Recent Submissions

  • Hannus, Sinikka (Helsingin yliopisto, 2018)
    Developmental language disorders in children are common and constitute a common reason for support in both health care and school system. Specific language impairment (SLI) is diagnosed in Finland in accordance with the ICD (International Classification of Diseases) with either F80.1 or F80.2 diagnoses. The terminology related to SLI is not internationally unambiguous. Studies indicate that SLI may entail more extensive difficulties than those related purely to language and, also, that SLI in childhood persists into adulthood. SLI has been studied very little within the Finnish service system. The present study explored SLI in the primary health care of one Finnish town. The children participating in the study belonged to the multidisciplinary SLI in Vantaa study group. SLI in Vantaa consisted of all the Finnish speaking children born in 1998 and 1999 who had been diagnosed with the diagnosis F80.1 or F80.2 in the secondary health care, and their matched controls. The first data set assessed the test use of the speech and language therapists (SLTs). In the second data set, the test performance of the children diagnosed with SLI was compared to that of their matched controls. The third study analysed the prevalence of the diagnosed SLI in the SLTs’ statistics over a period of eleven years. The fourth study compared the home activities of the children with SLI with those of their matched controls. The tests that were considered to be the best in separating the children with SLI from their peers were the same ones that the SLTs had most confidence in and that they most frequently used. On the other hand, the SLTs used some tests to assess also other constructs of language than those for which these tests were originally devised. The prevalence of SLI remained lower than the internationally reported level, even though it did increase during the study period. The low prevalence raised the possibility of under-diagnosing of SLI. When comparing the peer groups in home activities, similarities outnumbered differences. The existing differences seemed to be related to something else than language difficulties. Unifying and developing the assessment procedures of SLI is needed in Finland. Organising the future studies in collaboration between the researchers and the clinicians may benefit the children with language disorders in the best possible way.
  • Wang, Cui (Helsingin yliopisto, 2018)
    Pleistocene glaciations have profoundly influenced the genetic diversity of organsims in the Northern Hemisphere. Large ice sheets covered vast areas of the Eurasian continent, driving species southward to different isolated refugia, often resulting in deep divergences within species. Phylogeographic studies carried out on Pungitius species based on mitochondrial DNA (mtDNA) support profound intraspecific genetic divergence in refugia during glaciation cycles. However, compared to species distributed at lower latitudes, those distributed at higher latitudes may have also occurred in cryptic refugia in periglacial areas during glaciations, complicating the inferences of the phylogeographic patterns of the fish species with a circumpolar distribution, such as the Pungitius sticklebacks. Moreover, comprehensive phylogenetic studies of Pungitius species have been lacking in the sense that not all extant species have been included into analyses. In this dissertation, I carried out phylogeographic studies on seven Pungitius species using both mtDNA and genome-wide nuclear SNP markers, with worldwide sampling of populations to shed light on intra- and interspecific divergence in this genus, as well as to study their historical demography and interspecific hybridization. By sequencing five mtDNA regions, I found six highly divergent Pungitius lineages including those corresponding to P. pungitius, P. platygaster, P. tymensis and P. kaibarae, and two independent monophyletic lineages of P. laevis. I also found a third lineage of P. laevis that clustered together with P. pungitius. To understand whether this clustering of the P. laevis lineage III and P. pungitius mtDNA was a result of convergence or interspecific introgression, I conducted phylogeographic and population genetic analyses using both mtDNA and nuclear gene sequences. The results indicated asymmetric mitochondrial introgression from P. pungitius to P. laevis and genetic admixture of these species. Hence, the results suggest that the P. laevis lineage III has experienced historical hybridization. Deep intraspecific mitochondrial divergence was found within P. laevis in central and southern France, coinciding with major drainages, suggesting that these areas correspond to distinct glacial refugia for the species explaining the observed intraspecific divergence. To further clarify evolutionary relationships between different Pungitius species and populations, as well as to study the prevalence and extent of introgression among recognized species, phylogenomic datasets were constructed from restriction-site associated DNA in combination with mitochondrial genomes. All divergences in the Western Palearctic were estimated to have occurred during the Pleistocene (≤ 2.6 Ma). The phylogenetic patterns suggest a major split in Pungitius genus occurred early in history, resulting in an East Asian group (P. kaibarae, P. tymensis, P. sinensis) and European - North America group (P. hellenicus, P. platygaster, P. laevis and P. pungitius). The genus probably originated from the Western Pacific and spread to Europe and North America through the Arctic Ocean in several waves after the opening of the Bering Strait. Four cases of incongruence between nuclear and mtDNA-based trees revealed evidence for frequent hybridizations and mitogenome capture during the evolutionary history of this genus. Further analyses of these four cases of cytonuclear incongruence also revealed evidence for nuclear introgression, but the estimated levels of autosomal introgression were low.
  • Forsgård, Richard (Helsingin yliopisto, 2018)
    Intestinal permeability is a key measure of gastrointestinal function and studies have associated increased intestinal permeability with several different pathologies. Clinically, increased intestinal permeability could contribute to disease pathophysiology by allowing unwanted substances to enter circulation and stimulate inflammatory processes. Thus, a better understanding of the factors and mechanisms that affect intestinal permeability could offer new insights on how to manage these diseases and disorders. The aim of this thesis was to investigate intestinal permeability changes under three separate settings. Chemotherapy-induced gastrointestinal toxicity is a major complication of cancer treatment and we examined if measuring intestinal permeability to iohexol could be used to assess the severity of this complication. We also hypothesized that chemotherapeutics affect the composition of intestinal microbiota and the global metabolome and studied how these alterations relate to increased intestinal permeability. In another study setting, we investigated whether intestinal permeability changes explain individual’s susceptibility to gastrointestinal symptoms during exercise. Finally, we treated intestinal tissue segments with a deoxycholic acid (DCA) concentration associated with high-fat feeding and examined the mechanisms by which it affects macromolecular permeability. Our results show that commonly used chemotherapeutics, running at a challenging pace for 90 min, and DCA concentration associated with high-fat feeding increase intestinal permeability. The observed increase in intestinal permeability after chemotherapy also correlated with the severity of gastrointestinal toxicity. Chemotherapy-induced gastrointestinal toxicity was also associated with unfavorable changes in the composition of intestinal microbiota which may play a role in the pathophysiology of intestinal complications during chemotherapy. Running-induced increase in intestinal permeability seems to result from intestinal ischemia but it did not explain the occurrence of gastrointestinal symptoms during the running test. The DCA-induced increase in macromolecular permeability appears to stem from direct interaction with the mucosa. However, we also observed evidence that DCA affects the intestine via a neural mechanism. Overall, these results demonstrate how different stressors can impair intestinal barrier function and possibly lead to various symptoms and complications.
  • Pajunen, Virpi (Helsingin yliopisto, 2018)
    The ongoing climate change and increasing anthropogenic pressure threaten the biodiversity on Earth. Elevated temperatures, changes in precipitation and intensive land use alter ecosystems and such changes are prone to escalate in the northern regions, especially in freshwater ecosystems. Information about the effects of climate on the distributional patterns of diverse aquatic micro-organisms has yet largely been lacking. This is a drawback as microbial species in freshwaters play crucial roles in ecosystem functioning as well as in environmental monitoring. Thus, it is necessary to disentangle the main drivers of microbial species distributions in order to predict the responses of freshwater communities to future environmental change and to ensure the accurate determination of the ecological status of ecosystems. This doctoral thesis aims to investigate the relative roles of climate, catchment properties and local environmental factors in the occurrence of the important freshwater micro-organisms both at species and community levels. This study, conducted at a regional scale (c. 1000 km), concentrates on unicellular stream diatoms, which are widely used in biomonitoring. The results showed that climatic factors are important drivers of stream diatom distributions and their influence may even outcompete the effects of local environmental variables. However, the relative importance of the factors governing diatom distributions varied along the anthropogenic land use gradient and among species. Climate was the main driver of species distributions in pristine environments, whereas local environment was more important in human impacted streams. Diatom assemblages were also found to be reliable predictors of both climatic and local environmental factors indicating their robustness as environmental proxies and bioindicators. This thesis contributes to the spatial research of aquatic micro-organisms as it brings a novel evidence of the biogeographical patterns of microbial species. This study revealed that climate, one of the fundamental drivers of species distributions on Earth, governs also the occurrences and abundances of stream diatoms even at regional scales. However, it is important to acknowledge that the effects of the most essential factors influencing diatom species may be context dependent and vary along the anthropogenic land use gradient. The ongoing climatic and subsequent environmental change may further complicate the species responses towards environmental factors. From an applied perspective, this study confirmed the reliability of stream diatom assemblages as bioindicators. However, diatom responses towards novel environmental conditions need to be reevaluated to assure their accuracy also in the future.
  • Olascoaga, Beñat (2018)
    Photosynthesis requires a balance between its light-dependent and light-independent reactions so that the energy input through photochemistry matches its consumption. Biochemical and physiological processes help to achieve this balance, as certain processes regulate the activity of light-dependent photochemical reactions, whilst others regulate the activity of temperature-dependent biochemical reactions. Biochemical and physiological processes also modulate the absorbed energy available for photosynthesis by diverting a fraction into non-photochemical pathways that dissipate energy as heat and fluorescence. Interestingly, certain biochemical and physiological processes behind the dynamics of photosynthesis correlate with leaf optical properties (LOPs), which represent an approach to characterising the dynamics of photosynthesis. Yet, how solid is our knowledge concerning the biochemical and physiological processes influencing LOPs, and how accurately do LOPs and the biochemical and physiological processes behind photosynthetic dynamics correlate when investigated across various spatio-temporal scales? This thesis investigated whether reflectance-based and fluorescence-based LOPs adequately correlate with the biochemical and physiological processes behind photosynthetic dynamics, and whether their correlations hold true at various spatio-temporal scales. This thesis demonstrates the validity of reflectance-based and fluorescence-based LOPs as optical proxies for investigating the dynamics of photosynthesis. However, it also identifies sources of variability that cause the correlations between photosynthesis and LOPs to break down. This thesis classifies the sources of variability in terms of methodological (i.e. over-simplification and technical/instrumental constraints) and spatiotemporal limitations. The over-simplification of processes behind the dynamics of photosynthesis and LOPs was addressed by studying the absorption of photosynthetically active radiation (PAR) by conifer needles. PAR absorption is generally considered to be chlorophyll concentration-dependent, yet this thesis shows it to be additionally modulated by the effect that waxes have on needle PAR reflectance. Due to the difficulties of directly measuring needle PAR absorption, PAR reflectance was used as a proxy of PAR absorption. To solve this technical/instrumental constraint, this thesis presents a new methodology that facilitates the direct estimation of PAR absorption. This thesis also demonstrates that certain LOPs appear to be insensitive to detecting the dynamics of certain biochemical and physiological processes over time. This was true for the photochemical reflectance index (PRI), which failed to detect zeaxanthin independent processes behind the thermal dissipation of the absorbed PAR. Lastly, this thesis shows that LOPs can also be influenced by leaf morphology, which could affect the optically-based monitoring of larger-than-leaf scales. Despite the caveats highlighted in this thesis, the potential to monitor the dynamics of photosynthetic activity by optical means is unquestionable, and the results presented here can contribute to reducing uncertainty in the characterisation of photosynthesis by optical means at varying spatio-temporal scales.
  • Jouhi, Lauri (Helsingin yliopisto, 2018)
    Head and neck cancers constitute the seventh most common cancer group worldwide. Their incidence has been declining in the Western world, along with the decrease in tobacco smoking. The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising over the last two to three decades in many Western countries. This trend is attributed to human papillomavirus (HPV), which is responsible for the majority of OPSCC cases, whereas, the incidence of HPV-unrelated OPSCC has decreased. HPV-positive OPSCC differs from the HPV-negative form in various aspects: Patients are younger, and they typically have less tobacco and alcohol consumption. They tend to have smaller primary tumors but more advanced disease in the neck. Patients with HPV-positive tumors have better odds of survival, but their post-treatment lifetime may be harmed by major treatment-related morbidity. Many prospective randomized trials delivering de-intensified treatment for this OPSCC patient group are currently ongoing. Validated predictive biomarkers could aid in the treatment individualization of OPSCC. The only well-validated prognostic biomarkers in OPSCC are HPV and protein p16, reflecting HPV involvement. Toll-like receptors (TLRs) are receptors, which initiate immunological cascades. In HPV-associated cervical carcinoma, alteration in the expression of TLRs has been observed. These receptors are also expressed in an altered pattern when HPV infection persists in the cervix. Therefore, these receptors could have a role in HPV-associated OPSCC. The first part of the present study analyzed the treatment and outcome in two patient series treated over a ten-year period. Study I included all OPSCC patients treated at the Finnish university hospitals, and Study II focused on the management of the neck in cN+ disease of patients treated at the Helsinki University Hospital. The cohort included 674 patients, and during the study period, the incidence of this disease increased, which mainly occurred in the group of patients carrying a HPV-associated tumor. The outcome of lateral-wall OPSCC (tonsil) remained similar compared to an earlier Finnish nationwide report, but the outcome of anterior-wall disease (base of tongue) slightly improved. Study II revealed that the relative rate of neck dissections had decreased while the delivery of definitive oncological treatment had increased. However, the regional control rate had not worsened. Regional failures occurred in patients with class cN2b or higher and they often developed on the contralateral side of the neck, including in patients with an ipsilateral primary tumor. The second part of this thesis study (Studies III and IV) evaluated the role of TLRs in OPSCC. As a pilot study, we analyzed TLR 2, 3, 4, 5, 7, and 9 expression, p16 expression, and HPV status in 35 OPSCC samples. TLR 5, 7, and 9 expression varied according to p16 and HPV status. Based on these results, we evaluated the association of TLR 5, 7, and 9 with clinicopathological and outcome data in a cohort of 202 OPSCC patients. The findings indicated that high TLR 5 expression and low TLR 7 expression were related to poor disease-specific survival in the group of HPV-positive OPSCC patients.
  • Malmi, Hanna (Helsingin yliopisto, 2018)
    The incidence and complications of peptic ulcer disease (PUD) have declined during the last decades in Western countries. The Helicobacter pylori (H.pylori) infection and the use of non-steroidal anti-inflammatory drugs are the two main risk factors for peptic ulcer disease. Despite the use of H.pylori eradication therapy and gastroprotective agents, mortality associated with PUD has not decreased as assumed. The aims of this thesis were to evaluate time trends in the incidence of PUD and its complications in hospitalised patients, their short- and long-term mortality, risk factors for mortality. Moreover, the prevalence of PUD among patients suffering from acute gastrointestinal bleeding (GIB) symptoms in the beginning of the 21st century in the capital area of Finland was studied. In the retrospective epidemiological cohort study, data on adult patients hospitalised and diagnosed with PUD was collected from the Hospital District of Helsinki and Uusimaa patient register during 2000-2008. The data was linked with Prescription Register of the Finnish Social Insurance Institution allowed detailed individual medicine purchase data and all patients were followed in the National Cause of Death Register until the end of 2009. In the prospective observational cohort study, data on hospitalised patients referred for acute upper endoscopy during 2012-2014 in Meilahti and Jorvi hospitals were collected. The incidence of peptic ulcers decreased significantly from 121/100000 in 2000-2002 to 79/100000 in 2006-2008. The rate of severe complications was also reduced, mainly due to a reduction in bleedings. The one-year cumulative incidence of recurrent peptic ulcers was 13%. The use of several drugs indicating comorbidity was associated with an increased risk for recurrence. No change in standardized mortality ratio was seen; 3.7% of patients died within 30 days, and 11.8% within 1 year in the retrospective cohort. Both the short- and long-term survival was significantly impaired in women presenting with perforated duodenal ulcer. The main causes of death at one year were malignancies and cardiovascular diseases. Interestingly, previous use of statins was associated with significant reduction in all-cause mortality. Of all patients admitted for acute upper endoscopy during 2012-2014, 23% had PUD. Other specific diagnoses in acute upper endoscopy were oesophagitis (12%), oesophageal or gastric varices (10%), 10% gastroduodenitis (10%), Mallory-Weiss lesion (8%), and malignancy (5%). Of the PUD patients, 31% were H.pylori positive. The 30-day mortality was very low 0.7%. This is most probably explained by the exclusion of unstable or otherwise fragile patients who were not able to give written informed consent at the admission. The one-year mortality was 12.9% which is in line with results of the retrospective study. Comorbidities were associated with decreased survival (p=0.029) and obesity (BMI>=30) was associated with better survival (p=0.023). Of all individual patients referred for endoscopy, the source for acute bleeding or severe anaemia was not evident in 19% of patients. In further examinations, the diverticular disease of the colon was regarded as the most probable source of bleeding in 39% of patients of these patients. In conclusion, both the incidence and complications of PUD have markedly decreased in Finland. However, the one-year mortality associated with PUD remained high with no change. PUD is still the most common cause of acute gastro-intestinal bleeding.
  • Koivumäki, Tuuli (Helsingin yliopisto, 2018)
    Milk whey proteins, especially α-lactalbumin and β-lactoglobulin, are valuable to human nutrition due to their excellent amino acid composition. For this reason, they are also favored by sports nutrition industry. In food products, proteins often constitute with a desired technological function, such as their water-binding, foaming and emulsifying properties. Oxidative deterioration of proteins alters these properties, and can occur during processing and storage. Perhaps even more importantly, oxidation of proteins can lead to their compromised bioavailability and loss of nutritive value, if the so called essential amino acid residues are affected. In order to evaluate the oxidation status and quality of food proteins, versatile analytical tools are needed. The currently available methods, also used in milk studies, include a very general spectrophotometric measurement of carbonyl compounds which are typically formed by many oxidation reactions. However, the milk whey proteins are particularly rich in amino acids such as cysteine, methionine, tryptophan and tyrosine, which are all known to produce oxidation products other than carbonyl form. More accurate tools are needed to allow a better fit for the different types of proteins, and to expand the understanding of site-specific oxidation reactions. The purpose of this dissertation study was to establish a novel protocol for the investigation of protein oxidation via peptides produced by trypsin digestion. The proteins used in the study were α-lactalbumin and β-lactoglobulin, the two main ingredients of bovine milk whey. The selected peptides were chosen based on their amino acid composition containing at least one residue known to be oxidatively prone. Fractionation was achieved with a developed preparative-HPLC-MS method, and the collected peptides were oxidized individually in metal-catalyzed oxidation (MCO with Fenton chemistry) conditions for 14 days in +37 °C. Furthermore, LC–ESI-QIT-MSn methods including UV/VIS and fluorescence detectors, were created to investigate the site-specific oxidation modifications in the studied peptides. The results gathered in this study showed that carbonyl formation was often secondary to other amino acid oxidation modifications in the chosen peptides. Only 50% of the included lysine residues were observed to oxidize into the most typical carbonyl form, whereas all of the studied methionine residues as well as most tryptophan and cysteine residues were found to be very prone to oxidize. In addition to the confirmed main target sites of MCO, this study proposes several promising peptides that could be used as markers of oxidation for monitoring the oxidative status of full whey proteins. Especially the proposed peptide markers formed from ALPMHIR and LIVTQTMK of β-lactoglobulin as well as LDQWLCEK and VGINYWLAHK from α-lactalbumin were considered highly potential. In addition, the created and proven analysis protocol provides a valuable basis for further investigations of food protein and peptide oxidation and interaction studies.
  • Biskupska, Anna Maija (Helsingin yliopisto, 2018)
    Abstract Verbi verbistä A verb for a verb A comparative study of the semantic structure of derived verb lexicon in Polish and Finnish Anna Maija Biskupska, University of Helsinki, Finland This thesis compares the verb derivation systems of Polish and Finnish on the grounds of their contrastive morphosemantic analysis. As the main database I have used large monolingual dictionaries of both languages and as a theoretical background structural and conceptual semantics. In both languages derivatives form the major part of the verb lexicon.The most crucial semantic categories among the derivatives are verbs describing causative and anticausative change of state events. Nevertheless, the morphosemantic structure of the Polish and Finnish derivatives expressing change of state has essential differences. This particularly concerns deverbal causative and anticausative derivatives. In Polish they are typically created by means of polysemous prefixes of lexical (local-directional) origin or the się reflexive, while Finnish produces them by using suffixes of a generic causative ((t)tA-) or anticausative (U-) meaning. Polish prefixes add to the causative stem verbs not only the meaning of a change of state but also its specified result. Moreover, the prefixes influence the aspect of the stem changing an imperfective stem verb into a perfective derivative. In Finnish, unlike in Polish, deverbal derivatives expressing change of state are not explicitly resultative. Even if derivational suffixes may have an influence on the aspectual features of their stem verbs, there is no grammaticalized verb aspect in Finnish. In Polish it is possible to derivate from a causative verb several resultative causative derivatives by using different prefixes to express different results. This kind of explicit multiresultativeness is alien to Finnish verbs. Accordingly, for both the Polish stem verb and its prefixal derivatives stands often only one Finnish verb, the meaning of which corresponds to the meaning of the Polish multiresultative stem verb and the whole group of its prefixal derivatives. Together with their stem verbs, prefixal derivatives build hierarchical taxonomies based on hyperonym-hyponym relations. This makes the Polish change of state verb lexicon rich in synonyms and its semantic structure deep. Compared with it, the Finnish lexicon is poorer in synonyms and its semantic structure shallower. The semantic differences between Polish and Finnish change of state derivatives reflect not only on the semantic structure of the verb lexicon. They as well come out in the argument structure and lexicalization strategies (patterns). Because of the prefixation, conflation is a very characteristic strategy for Polish, while the strategy Finnish prefers is typically straight. In sum, because of the prefixation Polish derivatives expressing change of state include more semantic and pragmatic information about a situation than Finnish suffixal derivatives. Information encoded in the verbs by prefixation may concern their aspectual features (perfective aspect, lexical aktionsart meanigs), modality, resultativeness, causativeness on the one hand, and semantic roles of the arguments and selection rules on the other hand. In Finnish such information is encoded partly in verbs and partly in their arguments.
  • Suomivuori, Carl-Mikael (Helsingin yliopisto, 2018)
    The efficient absorption and utilization of sunlight is one of the most fundamental processes of life, as it is required both for photosynthesis and for visual perception. Biological light capture occurs through light-sensitive molecules called chromophores, which are embedded in complex protein environments that greatly affect both the wavelength of the absorbed light and the subsequent light-triggered activation process. Despite extensive experimental and theoretical studies of photobiological systems, the molecular mechanisms by which proteins affect the light absorption of biological chromophores remain largely unclear. In this doctoral thesis, we combine large-scale correlated quantum chemical calculations, extensive classical molecular dynamics (MD) simulations, and hybrid quantum mechanics/molecular mechanics (QM/MM) methods to address the light capture in photobiological systems. We employ these computational approaches to study the green fluorescent protein (GFP), photosynthetic reaction centers, as well as both natural and artificial retinylidene proteins. We show how correlated second-order ab initio calculations can be made feasible for large quantum chemical models by employing the reduced virtual space (RVS) and Laplace-transformed scaled opposite- spin (LT-SOS) approximations. Our results uncover intrinsic differences in the excited-state properties of different photosynthetic reaction centers and help determine the color-tuning mechanism of retinal in engineered rhodopsin mimics. Finally, as a result of this work, we propose a mechanism for the ion translocation in the newly discovered light-driven sodium pump, Krokinobacter eikastus rhodopsin 2 (KR2). Elucidating the fundamental physical and chemical principles behind biological light capture is essential for developing, e.g., novel biomarkers, optogenetic tools, and biomimetic catalysts for energy conversion.
  • Ghafar, Abdul (Helsingin yliopisto, 2018)
    Aerogel is a highly porous and lightweight solid material that is prepared by replacing the liquid phase of a gel with air in such a way that the three-dimensional polymeric network remains intact in a dry state. Polysaccharides as aerogel-forming materials have attracted attention over the past few years due to their excellent innate properties, such as their non-toxicity, eco-friendliness, and derivation from renewable resources. Therefore, aerogels from polysaccharides have enormous potential for biomedical, pharmaceutical, and food industrial applications. Formation of the gel is the first step towards the aerogel preparation, though not all polysaccharides tend to form a gel in their native form. It is therefore required to make some modifications to their structures. The choice of modification technique is of the greatest importance in developing polysaccharide-based aerogels for food and food-related applications because the modification technique should be safe. In this thesis, galactose oxidase (GaO) was used as a safe and environmentally friendly modification technique to oxidize and cross-link the polysaccharides guar galactomannan (GM) and tamarind seed xyloglucan (XG). Furthermore, the oxidation ability of GaO and the formation of GM and XG hydrogels were studied in the presence of varying quantities (5–25%) of nanofibrillated cellulose (NFC) as a reinforcing agent to obtain composite hydrogels. The liquid phase of the hydrogels was removed using two different drying techniques: lyophilization and supercritical CO2 (sc-CO2) drying, and the relationship of these techniques to the aerogels’ properties, such as volumetric shrinkage, morphology, specific surface area, and mechanical behavior, were also studied. In this thesis, the synchrotron X-ray microtomography (XMT) technique was used as a modern and non-invasive imaging technique to characterize the aerogels for qualitative and quantitative morphological features in relation to their processing conditions. The enzymatic oxidation of GM and XG with and without NFC-reinforcement allowed for the formation of elastic hydrogels. This study showed that the addition of NFC up to 25% did not hinder the enzymatic activity, and in this way, composite hydrogels were obtained. NFC-reinforcement significantly increased the elastic modulus (Gʹ) as compared to the corresponding plain GM and XG hydrogels, but this effect depended on the type of polysaccharide (GM or XG). Replacing the liquid phase of the hydrogels with solvent also showed the strengthening effect of NFC in relation to the GM hydrogel matrix. NFC reduces the volumetric shrinkage, which is dependent on the type of solvent. The lyophilization drying technique is more efficient in terms of preserving the hydrogel’s original volume when converting to the aerogel, especially as compared to supercritical CO2 drying, which showed significant volumetric shrinkage during the drying process. However, supercritical CO2-dried aerogels displayed mesoporous structures with pores sizes in the range of few nanometers to a few hundred nanometers that resulted in high surface areas up to 330 m2/g of such aerogels. In contrast, lyophilized aerogels displayed different morphologies; for example, the size of the pores ranged from 125 to 250 m, and they exhibited a low surface area (< 10 m2/g). The three-dimensional structures of the studied polysaccharide-based aerogels were successfully visualized. Quantitative data provided a complete range of pore sizes and pore wall thickness distributions that were dependent on the ice-templating methods and NFC reinforcement. In conclusion, this study revealed that the properties of the studied polysaccharide-based composite aerogels depend on processing parameters, the choice of drying techniques, and the addition of a reinforcing agent. The properties of GM- or XG-based aerogels can be tailored to a desired application through the selection of a drying method with carefully controlled processing conditions. XMT proved to be a promising characterization technique for bio-based porous materials for understanding their structural properties in relation to their functional properties.
  • Hirvelä, Jaakko (Helsingin yliopisto, 2018)
    Knowledge requires more than a true belief. In order to know something one must not only believe the truth, rather one’s belief has to be related to its truth in a certain way. One of the principal aims of epistemology, the study of knowledge, is to explain what that ‘certain way’ is. This dissertation examines the idea that knowledge requires a certain modal connection to truth. Such a connection is expressed with a condition that includes modal notions, like ‘would’, ‘must’, ‘could’, ‘might’ etc. Modal notions refer not to how things are, but to how things could have been, should be, must be, or would be. Modalized epistemology is epistemology that seeks to solve epistemological problems with the help of modal notions. The motivation for modalized epistemology stems from the fact that many concepts that have a central place in epistemology seem to be modal in nature. ‘Reliability’, ‘luck’, ‘ability’ and ‘certainty’ are perhaps best explicated with the help of modalities. This thesis develops further an existing modal condition known as the safety condition and applies it to several epistemological problems. According to the safety condition in order to know it must be the case that one could not easily have erred. In Essay 1 a novel way of understanding the safety condition is offered and used to solve two perennial problems in epistemology. In Essay 2 modalized epistemology is applied to the problem of peer disagreement. In Essay 3 it is argued that the modal relation that must hold between a belief and its truth in cases of knowledge cannot be as strong as some virtue epistemologists are inclined to think. The thesis contains also an introductory chapter that offers a brief historical background of the development of modalized epistemology and lays out the current debate as well as some problems that are left unanswered in the essays.
  • Kuukkanen, Mari (Helsingin yliopisto, 2018)
    This study examines the means and ends of the Finnish anarchist movement in the early 2010s. The data consists of ethnographic field notes on various anarchist events, 12 semi-structured interviews and published material from anarchist media outlets. The data is analyzed through three conceptual lenses. First, what kinds of cultural repertoires were available and preferable for the anarchists will be studied. Second, the role of the movement’s collective identity in the coordination of anarchist action is also scrutinized. Third, the study explores what kinds of strategic dilemmas emerged for anarchists and how they were solved. Thus, on one hand, the study aims to analyze movement culture by examining both ‘external’ (repertoires) and ‘internal’ (collective identity) culture and their interplay. On the other hand, cultural analysis is combined with a focus on strategy. The premise is that cultural factors always affect activists’ strategic reasoning. The analysis shows that during the research period, great emphasis was placed on forging a distinctive collective identity for anarchists. Through boundary drawing, central movement actors strived to disassociate anarchism from both leftism in general and the moderate, reform-oriented and expert-driven civic activism, which dominates Finnish civil society. The identity-building effort was mirrored in the preference for characteristically anarchist political practices: prefiguring alternatives to the current social order and rebelling, even with destructive means, against it. However, the embeddedness of the Finnish anarchist movement in the social movement field and the activist networks means that anarchists often act politically in a similar manner to other, less rebellious activists. The fear of being obscured in the midst of ‘regular’ activism fueled the aforementioned boundary drawing. This positioning in relation to other activists contributes to the movement’s relative moderateness as well: in Finland presenting itself as the radical alternative can be achieved by fairly modest means. In the given period, the main strategic dilemmas faced by the movement were so-called ‘resonance or radicalism’ and extension dilemmas. As for the first, although the preference was on radicalism, anarchists occasionally used their strategic capacity for intentionally choosing more culturally resonant means. However, this balancing act was strenuous, and it was reflected in the extension dilemma as well. The anarchists studied found it difficult to answer who constituted the movement’s constituency and for whom mobilization efforts were addressed. Although, in theory, anarchists pursue the self-rule of the ‘people’, in practice, the bond the anarchists in this study prefigured was predominantly that of the ‘chosen few’ whose solidarity was based on a common struggle and shared countercultural values and aesthetics.
  • Arpalahti, Leena (Helsingin yliopisto, 2018)
    The ubiquitin-proteasome system (UPS) is the major cellular pathway for controlled protein degradation, and, together with the autophagy-lysosome pathway, it is a central player in maintaining protein homeostasis. The catalytic core of the UPS is the proteasome, a complex holoenzyme composed of multiple different subunits with varying functions. Disruptions in the UPS are associated with many pathological conditions, including aging-related neurological diseases (such as Alzheimer's, Parkinson's, or Huntington's disease), as well as different cancers. Proteasome inhibitors (e.g. Bortezomib) are in use as cancer therapeutics (e.g. in refractory multiple myeloma and mantle cell lymphoma), but dose-limiting toxicities, drug-resistance and other adverse side-effects have created an acute need for identifying alternative targets that modulate the UPS. Yet, despite its wide-ranging importance, it remains to be defined how UPS is regulated, especially in vivo. The purpose of this thesis was to provide new information on UPS modulation in a living, multicellular organism, with the help of the model organism Caenorhabditis elegans. Further, the aim was to investigate the potential role of an identified proteasome regulator UCHL5/UBH-4 as a biomarker in three gastrointestinal cancers: colorectal cancer (CRC), gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC). In the first part of the study, it was established that UCHL5/UBH-4, a proteasome-associated deubiquitinating enzyme (DUB), modulates proteasome activity in C. elegans, and additionally increases the degradation of proteotoxic proteins in human cancer cells. In C. elegans, UBH-4 expression was demonstrated to be regulated by the ageing-regulating Insulin/IGF-1 signaling (IIS) pathway through the transcription factor DAF-16 in a tissue-specific manner. Further, minor knockdown of ubh-4 resulted in a short lifespan extension without affecting progeny amounts. In the second part of the study, the role of UCHL5 was investigated in various gastrointestinal cancers. UCHL5 tumorexpression was scored with immunohistochemistry from representative patient tumor samples in CRC, GC and PDAC. UCHL5-immunoexpression correlated with increased survival in the subgroup of patients with lymph node-positive (Dukes C/stage III) rectal cancer. In addition, both positive nuclear and high cytoplasmic UCHL5-immunoexpression associated with better prognosis in PDAC. Positive UCHL5-immunoexpression was also linked to enhanced survival in the subgroups of gastric cancer patients with small tumors (<5 cm) or stages I-II of the disease. This thesis identified UCHL5/UBH-4 as a new proteasome modulator, and further UCHL5 as a novel prognostic marker with potential clinical relevance. In the future, the recognized significance of UPS in the development and progress of different diseases is only likely to grow. Therefore, understanding the underlying regulatory mechanisms of UPS function is of fundamental importance.
  • Ling, Jiaxin (Helsingin yliopisto, 2018)
    More than 60% of human emerging infectious diseases (EIDs) are zoonotic. Zoonoses are infectious diseases of animals (usually vertebrates) that can be transmitted to humans. Hantaviruses are emerging zoonotic pathogens that belong to the genus Orthohantavirus and family Hantaviridae in order Bunyavirales. Hantaviruses pose a serious threat to human health because their infection causes two highly fatal diseases: haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). Rodents have been regarded as the main reservoir and evolutionary scene of hantaviruses. In the last three decades, our knowledge of hantaviruses has broadened significantly. In contrast to the initial assumption that hantaviruses are mainly carried by rodents, many novel hantaviruses have been detected in shrews, moles and bats during the last few years. These findings raise a number of significant questions about the evolutionary history of hantaviruses, their host association and adaptation, the role and frequency of spillover infections and host-switch events, and most importantly, their pathogenicity.   In Finland, Puumala virus (PUUV) has been regarded as the only rodent-borne hantavirus present in the country. To search for novel hantaviruses other than PUUV, various novel hantaviruses were molecularly identified in different species of Soricomorpha ("shrew-form"). Genetic analyses revealed that four soricomorph-borne hantaviruses circulate in Finland, including Boginia virus (BOGV) in Neomys fodiens and Asikkala virus (ASIV) in Sorex minutus. Common shrews (Sorex araneus) harboured two different hantaviruses: Seewis virus (SWSV) and an Altai-like virus, showing the first evidence of co-existence of two distinct hantavirus species circulating simultaneously in one host species population. This host sharing of two divergent hantaviruses in the European common shrews contradicts hantavirus-host specificity, further implying the complexity of hantavirus evolution.   After screening hundreds of S. araneus from all of Finland, we obtained a large data set of new SWSV sequences that enabled phylogeographic analyses of SWSV. The results demonstrated that this shrew-borne hantavirus is similar to rodent-borne hantaviruses, and the post-glacial spread of SWSV into Finland mirrors that of the host, S. araneus: these shrews colonized Finland from the east after the last ice age (12,000–8,000 years ago) and then subsequently spread along emerging land bridges towards the west or north.   Most new hantaviruses discovered in soricomorph and bat hosts instead of rodents have raised questions as to whether any of them will emerge as human pathogens. Therefore, to predict human exposure risk, novel laboratory techniques for molecular and serological hantavirus detection were developed. No evidence of SWSV infection was found among a panel of 486 patient serum samples; however, we demonstrated a cross-reaction of anti-PUUV serum with shrew-borne hantavirus nucleocapsid (N) protein.   This thesis focused on the diversity, host maintenance and cross-species transmission dynamics of soricomorph-borne hantaviruses. The study presented innovative methods to investigate this pertinent topic at the interface of wildlife diseases and human health. The results provided new insights about the ecology, evolutionary origins and phylogeography, and most importantly, the potential pathogenicity of soricomorph-borne hantaviruses. This knowledge in combination with future studies will hopefully lead to a better understanding of host-parasite relationships.