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Epithelial cells line the surfaces of organs and tissues in a continuous and tightly packed manner, thereby functioning as a protective barrier between the tissue and the external environment known as the epithelium. During development, the epithelium undergoes a series of morphogenetic events which alters the shape and size of epithelial cells, enabling them to perform tissue specific functions in mature tissue. During morphogenesis, cells sense the mechanical forces and establish polarity through cell proliferation and rearrangement according to morphogenetic signalling pathways. This manoeuvre is achieved by the underlying actin cytoskeleton network which enables cells to resist the tension and stresses of morphogenesis via alteration of filament dynamics and network architecture. In vivo, numerous actin-regulatory proteins generate various polymerized forms of straight, branched, or contractile actin-myosin filaments, regulating dynamic actin filament turnover. The robust actin cytoskeleton provides the cell with protrusive and contractile forces that enable cells to migrate, maintain, and change its shape and form during morphogenetic events. Actin filament depolymerization is accomplished by ADF/cofilin (Drosophila homolog twinstar) binding to actin monomers (G-actin) and actin filaments. However, ADF/cofilin alone is not very efficient in promoting disassembly of actin monomers, especially in subcellular regions where ADF/cofilin is highly concentrated. AIP1 (Drosophila homolog flare) then enhances actin depolymerization via preferential binding to ADF/Cofilin rich regions in vitro. The aim of my thesis was to study the localization and roles of AIP1 and cofilin in follicular epithelium during Drosophila oogenesis. My results showed that Actin-Interacting-Protein-1 (AIP1) was expressed throughout oogenesis. AIP1 expression was increased in cell type-specific manner and AIP1 showed spatiotemporal localization in follicular epithelium during oogenesis. Silencing of AIP1 led to accumulation of ectopic F-actin aggregates, localization of which may reflect the cellular sites of dynamic actin reorganization in the follicular epithelium. My results also indicate that AIP1 may be indirectly responsible for maintaining epithelial integrity as its silencing resulted in formation of epithelial gaps throughout follicular epithelium. Also delays in border cell migration were observed. Considering the above, understanding how AIP1 functions in Drosophila morphogenetic events would therefore pave the way for a greater understanding of how this protein works in other organisms. The knowledge gained may also be used to extend the current understanding of the role of actin binding proteins in diseased states.

The increased rates of population growth and urbanization worldwide raises the question of food security and self-reliance in cities. In view of this situation, in recent years there has been a re-emergence of urban agriculture in its traditional form and in new variations, such as on urban rooftops. A number of rooftop urban farms exist in the world; however, very few studies have been done to establish the quality of crops they produce, specifically concerning the concentrations of contaminants. The main purpose of this study was to investigate levels of contamination in edible plants grown on urban rooftops. I determined concentrations of polycyclic aromatic hydrocarbons (PAH) and trace metals in the biomass of three types of horticultural crops grown in the city of Helsinki, Finland. Lettuce, radish and peas were planted on five rooftops in various areas of Helsinki and control samples were acquired from local food stores and markets. Both groups of crops were analyzed for concentrations of 11 trace elements using the Elan 6000 ICP-MS and 16 PAHs using Shimadzu GC-MS-QP2010 Ultra system with the AOC-20i /AOC-20s autosampler. Additionally, lettuce and pea samples from the roofs were analyzed washed and unwashed to establish levels of particulate contamination on the surface of plants that can be mechanically removed through washing. Results obtained suggest that concentrations of PAHs and trace metals in rooftop vegetables in Helsinki are very low and the differences in their concentrations compared to control (store) samples are insignificant. This demonstrates that the consumption of vegetables produced in uncontaminated soil on urban roofs in Helsinki is safe. All samples showed concentrations well below the safety limits for heavy metals and PAHs established in the European Union (EC, 2006). Finally, there was a difference in concentration of PAHs and trace metals between washed and unwashed samples, however most of the results did not show statistical significance.

Social behaviour can be divided into neutral, positive, and negative, depending on the social context. Positive social behaviour involves affiliative prosocial interactions that encourage social and emotional cohesion. Rat (Rattus norvegicus) is a globally distributed common rodent species adapted to living near humans. Rats are intelligent and social animals with reciprocal prosocial behaviour. However, research on the social behaviour of rats is concentrated in laboratory settings and very little is known about the social behaviour of free-living rats. Rats arouse strong prejudice in humans and are considered aggressive. Despite a long history of coexistence, there are still strong conflicts between humans and rats. In this study, I used camera trap data to investigate the types of social behaviour in free-living rats and the time allocation of different behaviours. I investigated how the rats' behaviour is divided into socially neutral or positive and negative behaviour in relation to the total time spent on the behaviour. I also investigated the types of social behaviour that occur when rats approach each other and the frequencies of these different behavioural models. For the behavioural analyses, I used data-driven ethograms that I made and the behavioural analysis software BORIS. I found that the majority (over 96.2 %) of the social behaviour of the free-living rats in my study population was neutral or positive behaviour as measured by the duration of the behaviour categories. I also found that the most significant proportion of social behavioural models in rats was socially neutral or positive. Agonistic behavioural models were rare and occurred mostly between adults. In contrast, rats exhibited a moderate amount of prosocial behaviour, particularly in the form of food sharing and muzzle touching. My study brings new information to the limited previous research on the behaviour of free-living rats. The results suggest that most of the social behaviour in free-living rats would be neutral or positive behaviour, and agonistic behaviour in rats would be relatively rare. To the best of my knowledge, this work is the first study to analyse the social behaviour of free-living rats from camera trap data. Objective research data on the social behaviour of rats may mitigate prejudice against rats and attitudes towards rats may become more positive. This can mitigate conflict between humans and rats and promote peaceful coexistence. This work can be used as a pilot for future studies. The information this work provides can also be used, for example, to educate people about their attitudes towards rats.

Työn tavoitteena oli muodostaa kokonaiskuva sähköjärjestelmän sisäisistä ja ulkoisista vuorovaikutussuhteista. Sähköntuotantoa tarkasteltiin ympäristöönsä kytkeytyvänä systeeminä tieteidenvälisestä näkökulmasta. Tätä tarkoitusta varten rakennettiin menetelmä laajan kokonaisuuden hahmottamiseksi ja sovellettiin sitä sähköntuotannon alalle. Menetelmäperustuu grounded theoryyn ja systeemiajatteluun: Aineisto kerättiin ja luokiteltiin grounded theorya soveltaen. Systeemiajattelua käytettiin aineiston analyysissä ja aihealuetta kuvaavien mallien luomisessa. Aineisto kerättiin haastattelemalla sähköntuotannon ja -kulutuksen asiantuntijoita. Sen pohjalta rakennettiin useita alamalleja kuvaamaan sähköntuotantokompleksin osajärjestelmiä sekä näitä yhdistävä päämalli. Alamallien aihealueiksi muodostuivat tekninen sähköjärjestelmä, sähköjärjestelmän talous, sähkönsäästö, yhteiskunnallinen vaikuttaminen, ympäristö sekä tuotantorakenteen uusiminen. Lisäksi työssä esitettiin aineistosta nousseita kriteerejä hyvälle sähköjärjestelmälle ja sähköjärjestelmään liittyviä toimijoita. Mallien yhteydessä käsiteltiin myöseri tuotantomuotojen ominaisuuksia. Työn tuloksia tarkasteltiin kriittisesti kirjallisuuden valossa ja arvioitiin luotujen mallien sovellettavuutta. Malleja on mahdollista hyödyntää tieteenalarajoja ylittävän energiatutkimuksen jäsentäjänä sekä arvioitaessa kestävämmän energiapolitiikan edellytyksiä järjestelmätasolla.

Tiivistelmä–Referat–Abstract Background: Cancer is one of the leading causes of death around the world and in Finland. Ambitious research projects have been carried out for decades investigating cancer and how it spreads. Over 35 years ago, the systems that regulate vascular formation were discovered; the vascular endothelial growth factor (VEGF)-VEGF receptor VEGFR system and the more recent Angiopoietin-TIE system. These are the main endothelial growth factor receptor pathways involved in regulation of vessel quiescence and angiogenesis. The VEGF-VEGFR system is the first discovered endothelial cell (EC) specific receptor tyrosine kinase (RTK) signaling system. VEGF is a major growth factor involved in proangiogenic activity and vascular permeability when bound to its receptor, VEGFR2. Tumor cells take advantage of the VEGF-VEGFR2 system by secreting VEGF to stimulate angiogenesis in surrounding tissue to create new blood vessels allowing for greater access to nutrients and oxygen for tumor growth. The Angiopoietin-TIE system is the second EC specific RTK signaling system that was discovered. Angiopoietin-1 (ANG1) is the ligand for the TIE2 RTK. ANG1 is an obligatory TIE2 agonist and its effects on intracellular signaling, cell cytoskeleton, and junction-related molecules allows ANG1 to restrict the amount and size of gaps that are formed at EC junctions in inflamed vessels, increasing barrier function and decreasing vascular permeability. Angiopoietin-2 (ANG2) is an autocrine context-dependent TIE2 agonist/antagonist which is implicated in stimulating pathological angiogenesis, inflammation and vascular permeability. Integrins are important cell surface receptors that all cells use to communicate with their environment. Recently, it has been discovered that ANG2 is capable of inducing pathological angiogenesis, and can destabilize ECs when bound to integrin, specifically β1-integrin, via ANG2 N-terminal region. Objectives: The general aim of this study was to discover which part of angiopoiten-2’s N-terminus region was responsible for integrin activation. Materials and Methods: Fibronectin fragment containing type III 7-10 domains was produced and fluorescently labeled with Alexa 647. Integrin activation was measured using the fluorescently labeled Fibronectin III 7-10 and angiopoietins. Fluorescence activated cell sorting (FACS) was used to collect the results, which were analyzed using excel. Chimeric angiopoietins were produced using retroviral vectors and used for FACS experiments. A cell internalization assay was performed in Hela cells using CellTracker™ Orange CMRA and angiopoietin proteins, stained with secondary antibody anti-human Alexa 488 and Texas Red Phallodin. Results: Optimization of the FACS assay defined the minimum number of cells required to reliably measure integrin activation and showed that BD Accuri FACS machine was better suited than Guarva FACS machine for the assay and that the amount of integrin varied between cell passages used for the assay. In addition, it was essential to ensure a homogenous mix of cells and recombinant proteins during the assay and the quality of the produced FN III 7-10 was critical for the success of the assay. Results from the FACS assay confirmed that ANG2 is capable of activating integrin. In addition, chimeric angiopoietins that were expressed and secreted from CHO cells, were capable of activating integrins to a variable degree. The results confirmed the importance of ANG2 N-terminus in integrin activation. Cell internalization assay visually demonstrated angiopoietin binding to Hela cells. ANG2 was internalized by the cell and resistant to the acid wash, while the majority of ANG1 bound to the cell surface was washed away by acid wash. Conclusions: In this thesis work, integrin activation assays were optimized and carried out, along with cell internalization assays, to determine which specific part of ANG2 is responsible for inducing integrin activation. The findings from this work confirmed that ANG2 is capable of activating integrin. Several chimeric constructs were successfully expressed in CHO cells, and the cell supernatants were used to activate integrins. However, more studies are needed to determine which specific region of ANG2 is responsible for integrin activation. Investigating angiopoietin induced integrin activation would allow for a better understanding of the angiopoietin signaling pathway with potential translational significance.

Driven by the growing world population and increased food demand, the conversion of natural habitats into agricultural lands is occurring at an unprecedented rate. This is in turn the leading driver of the current biodiversity crisis, particularly in tropical forest areas characterised by prominent species diversity. Due to an accelerating cash-crop expansion, the once forest-savannah landscape of Northern Guinea-Bissau is now notably occupied by cashew orchards, in addition to scattered forest patches and floodable rice paddies. So far, it remains unknown how these kinds of human-modified landscapes can sustain mammal species over contrasting seasons, and how the habitat use varies across feeding guilds. To address this gap, this study aimed to understand how medium-sized mammals make use of mosaic-like landscapes in Northern Guinea-Bissau by considering the interactive effects of (1) habitat type: forest patch, cashew orchard and rice paddy and (2) season: before (June-July 2022) and after (October-November 2022) the peak of the rainy season. To do so, in each of the two seasons we conducted a 30-day consecutive camera-trap survey across seven landscapes, each of which comprised the three habitat types, amounting to 21 sampling sites. I evaluated mammal species richness, abundance (number of records) and composition across habitat types and seasons at the assemblage-level and discussed the species-specific habitat dependency. I further analysed species abundance across four feeding guilds: carnivores, insectivores, herbivores and omnivores. Based on a sampling effort of 1200 camera-trap days and 940 records, I identified 21 mammal species from 10 families and five orders. At the assemblage-level, species richness and abundance were similar between habitat types, but higher after the peak of the rainy season, except for rice paddies. Forest and cashew habitats shared similar species composition, which differed from rice paddies. Habitat-dependent species were found in each of the habitat types. At the feeding guild-level, in both seasonally periods carnivores and insectivores were less abundant in cashew orchards, while omnivores were more abundant. The results demonstrate that habitat conversion is likely to disrupt the functional structure of mammal assemblages. Maintaining heterogeneous landscapes, including both forested and open-area habitats, is crucial to maximize the integrity of mammal assemblages in Northern Guinea-Bissau. These findings can be used as baseline information in effective conservation measures in Guinea-Bissau and other tropical regions undergoing rapid conversion for cashew cultivation.

Climatic cycles lead to changes in habitat suitability, which in turn can lead to allopatry, i.e. isolation, between populations. Lack of gene flow between allopatric populations causes them to diverge through accumulation of genetic differences that can create incompatibilities between lineages upon secondary contact in the form of lowered survivability or reproduction rate in hybrids. Incompatible genes act as reproductive barriers and keep lineages isolated by selection against hybrids, while gene flow and recombination work as a counterforce to selection promoting admixture. Reproductive barriers like these are most often found inside hybrid zones and are well demonstrated in nature, but the isolating effect of individual genetic incompatibilities on genome-wide gene flow is still an open question. Here we test if selection counteracting gene flow maintains a narrow hybrid zone between two subspecies of the meadow grasshopper Pseudochorthippus parallelus. We targeted 0,01 % of the 13 GB genome, recovering a 29,1 mean coverage per locus per individual in targeted regions, when mapping against a transcriptome. We find that, for the nuclear markers, the hybrid zone is narrower than expected under a neutral scenario of no selection, suggesting that it is maintained by selection against hybrids. We also find significant isolation by distance, suggesting gene flow across the hybrid zone despite selection against hybrids. Different parts of the genome show significant excess or deficit of heterozygotes, suggesting that selection and gene flow are heterogeneous throughout the genome. Combined, our results show that reproductive isolation between recently diverged lineages can evolve quickly despite gene flow in neutral and positively selected sites.

Triple-negative breast cancer (TNBC) accounts for 10-15% of all breast cancer cases and has the worst clinical outcome. Characterizing features of TNBC are high recurrence and mortality rates, and the absence of three commonly targetable breast cancer biomarkers estrogen receptor, progesterone receptor, and HER2, limiting the number of targetable therapy options. Cytotoxic CD8 positive T cells play a crucial role in the anticancer immune response and act as a major component of successful cancer immunotherapies. However, cancer cells can evade T cell-mediated killing by overexpressing programmed death-ligand 1 (PD-L1) resulting in T cell exhaustion and limited immune response via the interaction with programmed death protein 1 (PD-1). Systemic anti-PD-L1/PD-1 therapies aim to prevent this immunosuppressive mechanism, but they are burdened with potentially life-threatening autoimmunity-type adverse effects. Therefore, cancer cell-specific targets to downregulate PD-L1 could offer efficacious and less harmful ways to overcome PD_L1/PD-1 mediated immunosuppression. Serine protease hepsin is commonly overexpressed in many solid tumors where it is responsible for the activation of HGF/MET signaling pathway as well as degradation of desmosomes and hemidesmosomes leading to the loss of epithelial integrity, invasion, and metastasis. Earlier studies have linked hyperactive HGF/MET pathway to the upregulation of immune checkpoint molecule PD-L1. In this thesis, I show how pharmacological inhibition of hepsin leads to decreased MET activity and downregulation of PD-L1 in a panel of TNBC cell lines. My results demonstrate the potential of hepsin-mediated regulation of PD-L1 in tumor immunosuppression, and hint at the potential of hepsin as a therapeutic avenue towards safe and efficacious immunotherapy in the future. These results are part of a larger study addressing the role of hepsin as a regulator of PD-L1 breast cancer.

Climate change is expected to increase the frequency and intensity of heatwaves in Finland. Heatwaves increase morbidity and mortality, especially among the elderly and chronically ill. Home care services are in an important role supporting the functioning ability and quality of life among populations vulnerable to heat. This study presents a qualitative empirical case study to understand heatwave adaptation in municipal home care services in Helsinki. The purpose of this study is to explore, describe and analyse the effects of the 2018 heatwave in the context of home care services, and the services’ capacity to adapt to heat. The data was collected by conducting semi-structured interviews with home care workers both on the operational and strategical levels. Theoretical frameworks regarding extreme heat vulnerability and local adaptive practices were used to support the analysis. The results suggest that heatwaves have caused challenges for both workers and customers. While the working ability of home care staff may be reduced due to thermal stress, the customers’ reduced functioning ability may simultaneously increase the need for care. Some workers had experienced fatigue, and customers were described having typical heat exhaustion symptoms. Workers adaptive practices were mostly reactive responses aimed at reducing the vulnerability of customers to heat. Interviewees described having taken preventive measures to limit customers’ exposure to heat and prevent adverse heat-related health outcomes by monitoring customers’ hydration more carefully. No long-term preparedness measures were identified on the strategical level. The city had supported workers by offering mineral drink bottles and providing instructions for coping in hot weather. In conclusion, workers have an active role in adaptation, but it might be limited by their own thermal stress, customers’ different health conditions and resources, as well as service-level stressors such as lack of staff. Because heatwaves are expected to increase in the future, home care services’ preparedness to heatwaves might need to be improved. It would be important to consider adaptation needs of both workers and customers as they can be interrelated in the sense, that care is dependent on workers ability to function. In a wider societal framework, the adaptive capacity of home care should be secured through providing sufficient resources for these services. The latter is even more important in the light of future trends regarding the aging of population, increase in need for home-based services and decrease in workforce availability. More research is required on the effects of heatwaves on the most vulnerable populations, what adaptation needs there might be as well as how this relates to service provision.