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Huntington's disease (HD) is a progressive neurodegenerative disorder that causes involuntary muscle movements, deteriorates muscle coordination and cognitive decline. Typical onset age of the disease is in mid age, although a juvenile form of HD is also known. The disease is inherited in an autosomal dominant manner via a mutation in the huntingtin gene (HTT). The characteristic mutation in HTT is an expansion of the glutamine stretch at the 5 end of the gene. Excessive amounts of glutamine residues alters the conformation and chemical features of the huntingtin protein (HTT) leading to accumulation of cellular aggregates. Although to date there are several known alterations in the cell that contribute to the disease, the pathogenesis of HD is not fully understood. Ubiquitin proteasome system (UPS) dismantles proteolytically unneeded or damaged proteins, which are targeted to proteolysis when ubiquitin tags are added to them. Deubiquitinating enzymes (DUB) recycle ubiquitin molecules by releasing them from proteasome substrates. Recycling of ubiquitin is critical to a cell as it maintains the free pool of the targeting molecule. Ubiquitin-specific protease 14 (USP14) is one of the DUB family enzymes and its distinctive function is to remove ubiquitin molecules from the tip of the ubiquitin chain and thus antagonize protein degradation. Although the specific function of the protein is unclear, it seems that USP14 operates as a fine regulator of protein turnover rate and in ER stress both in catalytic and non catalytic manner. The role of USP14 is especially emphasized in the nervous system, as it regulates synaptic transmission and neuronal development. Although it is suggested that dysfunction of UPS is involved in the pathogenesis of HD, the role of USP14 in the disease remains to be unknown. IU1 is a novel inhibitor of the catalytic domain of USP14. Studies with IU1 indicate that inhibition of USP14 enhances the clearance of aggregate prone proteins. The approach of this thesis was aimed to elucidate the routes of HD pathogenesis from diverse approaches. The general aim of the thesis was to investigate the role of USP14 in the wild-type PC6.3 cell model, and in the pathogenesis of HD by expressing HTT proteins with different lengths of glutamine stretches in PC6.3 cells. The specific aim of the study was to examine by western blot and microscopy analysis the pathogenic routes of HD that involve ER stress, oxidative stress, autophagy and mutant HTT aggregate dynamics. The function of USP14 was studied with overexpression of USP14, or by inhibiting its catalytic activity by IU1. The findings of this thesis show that overexpression of USP14 enhances the clearance of mutant HTT aggregates, and this effect is obtained in catalytic activity dependent manner. I show that upregulated USP14 is connected to improved clearance of mutant HTT and inhibition of autophagy, suggesting that the degradation is mediated via UPS. The catalytic activity of USP14 might also be important in ER stress regulation, as the results indicate that IU1 activates phosphorylation of both JNK and eIF2α. I was also able to establish a connection between USP14 and GADD34, as I show that GADD34 upregulates USP14. Finally, I show that catalytic inhibition of USP14 decreases the expression of antioxidant SOD2. The data in this thesis is lacking statistical significance, and it can be considered solely as a guideline. However, together these results indicate that the deubiquitinating activity of USP14 increases survival in PC6.3 cells in both a healthy and a HD model.

High-grade Serous Cancer (HGSC) stands out as the most prevalent and lethal subtype of ovarian cancer, characterized by genomic instability and aggressive behaviour. Genetic alterations are pivotal in its development and progression, which leads to distinct molecular profiles and clinical behaviours. Recent attention has shifted towards understanding the influence of Tumour Microenvironment (TME) in cancer prognosis. This study aims to uncover the relationship between TME, molecular profiles, and clinical outcomes in HGSC. To achieve this, Random Forest (RF) analysis on single-cell and spatially resolved data from high-plex immunofluorescent images was employed. By leveraging RF's feature selection capabilities, we identified pertinent TME features associated with the clinico-molecular characteristics of HGSC. Our analysis revealed distinctive TME characteristics in HGSC patients with BRCA loss and homologous recombination repair proficiency. Notably, we found that Major Histocompatibility Complex (MHC) class II expression, originating from cancer cells, was a critical feature that shaped the immune environment and cancer behaviour. Moreover, we discovered that MHC molecules, specifically MHC-II, were also crucial in distinguishing short and long-term survival groups. Increased MHC-II expression was associated with improved survival, independently of molecular profiles. This association highlighted the importance of endogenous immunity in fighting cancer. In conclusion, MHC-II is a crucial prognostic marker in our study, offering a valuable and assessable metric for patient prognosis. In addition, the identification of phenotypically distinct survival groups based on TME characteristics underscores the potential of our approach in enhancing patient stratification and guiding personalized treatment strategies, ultimately improving the management of HGSC.

Study-related burnout is a growing problem among university students. Study-related burnout is defined by exhaustion related to studying, a cynical attitude towards studying and feelings of inadequacy. Burnout can be caused by an overtaxing workload and by a lack of personal, social, or material resources. Stress is a natural part of life, but chronic stress can lead to illness and burnout. Students experience stress in their studies and interventions aiming to reduce stress and prevent burnout are therefore necessary. Psychological flexibility increases wellbeing and prevents burnout and is also related to enhanced learning. Acceptance and Commitment Therapy (ACT) is focused on improving psychological flexibility. Good study skills can also prevent burnout. The aim of this study was to examine university students’ experiences of an online ACT-based intervention that aims to increase psychological flexibility and enhance wellbeing and learning. The aim was also to compare the experiences of two groups of students based on their change in study-related burnout during the course. The participants wrote reflective diaries that were qualitatively analyzed using inductive category development and categories that describe students’ experiences of the intervention were formed. The result of this study shows that students had benefited from the course and described effects on both wellbeing and learning. Students in both study groups experienced effects on wellbeing and learning. The importance of peer-support during studying was discussed, which highlights the need for support from peers who experience similar difficulties and concerns. There were also mentions of negative experiences which the students gave as explanations to why a part of the course had not been effective in enhancing their wellbeing and learning. These categories were more often discussed by students whose risk for burnout had increased during the course. Several categories under the themes of positive experiences of effects on wellbeing and learning were more often discussed by students whose risk for burnout had decreased during the course. The result of this study shows that the ACT-based intervention can be regarded as effective in improving wellbeing and studying, and experiences of the intervention were in general positive. Integration of similar interventions in study programs would be beneficial.

As part of the European Green Deal, the European Union has set a goal to increase its domestic raw material extraction by 2030. The EU Critical Raw Materials Act lays out concrete goals for securing and strengthening EU’s domestic supply of critical raw materials. The Critical Raw Materials Act will potentially have significant impacts on land use in Europe’s mineral rich regions. These include northern Fennoscandia which is also home to the Indigenous Sámi inhabiting Sápmi. Extractive projects have multifaceted impacts on local communities and the environment, and mining-related conflicts are on the rise globally. The EU’s goal to increase mining domestically calls for the critical assessment of mining from the perspective of justice. The theoretical framework of this thesis comprises of environmental justice and extractivism. The geographical focus of this thesis is on mining in the northern parts of Fennoscandia – Norway, Sweden and Finland. My research question is: how do different stakeholders from Norway, Sweden and Finland view increasing mining in northern Fennoscandia from an environmental justice perspective? My method is critical discourse analysis consisting of three levels of analysing discourse: textual, interpretative, and critical. I combine perspectives of environmental justice to the study of discourse and apply an environmental justice framework consisting of procedural, recognition and epistemic justice. My data consists of stakeholder feedback submitted to the European Commission’s open online consultation on the Critical Raw Materials Act proposal. The aim is to understand how different stakeholders consider environmental justice aspects as part of increasing extractive activities in northern Fennoscandia. The analysis reveals that most stakeholders agree with the need to increase mining of critical raw materials, and the northernmost Fennoscandia is coined as an important location for mining critical raw materials. Regions emphasize the involvement of local communities and the positive contributions of mining locally. Sámi representatives underline Indigenous rights and strengthening Sámi participation in decision-making. Business actors emphasize the need to accelerate mining permitting processes and to reassess environmental legislation in the context of mining projects. Many stakeholders view technological solutions as a means to conduct mining sustainably, and business actors in particular call for a change of attitudes towards mining. A critical analysis reveals that in terms of environmental justice the discourse is rather limiting; local and traditional knowledge and livelihoods are not thoroughly addressed, and the environment is viewed mainly as a resource.

Clonal hematopoiesis is characterized by the accumulation of blood cells originating from a single mutated hematopoietic stem cell clone. Clonal hematopoiesis has been hypothesized to contribute to systemic inflammation, and by doing so increase the risk for inflammatory diseases. Despite the growing body of evidence from clinical datasets and murine levels linking clonal hematopoiesis and inflammation, the causative role of clonal hematopoiesis in promoting inflammation remains to be fully elucidated. The primary goal of this master's thesis is to investigate the potential causative relationship between clonal hematopoiesis (CH) and rheumatoid arthritis, one of the most common autoimmune diseases previously associated with clonal hematopoiesis. The analysis is done primarily by employing Mendelian randomization (MR) and multivariate logistic regression analyses to perform two-sample Mendelian randomization in a bidirectional manner to assess the strength of the analysis along with exploring potential pleiotropy. We leverage data from two large population-level cohorts: the FinnGen study and the UK Biobank project. We also employed multivariate logistic regression to validate the instrumental variables of the UK Biobank within the FinnGen data. Despite prior epidemiological and functional literature linking clonal hematopoiesis and rheumatoid arthritis, we observed no association between these two in these large-scale Mendelian randomization analyses. This may be due to differences in cohort characteristics and detection methods for clonal hematopoiesis between the two cohorts. The thesis discusses the strengths and weaknesses of Mendelian randomization in evaluating causative links between human phenotypes. This work contributes to the growing area of research on the genetic determinants of inflammatory diseases and opens avenues for further research into the role of CH in disease pathogenesis

The aim of the study was to explore the impact of commuting and location of the residence on a consumer's total emission of greenhouse gases. The subject was chosen because many Finns move to a dwelling that is situated far away from their place of work. The research questions were: 1. How big a proportion of the total emission of consumers' greenhouse gases is due to the passenger traffic? 2. What would be the increase of greenhouse gas emission if an employee moved from Helsinki (Finland's capital city) to Nurmijärvi (a municipality located 37 km from Helsinki) assuming that the employee works in Helsinki and the commuting mode is switched from the metro to a private car. (There is no metro nor train connection between Helsinki and Nurmijärvi.) Passenger traffic forms with its estimated 33% the biggest source of consumption caused greenhouse gas emissions in Finland. Private car use is the main source of greenhouse gas emissions deriving from passenger traffic. If an employee moved to an electrically heated single-family house located about 40 km from the place of work the emission rate would increase by 75% assuming that the commuting mode is switched from the metro to a private car. Most of the increase would be due to the change of commuting mode. Most public transport in Helsinki takes place by rail (metro, tram, and train). Metro is the most favorable transportation mode in regard to greenhouse gas emission. Automobiles are the most damaging commuting alternative. A car with driver and no passengers on a motorway emits about 8 times more greenhouse gas (21.84 kg per 100 km or 62.5 miles) than travel by metro in Helsinki (2.87 kg per 100 km or 62.5 miles). A car moving in city streets emits about 10 times more greenhouse gas (27.3 kg per 100 km or 62.5 miles) than does metro travel. Substituting diesel for gasoline reduces emissions by very little. The use of diesel on a motorway decreases emissions by only 7% whereas diesel driving in a city increases emissions by 4%. Travel distances between home and work in Finland increased by about 80% between 1980 and 2003. In the same period the number of private cars increased by 86% and kilometers driven per year per car increased by 92%. The results are based on statistics and calculations based on these statistics concerning traffic, housing, heating, and electrical use. Also previous studies dealing with residential sprawl, traffic, energy production, and greenhouse gas emissions produced by Finnish consumers were referred to.

Since the establishment of pathologic and cytogenetic laboratories, left-over material in the form of G-banded slides and cytogenetic fixed cells, as well as formalin-fixed, paraffin-embedded (FFPE) material, tissue samples, blood and bone marrow have been stored in archives for possible later reference. This material, which potentially contains rare and special cases, has been a welcome source for retrospective studies or e.g. for trying out new methods of analysis. Molecular genetic and molecular cytogenetic techniques such as Southern hybridization, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) have been successfully applied on different kinds of archival specimens. With this study we wanted to explore, both through a literature review and through a practical experiment, the history, present day and future use of such archival material in the light of molecular cytogenetics, including the challenges of DNA extraction, sample degradation, data analysis and interpretation as well as ethical issues. The experimental part had two main objectives, (1) to investigate the use of archived cytogenetic material in the form of G-banded slides and cytogenetic fixed cells for array-based CGH (aCGH), and (2) to explore abnormalities on chromosome 1q in hematologic malignancies. Extra material on the long arm of chromosome 1 is a common recurrent chromosomal abnormality that is present in many classes of hematologic cancers as either primary or secondary aberration. It is the most common structural aberration in multiple myeloma (MM), myeloproliferative disease (MPD) and myelodysplastic syndrome (MDS) and is also a frequent aberration in pediatric acute lymphoblastic leukemia (ALL). It has been associated with increased cell proliferation, disease progression and poor outcome, the mechanisms of which are not fully understood yet. To combine these two aims, we screened the patient database for relevant cases and searched the archive for corresponding samples. The idea was to find cases of hematologic malignancies with extra material on chromosome 1q that were available as cytogenetic slides, fixed cells and frozen bone marrow, find an ideal method of DNA extraction from slides (for other material ready protocols were available), analyze the samples with aCGH and compare the results. We wanted to prove the eligibility of archived cytogenetic material for aCGH analysis and at the same time study rearrangements of 1q in our samples. Starting with 38 patient cases, DNA extraction was performed with 2 different protocols, the latter of which, using a modified version of the Puregene® DNA Purification Kit Protocol for Blood Smears, turned out to be more successful. After having obtained sufficient DNA from several slide samples, we assessed DNA quality with agarose gel electrophoresis. Because slide DNA was too fragmented to be used for aCGH and whole genome amplification (WGA) was not a choice, the experiment was continued with archived fixed cells, bone marrow and archived DNA only. Using a high resolution 60-mer oligonucleotide 44K human CGH microarray platform, we analyzed 15 patient cases that were available both as fixed cell and DNA samples (2 cases), both as fixed cell and bone marrow samples (1 case), both as fixed cell and CPT™ cell samples (1 case), frozen bone marrow (7 cases) and DNA samples (4 cases). The malignancies were pediatric ALL (6 cases), adult ALL (1 case), chronic myeloid leukemia (CML, 2 cases), non-Hodgkin lymphoma (NHL, 1 case), Burkitt lymphoma (BL, 3 cases), Hodgkin's disease (HD, 1 case) and one undefined malignancy. After analysis with CGH Analytics software, we saw that aCGH results of fixed cells compared to results from bone marrow or DNA were almost identical, which confirmed that cytogenetic fixed cells were a reliable source for aCGH analysis. Challenges of working with archived material were witnessed in the form of CG-waves and centralization errors and deviations of the hybridization ratio diagram caused by partially degraded DNA. Concerning aberrations calls, 12 of the 15 cases had detectable aberrations on 1q, which included amplification of the whole 1q arm (1 pediatric ALL, 3 BL cases) and duplications or amplifications of parts of 1q (5 pediatric ALL, 2 CML and 1 undefined malignancy cases) in addition to other aberrations. Common break points were 1q21.2 (2 CML cases), 1q23.2 (1 pediatric ALL and 1 CML case) and 1q32.3 (2 pediatric ALL cases), and we detected 2 large common overlapping areas, at 1q21.2q23.2 and 1q25.3q32.2. The areas were, however, too vast for disease gene screening, spanning several Mb each. We could thus prove and confirm the value of cytogenetic archives for scientific studies. Array CGH with fixed cells was confirmed to work well, also frozen bone marrow and archived DNA were valuable sources. We would suggest further aCGH experiments with cytogenetic slides by applying WGA but would also suggest slide and fixed cell material to be used for Next Generation Sequencing, which has not been reported yet. Regarding aberrations on 1q, further studies to more accurately delimit relevant break points and common overlapping areas are recommended.

Vegetation maps and bioclimatic zone classifications communicate the vegetation of an area and are used to explain how the environment regulates the occurrence of plants on large scales. Many practises and methods for dividing the world's vegetation into smaller entities have been presented. Climatic parameters, floristic characteristics, or edaphic features have been relied upon as decisive factors, and plant species have been used as indicators for vegetation types or zones. Systems depicting vegetation patterns that mainly reflect climatic variation are termed 'bioclimatic' vegetation maps. Based on these it has been judged logical to deduce that plants moved between corresponding bioclimatic areas should thrive in the target location, whereas plants moved from a different zone should languish. This principle is routinely applied in forestry and horticulture but actual tests of the validity of bioclimatic maps in this sense seem scanty. In this study I tested the Finnish bioclimatic vegetation zone system (BZS). Relying on the plant collection of Helsinki University Botanic Garden's Kumpula collection, which according to the BZS is situated at the northern limit of the hemiboreal zone, I aimed to test how the plants' survival depends on their provenance. My expectation was that plants from the hemiboreal or southern boreal zones should do best in Kumpula, whereas plants from more southern and more northern zones should show progressively lower survival probabilities. I estimated probability of survival using collection database information of plant accessions of known wild origin grown in Kumpula since the mid 1990s, and logistic regression models. The total number of accessions I included in the analyses was 494. Because of problems with some accessions I chose to separately analyse a subset of the complete data, which included 379 accessions. I also analysed different growth forms separately in order to identify differences in probability of survival due to different life strategies. In most analyses accessions of temperate and hemiarctic origin showed lower survival probability than those originating from any of the boreal subzones, which among them exhibited rather evenly high probabilities. Exceptionally mild and wet winters during the study period may have killed off hemiarctic plants. Some winters may have been too harsh for temperate accessions. Trees behaved differently: they showed an almost steadily increasing survival probability from temperate to northern boreal origins. Various factors that could not be controlled for may have affected the results, some of which were difficult to interpret. This was the case in particular with herbs, for which the reliability of the analysis suffered because of difficulties in managing their curatorial data. In all, the results gave some support to the BZS, and especially its hierarchical zonation. However, I question the validity of the formulation of the hypothesis I tested since it may not be entirely justified by the BZS, which was designed for intercontinental comparison of vegetation zones, but not specifically for transcontinental provenance trials. I conclude that botanic gardens should pay due attention to information management and curational practices to ensure the widest possible applicability of their plant collections.

The interactions within plankton communities are complex, and realistic modelling of these interactions create a challenge in large-scale environmental models. The objective of this thesis was to evaluate whether Bayesian networks could be a suitable method in the modelling of these communities. Besides observing the interactions between different groups within phyto- and zooplankton communities, another goal was to focus on the potential change on the ecosystem level. To achieve this, dynamic Bayesian networks with hidden variables were used to observe whether structural changes in plankton communities could reveal larger trends in the aquatic ecosystem. To compare performance and accuracy of the model, two Bayesian food webs with differing causal links between observations were built. Of the two models, the simpler construct utilizing hidden Markov model fared better, and a clear trend was detected in the hidden variable. This trend in the time series signify that the relationships between the observed variables have changed during the study period. The plankton data set was collected from the Archipelago Sea between 1991 and 2016 and the results from the model were further analyzed alongside with this observational plankton data. In the samples the total biomass of phytoplankton grew throughout the study period, whereas at the same time the total biomass of zooplankton declined. As the Bayesian network considers the observable variables while maximizing the fit of the hidden variable, the observed trend in the hidden variable indicate that some unobservable variables are affecting both phyto- and zooplankton communities. This clear trend detected by the hidden variable might be related to a trend of increasing eutrophication in the study area, but to better understand the drivers causing this change further research is needed. Besides detecting underlying trends, the dynamic Bayesian networks are a promising method to study the interactions within plankton communities.

Marine heatwaves (MHWs) are distinct periods of elevated water temperature. They have been shown to affect benthic ecosystems and their frequency is expected to increase as a result of climate change. I studied the effects of MHWs on benthic infauna communities across a vegetation gradient to find possible species- and size-specific as well as habitat dependent changes related to the elevated temperatures. This was done via the newly developed Hotfloor system in which benthic chambers are used to heat the sediment in situ. There were 10 heated chambers and 10 control chambers used across the vegetation gradient. For both treatments, 4 chambers were placed in bare sediment, 3 chambers in sparse vegetation and 3 chambers in dense vegetation. In addition to the chambers, I also sampled the benthic fauna in natural start conditions in the same vegetation categories as a baseline. All sampling was done in situ via scuba diving. The results indicate that vegetation cover protects infauna from MHWs as in the bare and sparse categories the decline in abundance and increase in biomass was clearer than in the dense vegetation. The decreasing abundance results from increased mortality and the increasing average biomass implies that the surviving individuals are of larger size. The decrease in abundance of juveniles and smaller individuals was also clear from the size structures of Macoma balthica which is a key species in the benthic ecosystems of the Baltic Sea. Despite the increased mortality, the species compositions remained relatively similar, and the same species dominated in both the heated and control treatments. This means that the ecosystem functioning was retained after the heatwave, even though MHWs did lead to lower abundances and thus less resilient ecosystems. Further research on the long-term impacts of MHWs is needed to fully understand how these ecosystems can change in the future when MHWs are predicted to become even more severe and frequent.