation in society. Bilingual children’s reading and writing difficulties can be more challenging to recognize and assess, and therefore it is important to understand the typical development in bilinguals. The differences in reading skills between monolingual and bilingual children have not been extensively researched. The purpose of this study is to examine the differences between monolingual and bilingual children’s reading and writing skills and also identify the underlying linguistic factors associated with them. Assessing linguistic factors related to reading has been found to predict reading and writing difficulties making an early intervention possible. This study also aims to explore the gender gap in reading considering the recent studies that highlight growing differences between boys’ and girls’ reading outcomes during Finnish comprehensive school. Methods. The participants (N = 371) were 3rd grade students who had acquired Finnish (n = 107), Swedish (n = 144) or both Finnish and Swedish (n = 120) as their native languages. Reading and spelling skills were assessed with real word, pseudoword and text reading fluency tasks, a dictation task and a reading comprehension task. Additionally, the relationships between linguistic factors and reading and writing tasks were examined with receptive vocabulary task and objects and letters rapid automatized naming (RAN) tasks. The data was analyzed using IBM Statistics SPSS 28 -program and the differences between language and gender groups were compared using T-test or its non-parametric counterpart Mann-Whitney U -test. The relationships between linguistic factors and reading and writing tasks were explored using linear regression models. Results and discussion. The main outcome of this study was that bilingual students who had acquired Finnish and Swedish as their native languages performed at least as well as monolingual students with Swedish as their native language when both groups were assessed in their language of schooling, Swedish. Additionally, bilingual students achieved statistically significantly better scores than monolingual students in pseudoword reading fluency. The results concerning the gender gap partially deviated from previous studies since monolingual Swedish-speaking boys scored statistically significantly higher than girls in pseudoword and text reading fluency. Bilingual girls’ performance was in line with prior research, as they performed better than boys in reading comprehension. The relationship between receptive vocabulary and all reading and writing tasks was found to be statistically significant in every language group, while objects and letters rapid automatized naming (RAN) showed varying relationships with reading and writing in all language groups. More research is needed to study how simultaneous bilingual children learn to read and write in both of their languages.