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Carbon capture and storage may become an inevitable means in mitigating climate change. However, it is a new technology involving a great deal of uncertainties. It is of utmost importance to understand on one hand, the risks caused by the technology and on the other, what is holding it back. This way unforeseen setbacks and environmental or other damage could be avoided. This thesis is a part of a wider research project on the risk governance of carbon dioxide capture and storage (RICCS). The present study gives additional insights to CCS risk analysis by diving into the stories that the media tells about the risks. I analyze the media coverage on the risks of CCS in the most wide spread newspapers of Norway and Finland with the aim of identifying what kind of risk framings are portrayed by the media; how strong is the presence of uncertainties and what kind of uncertainties are brought up. The media is seen as a mirror of public perception, but also one of the players influencing it. The possible effects that the analyzed articles could have on public perception of risks are discussed. The theoretical framework consists of theories of systemic risks, narrative policy analysis and framing of environmental risks in the media. I describe the nature of systemic risks. Then I move on to framing, more specifically how environmental risks are framed in the media and how it can effect public perception. After this I explain how narrative analysis can be used as a tool for identifying framings. Then I describe Klinke and Renn's Prometheus theory that I will use for analyzing the level of uncertainty in the framing of the articles and for discussing the implications of my findings. The results show that the risks caused by CCS are mainly the lock-in in fossil fuels, it's possible negative effect on developing renewable energy and environmental and health risks in general. The risks towards successful CCS seem to be mainly connected to funding, which connects to emissions' prices, the climate agreement and viability of investments. The differences between the two countries are quite related to the situation in which each country is in terms of CCS development. Norway is very active and pushing CCS forward. Consequently, the Norwegian articles are generally not very critical of the technology itself, but discuss what is holding it back. Generally, the Finnish articles bring out more aspects on the issue, both positive and negative, leaving quite an ambiguous image to the reader. The implications of my findings for future policy practices are quite extensive and therefore not very useful, since most policy recommendations seem more or less relevant. What is interesting though, is that based on my findings I could identify the turning points in which public perception is most relevant. These are: What kind of energy production is supported? Is CCS an acceptable mitigation means? Is the risk of leakage taken as severe? These issues represent turning points for the future of CCS technology and deliberative processes can be crucial when discussing them.

Climate change severely threatens ecosystem services and human well-being: vegetation and soils underneath it can be particularly vulnerable to climate warming. Soils hold the largest carbon stock in terrestrial ecosystems, and urban park soils, especially in cool climates, can hold remarkable carbon stocks and may be able to offset some atmospheric CO2 emissions. Land use changes, such as urbanization, influence soil organic carbon formation and soil carbon storages. In this study, I was interested whether three vegetation types (deciduous trees, conifers and lawn) differ in their capacity to store C in their rhizosphere, and whether this is affected by park size. I measured the proportion of tree canopy layer in class A park areas of the city of Helsinki, to estimate soil C storages of these areas and to examine C density (kg C m-2). Proportions of tree canopy layers in different park size groups were measured using QGIS and ortographs. Soil C storages were calculated using existing soil C data and average proportions of conifer and deciduous trees in parks of the city of Helsinki. Park size had a significant effect on proportion of the tree canopy coverage: canopy cover decreases with an increase in park size. Especially large parks are dominated by lawn. The average soil C densities in small, medium and large parks were 23.98 kg C m-2, 23.47 kg C m-2 and 23.15 kg C m-2, respectively. However, the overall proportion of conifer canopy in parks of the city of Helsinki is rather small, resulting in small differences in C densities between different park size categories, despite significant differences in tree canopy coverage between the three size groups. Most of the stored soil C in parks of the city of Helsinki are under lawn, even though it is the least efficient of the three studied vegetation types (deciduous trees, conifers, lawn) in soil C sequestration. Within a park size category and at park level, large parks store the highest amount of carbon per park. Even so, at the city level, the total amount of carbon is highest in the small parks due to their high number. Conifer trees associate with improved C sequestration to soils compared to deciduous trees and lawn. Increasing the amount of conifer trees in urban parks thus likely increase the important C storages of these soils. Results of this study highlight the importance of the contribution of urban parks and especially conifer trees in carbon sequestration. Future research related to urban soil C sequestration and the effects of vegetation type and climatic conditions is needed to better understand soil C accumulation and how the C sequestration of urban park soils could be enhanced.

Physical fitness has declined during the last decades in adolescents. Furthermore, several studies have found a positive association between physical fitness and brain volume in adolescents, which is noteworthy since the adolescent brain undergoes substantial changes during growth and maturation. However, despite the importance of the cerebellum on adolescents' cognition and coordination, there remains a paucity of evidence on the associations between physical fitness and cerebellum characteristics. Thus, a cross-sectional approach was used to explore the relationship of cardiorespiratory fitness (CRF), power, speed-agility, coordination and overall neuromuscular performance index (NPI) with total gray matter (GM) volume of the cerebellum as well as lobules VI & VIIb, and crus I volume in 40 (22 girls; 18 boys) adolescents. Peak oxygen uptake (V̇O2peak) was measured by the maximal ramp test on a cycle ergometer, lower limb power was determined with standing long jump (SLJ), speed-agility was assessed with the 10 x 5-m shuttle-run test, upper limb coordination was determined with the Box and Block Test (BBT) and NPI was calculated as the sum of SLJ, BBT and shuttle-run z-values. Lean mass (LM) and body fat percentage (BF%) were measured using a bioelectrical impedance analysis. Cerebellum GM volume, lobules VI & VIIb, and crus I volumes were measured by magnetic resonance imaging (MRI). Results demonstrated that V̇O2peak/LM was negatively associated (β = -.045 P= .014) with cerebellum GM volume. No statistically significant associations were found between SLJ, shuttle-run, BBT scores or NPI and cerebellum characteristics in all participants. However, a poorer shuttle-run time was associated (β = -.363 P = .024) with smaller crus I volume in girls and V̇O2peak/LM was negatively associated (β = -.501 P = .031) with lobule VIIb volume in boys. These findings suggest that, in general, CRF and speed agility are associated with cerebellum characteristics in adolescents and there may be sex differences. The results extend our knowledge of the associations between physical fitness and brain volume, but more studies should be conducted to understand the relationship further.

Lymphangiogenesis is the process that leads to the formation of lymphatic vessels from pre-existing vessels. Vascular endothelial growth factor C (VEGF-C), the ma- jor lymphangiogenic growth factor, is produced as an inactive precursor and needs to be proteolytically processed into a mature form in order to activate its receptors VEGFR-3 and VEGFR-2. A deficiency of VEGF-C during embryonic lymphangiogenesis results in embryonic lethality due to the lack of lymphatic vasculature. Hennekam lymphangiectasia-lymphedema syndrome (OMIM 235510) is in a subset of patients associated with mutations in the collagen- and calcium-binding EGF domains 1 (CCBE1 ) gene. CCBE1 and VEGF-C act at the same stage during embryonic lymphangiogenesis and their deficiency results in similar lymphatic defects. The mechanism behind the lymphatic phenotype caused by CCBE1 mutations is un- known. The aim of this study was to investigate the potential link between VEGF-C and CCBE1 that could contribute to the lymphatic phenotype. In this study, 293T cells were used to observe the effect of CCBE1 on VEGF-C pro- cessing. The co-transfection of constructs coding for CCBE1 and VEGF-C showed processing of the inactive pro-VEGF-C into the active, mature form. However, this processing was efficient only in 293T cells. When CCBE1 from 293T supernatant was purified, A disintegrin and metalloproteinase with thrombospondin type 1 motif 3 (ADAMTS3) co-purified with CCBE1. The levels of pro-VEGF-C and active VEGF-C were monitored by immunoblotting or immunoprecipitating metabolically labeled supernatant with specific antibodies or receptors followed by autoradiography. The activity of the processed VEGF-C was verified by proliferation of Ba/F3 cells stably expressing VEGFR-3/EpoR or VEGFR-2/EpoR chimeras. Furthermore, a VEGFR-3 phosphorylation assay was performed in PAE (Porcine Aortic Endotheial) cells to study details of the CCBE1-mediated regulation of VEGF-C. We found that CCBE1 increases the proteolytic processing of pro-VEGF-C, thereby resulting in increased activity of VEGF-C. CCBE1 itself has no effect on VEGF-C activity but regulates VEGF-C by modulating the activity of the ADAMTS3 protease. We also found that both pro- and mature- VEGF-C can bind to VEGFR-3 but only mature form is able to induce VEGFR-3-mediated signaling. In addition to cleaving VEGF-C, ADAMTS3 was found to directly or indirectly mediate CCBE1 cleavage. The N-terminal amino acid sequence of the ADAMTS3-processed VEGF-C confirmed that ADAMTS3 is the protease responsible for the activation of VEGF-C by 293 cells. Hence, we have identified a mechanism that regulates VEGF-C activity. This mechanism suggests the possible use of CCBE1 as a therapeutic means to treat diseases that involve the lymphatic system.

Forest certification has been used as a tool to promote forestry responsibility towards sustainable forest management. Forest Stewardship Council (FSC) is one of the certification systems that is well recognised in Europe. Nevertheless, compared to other European countries, the number of FSC chain of custody (CoC) certifications in Finland is relatively low. Semi-structured interviews were conducted with six FSC CoC certified companies to explore their experiences towards implementing and maintaining the system in their companies. The sample group was comprised of wood and paper product industries in manufacturing and trading sectors. Thematic analysis of the interviews revealed the challenges companies encountered. The results indicated that there were eight types of challenges, including three internal and five external ones, hindering the development of FSC CoC certification in Finland. Internal challenges included competence, financial resources, and a lack of motivation to change. External challenges included insufficient marketing and demand, uncertain cost benefit, keen competitor programmes, limited supply, and long trademark approval time. Meanwhile, the relevant solutions these companies adopted to deal with the challenges were discussed. Since external challenges out-numbered internal ones, it seemed that certified companies are not able to tackle the existing challenges alone. Joint-effort among other actors in the forestry sector, for instance, the national authority, FSC national office, certification bodies are essential to influence the rate of certification uptake. Furthermore, participants discussed about the future development of FSC CoC certification system in Finland. Interviewees believed that the enactment of the EU Timber Regulation (EUTR) and the introduction of forest certification into national public procurement policy could positively impact the development of the system. The results of this study could be used as a reference for potential certificate users to prepare themselves for implementing FSC CoC certification system. In addition, the study could shed a light on the development of FSC in Finland in the future.

The changes in lake diatom assemblages as a response to climate warming over the past three decades were examined in 26 lakes across Northwestern Finnish Lapland using multivariate statistical techniques. The lakes are distributed along a steep climatic and vegetational gradient, covering three distinct vegetation zones spanning boreal coniferous forest, mountain birch woodland, and treeless tundra. Lakes were selected following a study realised by Weckström and Korhola in 2001, who had sampled the same lakes for surface-sediment diatom assemblages, physical, and chemical limnological variables. Climate data from the past 30 years was retrieved, showing a slow and steady yearly increase in temperature, with strong seasonal fluctuation and fall months experiencing the strongest warming. Surface sediment samples were taken from the lakes and their diatom communities analysed. A total of 185 diatom taxa representing 27 genera were recorded. Ordination techniques (DCA, CCA) at the genus and species level were performed to identify the main patterns of variation between diatom data from the original data set and the current study, and their relationship to environmental variables. Strong changes were recorded in four of the lakes with major shifts in dominant diatom species. Moderate changes were recorded in eight lakes, where dominance changes were recorded for a few species while the majority remained unchanged. The remaining 14 lakes did not show noticeable changes over the 30-year period. Changes observed in the studied lakes did not follow a widely observed pattern in northern Hemisphere lakes. The results indicate that while climate change is a driving factor behind changing lake dynamics with increasing temperatures and decreasing lake ice cover duration, it cannot be the only force responsible.

Background– The BCL-2 protein family members are major regulators of apoptosis, and the anti-apoptotic (pro-survival) members of the family is commonly targeted with BH3 mimetic drugs in haematological cancers. However, these treatments have not been very impactful when administered as single agents and they have long been investigated for combination therapy with other agents. Acute myeloid leukaemia (AML) is one of the difficult-to-cure haematological malignancies. A recently approved therapy for AML consists of the combinatorial administration of venetoclax (a selective BCL-2 inhibitor) and a DNA methyltransferase (DNMT) inhibitor such as azacitidine or decitabine. Although this novel therapy has shown promising clinical results, the majority of the patients still relapse under this treatment. These relapsed patients typically become highly resistant to treatment and have poor prognosis, emphasising the need for new effective drug combinations. Apart from BCL-2, other family members like BCL-xL and MCL1 are also common targets of BH3-mimetic drugs. This project thus aims to understand and characterise the resistance against BH3-mimetics and investigate new therapeutic approaches to overcome the challenges of resistance. Aims– This study aims (i) to characterise BH3-resistant AML cell lines for uncovering the mechanisms of drug resistance, and (ii) to identify possible combination treatment options for overcoming drug-resistance. Methods– Viability assays with Cell Titer Glo® (CTG) and Drug Sensitivity and Resistance Testing (DSRT). The long-term effectiveness of venetoclax, azacitidine and talazoparib (a PARP inhibitor) as single agents, double combinations and triple combination were investigated with Time-to-Progression (TTP) assay. For the resistant cell line models, underlying resistance mechanisms were assessed by checking protein expression of pro- and/or anti-apoptotic members of the BCL-2 family members with western blot (WB). Real-time quantitative PCR (RT-qPCR) and WB were carried out for transcriptional and translational expression analyses of certain DNA damage-associated genes in PARP inhibitor-resistant cell lines. Results– Drug screening with DSRT has revealed promising results for two combination treatments of a BCL-xL inhibitor (A-1331852) (i) with an Aurora kinase A inhibitor (alisertib) and (ii) with an MCL1 inhibitor (S63845) for BCL-xL inhibitor-resistant cells. WB analyses of BCL-2 family members showed translational upregulation of un-inhibited members of the anti-apoptotic proteins in BH3-mimetic-resistant cell lines. A venetoclax-resistant AML cell line showed increased levels of the DNA damage marker P-γ-H2Ax upon treatments containing venetoclax, as well as increased levels of cleaved-PARP1, indicating induction of apoptosis. RT-qPCR analyses revealed increased mRNA expression of PARP1 in two resistant cell lines, whereas no significant expression changes in other DNA repair mechanism genes on the transcriptional level. Conclusions– In BH3-mimetic-resistant AML cell lines, apoptosis is avoided through translational upregulation of un-inhibited anti-apoptotic members of the BCL-2 family, and this resistance can be countered by combination treatment for additional inhibition of the compensatory anti-apoptotic proteins. Venetoclax is still effective on cells resistant to it, by inducing DNA damage and sensitising these cells against inhibitors of the members of DNA repair pathway. The transcriptional upregulation of PARP1 and the increase in its auto-catalytic activity suggests the DNA damage-inducing effects of the triple combination treatment [Ven + Aza + Tal].

Over the past years sugar consumption has seen great increases worldwide, together with a rise in the prevalence of metabolic diseases. There is a growing need for a comprehensive characterisation of the genes involved in sugar metabolism, yet the mechanisms by which cells sense and respond to sugars in vivo have remained incompletely understood. Here, I analyse members of a protein family best known for their regulation of differentiation during development with regards to their role in sugar metabolism. The Hairy and Enhancer of Split (HES) protein family are a group of basic helix-loop-helix (bHLH) transcription factors that function as major downstream effectors of the Notch signalling pathway. In mammals, the HES proteins have mostly been studied for their role in cell differentiation, but HES1 has been implicated in metabolic control. Drosophila has several transcription factors belonging to the HES family, including Hairy and seven bHLH transcription factors located in the Enhancer of split complex (E(spl)-C). The E(spl)-C bHLH transcription factors display high homology and are considered to be genetically redundant, and therefore little is known about their individual functions. The other HES family members in Drosophila have not previously been linked to metabolic regulation, but Hairy has been shown to repress the tricarboxylic acid cycle. In light of the findings implicating HES1 and Hairy in the regulation of metabolism, I systematically investigated the role of the HES transcription factors in sugar metabolism. By using the GAL4/UAS system in Drosophila melanogaster, I knocked down gene expression of each of the family members, and raised the flies on diets varying in sugar content to identify possible sugar intolerance phenotypes. Here, I show that knockdown of one of the E(spl)-C bHLH genes led to severe sugar intolerance that affected both survival and organismal growth, but did not alter the levels of circulating carbohydrates and storage lipids as measured with colorimetric assays and lipid staining. Furthermore, I identify the tissues in which this transcription factor functions to provide sugar tolerance. Using analysis of publically available chromatin-immunoprecipitation sequencing data coupled with quantitative RT-PCR, I uncover mTOR target Thor/4E-BP as a putative target gene. Additionally, I show that Hairy is similarly required for complete sugar tolerance, but that the mechanism differs from the E(spl)-C bHLH transcription factor. Hairy binds to and positively regulates expression of genes involved in glycolysis and the pentose phosphate pathway, suggestive of a cooperation with earlier known regulators of sugar sensing. In conclusion, I have shown that only two HES family members are involved in the regulation of sugar metabolism and that their regulatory mechanisms are distinct, implying that the HES family members have more diverse roles than previously assumed.

The degree of neurogenesis in the adult hippocampal dentate gyrus (DG) is the center of the discussion in the field of adult neurogenesis. Although there is an on-going controversy, accumulating evidence suggests that the neural stem cells (NSCs) in the adult human DG are very few. The question remains open as to why there are so few NSCs in the adult human DG when compared with the rodent DG. In order to address these questions, it seems necessary to understand the developmental process of the NSCs in the adult human DG. In this thesis, the neural stem and progenitor cells in the fetal human DG are characterized. In addition to these findings, a semi-automatic method for counting and categorizing cells in their expressions of immunochemistry markers is developed.

Charcot-Marie-Tooth disease (CMT) is a collective name for inherited neuropathies affecting the peripheral nerves. CMT affects 1:2500 children and adults worldwide. The disease is genetically highly heterogeneous, and the pathogenic mechanisms are largely unknown. Thus far, there is no cure known for the Charcot-Marie-Tooth disease. Therefore, the study of the genetic factors involved in the disease and the understanding of the underlying molecular mechanisms will benefit the development of strategies to prevent or treat these diseases. In this thesis, a new candidate gene for CMT was investigated in patient fibroblasts. The novel gene variant was originally found at University of Helsinki in a pair of Finnish brothers with CMT; and in later examinations, in their affected family members. The gene encodes an ER calcium channel receptor that is responsible for Ca2+ release from the endoplasmic reticulum (ER) and plays an important role in the regulation of various cellular processes. In this thesis, I studied the effect of the variant in patient fibroblasts by Western blotting, quantitative reverse transcriptase PCR (RT-qPCR) and calcium imaging. I also knocked down the gene using siRNA in healthy fibroblasts to investigate if the loss of the receptor has a similar effect on calcium signaling as the patient variant. My results showed that siRNA treatment significantly decreased the targeted protein levels and delayed the ATP-evoked Ca2+ release from ER without profound effect on the amplitude of the release. Similar effects of the studied mutation were observed in one patient cell line, but not in the other. Patient cell line, which did not have alterations in the levels of the protein and Ca2+ release, had elevated levels of mRNA of the affected gene. The results suggest that the gene variant does not impair the total volume of the ATP-evoked Ca2+ release from ER. The possible effect of the studied mutation may be related to the decreased levels of the mutated protein, which at the functional level may affect the timing of total Ca2+ release from ER. However, the functional effect of the variant could not be confirmed with the fibroblast cells; further experiments are needed to clearly confirm the variant’s effect on calcium signaling.