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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.

Pluripotent stem cells (PSC) can exists in both primed and naïve states. The conventionally derived human PSCs represent the later primed state of pluripotency during embryo development, while the naïve state resembles the inner cell mass (ICM) of pre-implantation blastocyst. Primed human PSCs can be reverted chemically by transient histone deacetylase (HDAC) inhibition back to the naïve state in vitro. The reverted PSCs can then be characterized based on their morphology and expression of selected naïve markers using immunocytochemistry and RT-qPCR assays. Leucine twenty homeobox (LEUTX) is one of the genes expressed during the early stages of embryo development and is capable of activating the transcription of multiple genes, including pluripotency-associated genes, which are upregulated during the human embryonic genome activation (EGA). LEUTX expression could potentially improve the naïve reversion efficiency or the maintenance of naïve PSCs by driving the transcriptome of primed PSCs back towards the earlier cell stages of embryo development, potentially even to cell stages that precede the naïve state. The aim of this thesis was to setup the naïve reversion protocol and study the effects of LEUTX on the reversion by using the generated and tested H9 activator cell line for targeted activation of endogenous LEUTX expression. First, a conditionally stabilized CRISPRa activator cell line was generated for targeted activation of endogenous gene expression in H9 cells. Then sequence-specific guide RNAs (gRNA) targeting LEUTX for activation were introduced to the activator cell line. Using the generated activator cell line during the naïve reversions allows the targeted activation of specific genes, here LEUTX, and thus enables studying the effects of these genes on PSCs during the naïve reversion protocol. The induced activator cells expressing LEUTX managed to form four times as many naïve resembling colonies during the reversion compared to the controls, but most of these were lost after changing the medium conditions towards the end of the protocol. After the reversion was complete, the reverted PSCs were characterized as naïve PSCs based on their domed morphology and the high expression of naïve markers NANOG, KLF17, TFCP2L1 and DNMT3L when compared to the primed PSCs. The naïve reversion protocol was set up and optimized successfully and can now be used as a reliable way of obtaining human naïve PSCs for further experiments studying and modelling the earlier developmental stages during embryo development. Furthermore, the generated H9 activator cell line worked as intended and can be utilized for studying the effects of other targeted genes during the reversion or in the reverted naïve PSCs.

Binge eating disorder (BED) is a common eating disorder that includes eating a large amount of food in a short period of time and is often associated with obesity. Patients can suffer from stress, anxiety, and metabolic syndrome caused by the weight gain, but no effective medication for both psychological and physiological issues have been discovered. This thesis studies the potential of short-chain fatty acids (SCFA) in reducing binge-like eating behaviour in a mouse model that does not include food restriction. The model includes a 24 h bingeing period with high-fat food once a week. SCFA butyrate, propionate, and acetate were administered to mice via 1 g/kg i.p. injections or 200 mM drinking water for three days, and their effects on energy intake during the bingeing period were measured. The results show that SCFA can significantly reduce binge-like eating behaviour in mice in the short term, but long-term effects vary. I.p. butyrate, propionate, and acetate decreased energy intake by 68%, 57%, and 62% during the first hour, respectively. SCFA via drinking water did not decrease energy intake a lot, and the results were inconsistent between animals. These results suggest a potential for SCFA to attenuate bingeing episodes when administered acutely, but the mechanisms remain to be discovered.

Eliölajit ovat jatkuvassa vuorovaikutuksessa niin fysikaalisen ympäristönsä, kuin muiden eliölajienkin kanssa. Nämä vuorovaikutukset voivat olla osapuolille negatiivisia, neutraaleja tai positiivisia. Fasilitaatio tarkoittaa sitä, että joku laji edesauttaa toisen lajin selviytymistä. Äärimmäinen esimerkki fasilitaatiosta on perustajalaji. Perustajalaji on laji, joka pelkällä läsnäolollaan tarjoaa muille eliöille kriittisiä resursseja, joita ilman muut lajit eivät voi selviytyä. Nämä resurssit voivat olla esimerkiksi ravintoa, suojaa tai elintilaa. Alustaansa kiinnittyvät simpukat ovat perustajalajeja, joita tavataan kaikilta maailman merialueilta. Esiintyessään tiheinä kasvustoina kalliorannoilla ne tarjoavat lukuisille selkärangattomille eläimille suojaa aallokon voimalta ja pedoilta, ravintoa ja elintilaa lisääntyneen sedimentaation myötä, sekä runsaasti sekundaarista kiinnittymispintaa. Alustaansa kiinnittyvät simpukat muodostavat perustan habitaatille, joka lopulta muotoutuu simpukoiden ja muiden lajien yhteisvaikutuksella. Vähäsuolaisessa ja -lajisessa Itämeressä sinisimpukka (Mytilus trossulus x edulis) on alustaansa kiinnittyvänä simpukkana erittäin tärkeässä roolissa. Sinisimpukkaa esiintyy pinnan läheltä aina kymmenien metrien syvyyteen asti, kunhan kiinnittymiseen sopivaa alustaa vain on tarjolla. Simpukoiden esiintymiseen Itämeressä vaikuttavat monet tekijät, joista tärkeimpinä ovat aallokko joka aiheuttaa fysikaalista stressiä, ja alhainen, itää ja pohjoista kohti pienentyvä suolapitoisuus joka aiheuttaa fysiologista stressiä. Paikoin erittäin runsaina esiintyvät sinisimpukat edesauttavat sedimentin kertymistä muodostamansa kolmiulotteisen matriisin onkaloihin mikä mahdollistaa myös pehmeän pohjan lajien esiintymisen kalliorannoilla. Sinisimpukkayhteisössä onkin piirteitä sekä pehmeistä, että kovista pohjista, mikä tekee niistä edullisia elinympäristöjä runsaalle määrälle erilaisia selkärangattomia eläimiä. Tässä tutkimuksessa tutkittiin sisäsaaristosta ulkosaaristoon voimistuvan aallokon vaikutusta sinisimpukka-rakkohauru -yhteisön rakenteeseen kolmella lähellä toisiaan sijaitsevilla merialueilla läntisellä Suomenlahdella, missä suolapitoisuus laskee läntisimmän ja itäisimmän tutkimusalueen välillä ainoastaan muutamilla promillen kymmenyksillä. Näytteitä noudettiin sukeltamalla 36:sta eri pisteestä kolmen metrin syvyydeltä rakkohauruvyöhykkeeltä, neljältä eri avoimuusvyöhykkeeltä. Näytteistä havaitut eläintaksonit tunnistettiin ja eläinten yksilömäärät laskettiin, ja sinisimpukoiden sekä rakkohaurun (Fucus vesiculosus) kuivapaino määritettiin. Tilastollisilla menetelmillä selvitettiin eliöyhteisön rakenteen eroja näillä kolmella alueella, sekä kasvavan avoimuuden vaikutusta. Lisäksi selvitettiin korreloivatko tavattujen eläinlajien yksilömäärät sinisimpukan tai rakkohaurun biomassan kanssa. Sinisimpukka oli kaikilla näytepisteillä runsain tavattu laji, ja jäljessä yksilömääristä puhuttaessa sinisimpukkayksilöitä ei huomioida. Alueet eivät eronneet toisistaan taksonien tai eläinyksilöiden kokonaismäärien osalta, mutta yksittäisillä taksoneilla eroja kuitenkin havaittiin. Avoimuudella havaittiin olevan merkittävä vaikutus eliöyhteisön rakenteeseen. Avoimuuden kasvaessa havaittujen taksonien määrä laski ja runsaimmat taksonit vaihtuivat sedimenttiä suosivista nilviäisistä vapaasti uiviin äyriäisiin, sen sijaan eläinten kokonaisyksilömäärissä merkitseviä eroja ei havaittu. Merkittävä osuus tavatuista yksittäisistä taksoneista korreloi negatiivisesti kasvavan avoimuuden kanssa, avoimuuden kanssa positiivisesti korreloivia taksoneita oli vähemmän. Sinisimpukoiden biomassan kanssa havaittiin korrelaatiota usealla taksonilla, kaikki positiivisia, sen sijaan rakkohaurun biomassan kanssa korrelaatiota havaittiin ainoastaan yhdellä taksonilla. Tämä tutkimus osoittaa, että avoimuudella on selkeä vaikutus perustajalajina toimivan sinisimpukan ympärille muotoutuneeseen eliöyhteisöön ja sen rakenteeseen. Suolapitoisuuden vähäinen lasku tutkimusalueiden välillä sen sijaan ei vielä merkitsevästi vaikuta sinisimpukkayhteisön rakenteeseen, vaikka yksittäisillä lajeilla - merkittävimpänä juuri sinisimpukka - viitteitä vaikutuksista havaittiinkin. Sinisimpukan merkitys muuhun lajistoon on merkittävä, rakkohaurun merkitys on sen sijaan varsin vähäinen.

The spreading of non-indigenous species by human activities is a growing problem globally. Invasive species are generally assumed to have negative impacts on ecosystems, because they threaten biodiversity and the balance of ecological systems. Other simultaneous changes in the ecosystem can impact, or intensify the effects of, the invasion. The invasive rock shrimp Palaemon elegans, is an invasive species that has spread to the Baltic sea via human introduction in the early 2000's. There have also been drastic changes in the ecology of Baltic sea, particularly the increase of primary production. A common mesopredator, the three-spined stickleback Gasterosteus aculeatus, has greatly increased in number in the Baltic sea in recent years. It is presumed to influence the primary production by predation of zooplankton grazers. P. elegans is an omnivore that both grazes filamentous green algae, as well as preys upon the invertebrate grazers that live amongst the algae. If the invasion of P. elegans influences the populations of stickleback, it might also influence the accumulation of primary production. Recent studies have shown, that P. elegans can potentially influence the reproductive behavior of stickleback, but the effect on the success of reproduction has not been proven. This study was composed of two parts: field monitoring and a mesocosm experiment. In the monitoring, individuals of stickleback and P. elegans were caught, counted and measured in three shallow bays and two depths from May to August of 2015. The differences in number of caught individuals were analyzed using Kruskal-Wallis analysis of variance and differences in lengths were analyzed with Mann-Whitney U-test. The effect of P. elegans on sticklebacks was analyzed using covariance analysis. The hypothesis was, that the amount of P. elegans and stickleback or their lengths would show negative correlation, which could be a sign of interaction through predation or resource competition. In the mesocosm experiment stickleback fry were exposed to P. elegans or a non-parent stickleback in tanks with filamentous algae Cladophora glomerata and associated fauna. The resulting differences in in fry number, fry size and the amount of algae between treatments in the tanks were analyzed with Kruskal-Wallis analysis of variance. Correlations between variables were analyzed using Spearman's rank-order correlation. The hypothesis was that P. elegans would have a negative effect on the amount of fry through predation, or the size of the fry through perceived predation risk. In the field study, no significant correlations were found between P. elegans and sticklebacks, and therefore the results do not suggest a causal link between the two species. Differences between the areas were found, which were attributed to physical differences between the areas. In the mesocosm experiment not enough repetitions were accumulated to provide reliable results. The increase of P. elegans in the Baltic sea is most likely not going to affect the three-spined stickleback via direct predation. P. elegans appears in the shallow bays where sticklebacks reproduce later in the year and it consumes mainly algae and invertebrates. Even though P. elegans will feed on fish eggs if there is an opportunity, stickleback males defend their nests fiercely. The invasion of P. elegans in the Baltic sea is very recent, but it can affect the accumulation of filamentous algae due to their great number. It feeds on invertebrates, but can itself be a potential food item in the diet of ie. cod.

With growing fragmentation of elephant habitats across the world, elephants are coming in closer contact with humans, leading to increasing human-elephant conflict over limited space and resources. Laikipia county in Kenya represents one such region where conflict with elephants has been (and continues to be) a widespread problem, stemming from intense land-use zoning since the 1970s. This conflict mainly takes the form of crop raiding by elephants in community farmlands adjoining conservation areas. Electric fencing has been the widely used conflict management tool in the region to prevent elephants from entering croplands. However, the establishment of electric fences can often have hidden political underpinnings, both caused by and resulting in conflicting interests of different land users. As human-elephant conflict is multidimensional, it is essential to incorporate both human and wildlife dimensions when assessing the effectiveness of electric fences in conflict mitigation. While there is a growing body of research on the ecological effects of electric fences, the role of social perceptions in long-term fence effectiveness is often neglected. In this study, I therefore conducted a combined social and ecological assessment of electric fences in Laikipia. For this, I evaluated the perceptions of three local communities (Mutara, Ex Erok and Lorien) towards two major electric fences in Laikipia: the West Laikipia Fence and the Lorien Community Fence. I conducted 188 individual interviews with farmers (and opportunistically pastoralists) in all three communities, comprising questions on demographics, human-elephant conflict, electric fences, and involvement of communities in fence management. I then combined this information with data on fence breaking and crop raiding behaviour of elephants to effectively inform electric fence management strategies in the region. First, I looked at changes in the perceptions of Mutara and Ex Erok between 2016-2022, following upgrades made to the West Laikipia Fence after 2016, through a comparison of results with previous research. Second, I investigated potential factors influencing community perceptions towards fence effectiveness. Third, I mapped fence break and crop raiding hotspots in the three communities. And fourth, I determined the environmental factors affecting crop raiding intensity. Both Mutara and Ex Erok showed more positive perceptions towards fence effectiveness in 2022 as compared to 2016. The main factor found to influence fence perceptions was community involvement in fence management. Communities involved in fence management had more positive fence perceptions than those with no involvement. Crop raiding hotspot mapping revealed that some areas within each community were more affected by crop raiding than others. Fence break hotspot mapping identified fence sections of the West Laikipia Fence more prone to breakages by elephants. Finally, crop raiding intensity in a given farm was found to be strongly affected by the diversity of crops grown there, and weakly by its distance from the nearest roads and electric fences. My results therefore contribute to a better understanding of patterns of crop raiding and fence breakages of elephants in Laikipia. My findings highlight the importance of including sociological data from local communities in assessments of electric fence effectiveness, and also provide empirical evidence on the importance of involving local communities in electric fence management. The findings from this study can serve as a reference to relevant stakeholders for future improvements in electric fence management in Laikipia and elsewhere.

The concept of sustainability has been discussed a lot in academic and political contexts. While especially the ecological dimension of sustainability has been widely focused on due to various environmental crises, the social dimension has been less studied. In this thesis, I analyse social sustainability through political discourses in the Finnish context. Finland has received good results in the field of social policy and throughout its history, central labour market organisations have had an institutional role in the development of social policies. This thesis analyses how Finnish central labour market organisations discuss social sustainability when they set their objectives for the 2019-2023 government term. Adopting a critical approach, I study the role and representation of social sustainability in the objective documents. My two-part research 1) constructs a definition for social sustainability based on literature, and 2) analyses the empirical data and discourses found within. The findings of this thesis present a five-part definition for social sustainability and four key discursive themes which emerge from the empirical data. The results from empirical data show that in the objective documents social sustainability is for example discussed in a bureaucratic way, sometimes seen as an instrument benefitting the society. The research also underlines the difficulty of defining and analysing the vague concept of social sustainability and discusses how and why social sustainability could be researched in the future.

Chitinolytic enzymes belong to a group of pathogenesis-related proteins, which are induced in plants by a pathogenic attack. They have also been shown to function in abiotic stresses and related to signalling. Chitinases catalyze the degradation of β-1,4-N-acetyl glucosamine units of chitin. Chitin is not found in plants, but for example the shells of invertebrates, cell walls of certain fungi, algae and bacteria contain it abundantly. Lately chitinases have gathered attention because of their potential utilization possibilities in medicine, agriculture, food industry and biofuels. Strong chitinase gene expression and also chitinolytic activity has been found in a spruce (Picea abies L. Karst.) cell culture, which produces apoplastic lignin into the medium. Plant chitinases are known to be induced also in developmental processes. Chitinase-like genes have been shown to be essential in cellulose synthesis and in development of cell walls and tracheary elements and also affected the localisation of lignin in tissues. Therefore, the secretion of chitinases into the culture medium has not necessarily been caused by stress and chitinases might use also some endogenic substrate in addition to chitin. Because chitin is a structural component of plant pathogens but not present in plants and the growing circumstances of the studied aceptic spruce cell culture were stable, the research hypothesis was, that the secreted chitinases in the culture medium were not a stress reaction but related to development and besides chitin of the pathogens they utilize some own polysaccharide substrate of spruce. Additional hypothesis was connection of the strong expression of chitinases and chitinase-like genes in the culture medium and the production of apoplastic lignin by the spruce cell line. The aim of the study was to characterize the chitinases and chitinase-like enzymes of the spruce cell suspension culture medium and developing xylem by isolating, purifying and cloning them and by producing them heterologously. The aim was also to identify the putative endogenous substrates for the chitinases and chitinase-like proteins to reach better understanding about the meaning of the chitinases in the development of the spruce tissues. Two chitinases of the spruce cell suspension culture were isolated and purified by chromatographic methods. One chitinase gene in spruce cell culture and one chitinase-like gene in spruce xylem were cloned, after which the chitinases and chitinase-like proteins were produced in Pichia pastoris yeast. The total proteins of the culture medium, the purified chitinases isolated from the medium and the chitinases and chitinase-like proteins produced in P. pastoris were used to examine their substrate alternatives with the carbohydrate microarray method. The connection between apoplastic lignin and the chitinolytic enzymes in culture medium was not found and obvious candidates for the endogenous substrates were not detected. However, the mannan degradation in the presence of the chitinases was strong enough to give reason to further analyses.

The thesis explores possibilities for mental health promotion in urban planning trough a case study of the community space in Lapinlahti, Helsinki. Lapinlahti is a former psychiatric hospital, and the area has in the 2010’s been developed through community efforts into a center for mental wellbeing and culture in Helsinki, a “Lapinlahti for all”. The future use of the area has been contested for the past years, with the City of Helsinki and the organizations at Lapinlahti having different views on how the area and it’s cultural and historical mental health legacy should be preserved and developed. In the discussions, statements and visions, the area’s mental health value has also been translated into urban planning, taking many forms. Mental health is a value that has traditionally not been prioritized or regarded as a value of its own in urban planning, and although the relationship between urban form and wellbeing is well known, urban (mental) health is seldom tied to cities physical- and land-use planning (Kim et al, 2022; Corburn 2004). The thesis approaches this topic by analyzing mental health as a planning objective, discussing how different understandings and approaches to mental health have affected the planning visions surrounding Lapinlahti. The thesis uses a theoretical framework of urban governance and critical discourse analysis (CDA) to seek an understanding to the different approaches to the area’s development, and identify the different understandings, connections and visions that surround Lapinlahti. The study identifies three discursive constructions of Lapinlahti: Lapinlahti as a site for cultural heritage, Lapinlahti as a place for mental health, and Lapinlahti as a site for development. The results show that all actors in their development schemes have considered the area’s mental health value from a cultural-historical perspective, viewing the area as a site for mental health history. This history is however understood and manifested in different ways for the actors, influencing different visions for how the area should be developed and what interests and/or values that should guide the development. The thesis continues with presenting three approaches for mental health promotion in urban planning, concluding that planning should be attentive of how the space is governed, the relationship between mental health and the space, and the activities and meanings embedded in space.