Väitöskirjat

Recent Submissions

  • Venhoranta, Heli (Helsingin yliopisto, 2015)
    Dairy cattle breeding programs rely heavily on artificial insemination (AI). The AI enables intense selection for desired traits, but the use of few elite bulls carries a risk that inherited defects may proliferate in the population. The emergence of inherited defects is a recurrent issue in cattle breeding and rapid identification and management of genetic defects are crucial for preventing economic losses and maintaining good animal welfare. Modern molecular genetics techniques enable efficient detection of causative mutations, information which is needed for DNA testing. In this study, we investigated three inherited congenital bovine defects and located causative mutations for these diseases. 1. A microdeletion in PEG3 domain causes intrauterine growth restriction and stillbirths to almost half of the pregnancies sired by a single Ayrshire AI bull. The deletion, when inherited from the sire, is semi-lethal but the female mutation carriers can breed normally. The deletion truncates the 3 end of the non-coding maternally imprinted MIMT1 transcript and also causes expression changes in other genes of the domain. The expression changes of hundreds of genes in the foetal side of the placenta were also demonstrated. 2. Inherited gonadal hypoplasia with incomplete penetrance in Northern Finncattle and Swedish Mountain breed is associated with homozygosity for the Cs29 allele. This allele is an ectopic segment that is duplicated and translocated from chromosome 6 to 29 and encompasses the KIT gene. Cs29 allele is associated with colour sidedness in various cattle breeds, which coheres with the results that gonadal hypoplasia is connected with white coat colour. The KIT gene is known to regulate the migration of the germ cells and precursors of melanocytes. 3. A new recessive developmental disorder defined as PIRM (ptosis, intellectual disability, retarded growth and mortality) in Ayrshire breed was associated with single base substitution in the UBE3B gene. Mutation causes in-frame exon skipping, resulting in an altered protein lacking 40 amino acids, which likely comprises protein function. In humans, mutations in the UBE3B gene are associated with Kaufman oculocerebrofacial syndrome, with similar pathological effects as for PIRM syndrome. The UBE3B mutation may be connected with the AH1 haplotype, which is associated with reduced fertility and has a carrier frequency of 26.1% in the North American Ayrshire population. The mutations related to these three defects or syndromes can now be easily tested for. The results can be used to avoid risky matings, cull carriers and provide a veterinary diagnostic. The expression analyses proved that the mutations in Ayrshires also affected the RNA expression of the respective mutated gene or even hundreds of other genes. The described genotype-phenotype associations can be used as a basis for approaches to locate quantitative trait loci in cattle or provide new insights into developmental biology and inform translational research across species.
  • Louhimo, Riku (Helsingin yliopisto, 2015)
    Cancer is one of the leading causes of death in industrialized nations and its incidence is steadily increasing due to population aging. Cancer constitutes a group of diseases characterized by unwanted cellular growth which results from random genomic alterations and environmental exposure. Diverse genomic and epigenomic alterations separately and jointly regulate gene expression and stimulate and support neoplastic growth. More effective treatment, earlier and more accurate diagnosis, and improved management of cancer are important for public health and well-being. Technological improvements in data measurement, storing and transport capability are transforming cancer research to a data-intensive field. The large increases in the quality and quantity of data for the analysis and interpretation of experiments has made employing computational and statistical tools necessary. Data integration - the combination of different types of measurement data - is a valuable computational tool for cancer research because data integration improves the interpretability of data-driven analytics and can thereby provide novel prognostic markers and drug targets. I have developed two computational data integration tools for large-scale genomic data and a simulator framework for testing a specific type of data integration algorithm. The first computational method, CNAmet, enhances the interpretation of genomic analysis results by integrating three data levels: gene expression, copy-number alteration, and DNA methylation. The second computational method, GOPredict, uses a knowledge discovery approach to prioritize drugs for patient cohorts thereby stratifying patients into potentitally drug-sensitive subgroups. Using the simulator framework, we are able to compare the performance of integration algorithms which integrate gene copy-number data with gene expression data to find putative cancer genes. Our experimental results indicate in simulated, cell line, and primary tumor data that well-performing integration algorithms for gene copy-number and expression data use and process genomic data appropriately. Applying these methods to diffuse large B-cell lymphoma, integrative analysis of copy-number and expression data helps to uncover a gene with putative prognostic utility. Furthermore, analysis of glioblastoma brain cancer data with CNAmet suggests that a number of known cancer genes, including the epidermal growth factor receptor, are highly expressed due to co-occuring alterations in their promoter DNA methylation and copy-number. Finally, integration of publicly available molecular and literature data with GOPredict suggests that treating patients with FGFR inhibitors in breast cancer and CDK inhibitors in ovarian cancer could support standard drug therapies. Collectively, the methods developed here and their application to varied molecular cancer data sets illustrates the benefits of data integration in cancer genomics.
  • Kajos, Maija (Helsingin yliopisto, 2015)
    Vast amount of volatile organic compounds (VOCs) are emitted into the atmosphere from various natural and manmade sources. VOCs have an important role in the atmospheric chemistry. They participate in ozone production in the planetary boundary layer and affect the oxidation capacity of the atmosphere. VOCs also contribute to the formation and growth processes of atmospheric aerosol particles, which, once large enough, can act as a cloud condensation nuclei (CCN) and influence the climate by altering the properties of clouds. Globally, VOC emissions from forest vegetation are dominating over the other sources. The circumpolar boreal forests cover more than 35% of the Earth s total forested area, making it one of the biggest biomes on planet. This thesis focuses on the biogenic VOCs in the boreal forests with regard to their shoot scale emissions to their role in the atmosphere. First, the VOC emissions of two different Larix species, L. cajanderi and L. sibirica, were measured and reported quantitatively for the first time. Larix species are the predominant trees in large parts of the Siberian forests, where the climate is too harsh for other tree species to grow. The emissions of both examined Larix species were dominated by monoterpenes similarly to other tree species with comparable emission potentials. Second, a protocol for proton transfer reaction mass spectrometer (PTR-MS) was developed for calibration and data processing of long-term and stand-alone VOC measurements. The reliability of this protocol was tested by comparing simultaneous VOC measurements of two PTR-MS and two gas chromatograph mass spectrometers (GC-MS). The detection of five compounds was analyzed in depth and strengths and weaknesses of the measurements were highlighted. Third, the increase in biogenic VOC and CCN concentrations was investigated in connection with the global warming. This was done by analyzing long-term data of concentrations and compositions of aerosol particles and their biogenic precursor VOCs in different environments. A negative aerosol-climate feedback, driven by the increase of BVOC emissions due to climate warming, was hypothesized and found.
  • Bourbia, Nora (Helsingin yliopisto, 2015)
    The central nucleus of amygdala (CeA) is known to be involved in pain and nociception, but the mechanisms or its role in descending control of pain-related behavior is poorly understood. The aim of this study was to investigate the involvement of the neuropeptide corticotropin-releasing factor (CRF) and the glutamatergic system of the CeA in pain and nociception in healthy control animals and in an animal model of chronic neuropathic pain induced by spared-nerve injury (SNI). Two aspects of pain were studied: emotional-like pain behavior was assessed by using the aversive place-avoidance paradigm and sensory-discriminative was assessed by determining the mechanical limb-withdrawal threshold and the thermal (heat) limb-withdrawal latency. Moreover, the aims were to determine whether medullospinal serotoninergic pathways and the midbrain periaqueductal grey (PAG), respectively, were involved in relaying pain-modulation induced by the CeA in SNI and healthy control animals. Additionally, hemisphere of the CeA and submodality of pain stimulus were among studied parameters. Surgical procedures and electrophysiological recordings were performed under general anesthesia. The studies on the role of the CeA in the emotional-like aspect of pain in SNI rats revealed that activation and blocking of the group I metabotropic glutamate receptors (mGluRs) facilitates and inhibits, respectively, the aversive aspect of pain. Furthermore, increase of endogenous CRF as well as blocking glutamatergic N-methyl-D-aspartate (NMDA) receptors in the CeA reduced the aversive aspect of neuropathic pain. The studies on the sensory-discriminative aspect of pain revealed that an increase of endogenous CRF in the CeA is pronociceptive in both control and SNI rats. CeA injection of a high dose of glutamate had a mechanical antinociceptive effect that was mediated by NMDA receptors in healthy but not SNI rats. A low dose of glutamate had a pronociceptive effect mediated by NMDA receptors in SNI rats. Furthermore, tonic descending pronociception induced by NMDA receptors and the mGluR1 in the CeA contributes to the maintenance of neuropathic hypersensitivity. The investigation on the role of serotonergic neurons of the rostroventromedial medulla (RVM) in modulation of spinal nociception by amygdaloid glutamate in SNI rats indicated that the RVM is a relay for both descending pro- and antinociceptive effects from the CeA. The investigation on the role of the PAG in the descending control of nociception induced by glutamate in the CeA of healthy rats indicated that the PAG is a relay in the descending control of nociception induced by amygdaloid glutamate. Furthermore, the right-hemispheric lateralization of the pronociceptive effect by amygdaloid CRF in controls was lost in SNI rats. However, descending antinociception induced by the glutamatergic system of the CeA showed no hemispheric lateralization in healthy controls; a high dose of glutamate in both the left and right CeA induced equal attenuations of mechanical and thermal nociception, which effects were, respectively, NMDA-dependent and NDMA-independent.
  • Terhonen, Eeva-Liisa (Helsingin yliopisto, 2015)
    Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) cover large areas in boreal regions with significant economic importance to Finnish forest industry. Approximately 15% of the spruce trees felled in Finland are rotten and thus commercially less valuable. The majority of this conifer wood decay is due to the root and butt rot pathogen Heterobasidion annosum sensu lato. Extensive logging of conifer forests has changed the environment into favouring this pathogen in stands where it originally has been rare. The saprotrophic fungus Phlebiopsis gigantea has for several years been used as a biocontrol agent against H. annosum s.l. in spruce and pine stumps. A major problem is that, although the effectiveness of P. gigantea as a biocontrol agent has empirically been shown, the long-term biological effect of this fungus on other decomposing wood microbiota has not been proven. The first objective of this thesis is to evaluate the impact of the only biocontrol agent used against root and butt rot fungus (H. annosum s.l.) on other resident microflora of Norway spruce stumps. An additional objective is to screen and identify other potentially novel bioagents that can be deployed for the biocontrol of the conifer pathogen. To find out whether the P. gigantea treatment impacts the overall diversity of other non-target stump microbes we used the 454- pyrosequencing approach. Samples were collected from forest sites previously pre-treated with P. gigantea either one, six or 13 years ago. Similarly samples were collected from untreated stumps within the same forest site over the same period of time. The results revealed that initial application of the biocontrol agent influenced the fungal species composition, but the overall fungal diversity was not affected and no statistical differences were observed between treated and non-treated stumps in the mycobiota. The biocontrol treatment significantly decreased the initial bacterial richness in the stumps, but the bacterial community gradually recovered and the negative effect of P. gigantea was attenuated. In parallel to the above studies, I further explored the potential of finding other novel biocontrol agents for use in managing the disease caused by the root rot pathogen Heterobasidion parviporum. This necessitated isolation studies of fungal root endophytes from forestry sites such as pristine mires and drained peatlands where the spread of H. annosum s.l. species have not been commonly reported. A total of 113 isolates of fungal root endophytes were obtained from non-mycorrhizal P. abies roots, which were assigned to 15 different operational taxonomic units (OTUs). Nineteen of the isolates (17%) inhibited the growth of the conifer root rot pathogen in vitro. From these, two isolates were further used to test the potential inhibitory effects during interaction, in vitro, with H. parviporum. Additionally, the metabolites secreted by the selected root endophytes were extracted and the inhibitory effects on these pathogenic fungi were assayed. The secreted metabolites were further chemically analysed using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). These results give new information from the new possibilities to protect the valuable seedling roots from root rot. The results of the thesis provide new information to facilitate better management and protection of these forest sites from H. annosum s.l. as well as support the continued used of P. gigantea for stump pre-treatment in Finnish forests.
  • Autio, Karoliina (Helsingin yliopisto, 2015)
    Cancer is one of the most common reasons for death in dogs, cats and humans. New therapeutic modalities are necessary to improve disease outcome. One promising approach is oncolytic virotherapy. Until now, the only oncolytic virus evaluated in a clinical trial in veterinary medicine has been canine oncolytic adenovirus, but a clinical trial has been started with oncolytic vaccinia virus (VV) in pet dogs. In cats, oncolytic viruses have not been evaluated in clinical settings. Tumour treatment in dogs and cats could also serve as a model for human cancer therapy. The purpose of the thesis was to evaluate preclinically whether genetically modified oncolytic VV and Semliki Forest virus (SFV) could offer a new treatment modality for dogs and cats. Oncolytic VV was rendered tumour selective by a dual ablation of vaccinia growth factor and thymidine kinase, making it more cancer-specific than previously used VVs in veterinary research. To further increase the efficacy of the VV, an immunostimulatory gene, CD40L, was added to the virus backbone. Avirulent SFV A7(74) has a natural trophism for cancer cells and was not genetically manipulated. Both viruses infected and killed tested cancer cell lines, and VV also infected most of the primary surgical tumour tissues tested. In the nude mouse xenograft model, double deleted VV (vvdd) significantly reduced tumour growth. Interestingly, when in intact monolayers, SCCF1 cells were not killed by VV, but secreted infectious, morphologically abnormal virions. One dog experienced a possible seizure after VV administration, but no other serious adverse events occurred. Vaccinia DNA declined quickly in the blood after virus administration, but was still detectable one week later by qPCR. Only samples taken directly after the VV infusion contained infectious virus, which was not found in any other blood, saliva, urine or faecal samples. Necropsies did not reveal any pathological changes associated with virus administrations. In conclusion, our results show that oncolytic VV and SFV can infect and kill tested canine cancer cell lines, and that VV has antitumoral activity in the mouse xenograft model and it can infect fresh tumour biopsies. In addition, intravenous administration of the viruses did not induce life-threatening adverse events in healthy dogs. These agents thus warrant further evaluation in veterinary medicine.
  • Parnov Reichhardt, Martin (Helsingin yliopisto, 2015)
    To live a healthy life, humans need to co-exist with foreign organisms. These consist of the thousands of different types of microbes that colonize the human body. But also, in the case of a pregnant woman, the fetus can be viewed as a foreign organism. To avoid disease, the barriers of the human body, e.g. the mucosal surfaces, must be maintained. Here the innate immune defense system plays an important role. The salivary scavenger and agglutinin (SALSA), also known as gp340, DMBT1 and SAG, is a molecule found at most mucosal surfaces. SALSA is associated with the epithelium or secreted into the lining fluids, such as tears, saliva and mucus in the respiratory tract. SALSA is known to bind and agglutinate a broad spectrum of bacteria, as well as viruses, and thus play a role in the innate immune defense against invading microbes. The effect of SALSA is mediated in concert with several other defense molecules such as IgA, surfactant proteins A and D, and the complement component C1q. These have all been shown to be ligands of SALSA. Alongside the role of SALSA in innate immunity, evidence for a function in epithelial and stem cell differentiation has emerged. This thesis work has addressed the function of SALSA in innate immunity, especially in early life. SALSA was found in the amniotic fluid and in meconium and feces of newborns. In fact, SALSA was among the most abundant proteins in the intestines of newborn children. By comparing the SALSA protein in the different samples we found size polymorphisms, varying from one individual to another, but also from compartment to compartment within the same individual. These differences were found to alter the ability of SALSA to bind known endogenous and bacterial ligands. SALSA was also found to be expressed in the human placental and decidual tissues. In the 1st trimester of pregnancy, SALSA was detected sporadically in maternal decidual capillaries. Closer to term SALSA was found to be expressed by the syncytiotrophoblast layer of the placental villous trees. In certain sites, e.g. at disrupted and damaged areas of the syncytium, SALSA was found deposited into fibrinoid formations. It partially co-localized with the fibrinoid component fibronectin. Complement activation has been observed at the feto-maternal interface of both healthy and complicated pregnancies. SALSA had previously been found to bind C1q. Thus, it was of interest to investigate the ability of SALSA to interact directly with the complement system. We found that SALSA bound to both mannan-binding lectin and to some extent to all three ficolins (H, L and M). SALSA activated complement, when it was bound to a surface. In contrast, fluid-phase SALSA was able to inhibit the deposition of complement on SALSA non-binding microbial surfaces. It thus acted in dual fashion to target complement attack. In the human placenta we observed C1q-targeting of the SALSA-positive fibrinoid formations. C1q and complement are known to function in the clearance of apoptotic cells and debris. Thereby SALSA and complement probably have a cooperative function in the containment and clearance of the injured structures, thus linking its innate immune activity with the maintenance of tissue homeostasis.
  • Tokariev, Anton (Helsingin yliopisto, 2015)
    In humans the few months surrounding birth comprise a developmentally critical period characterised by the growth of major neuronal networks as well as their initial tuning towards more functionally mature large-scale constellations. Proper wiring in the neonatal brain, especially during the last trimester of pregnancy and the first weeks of postnatal life, relies on the brain’s endogenous activity and remains critical throughout one’s life. Structural or functional abnormalities at the stage of early network formation may result in a neurological disorder later during maturation. Functional connectivity measures based on an infant electroencephalographic (EEG) time series may be used to monitor these processes. A neonatal EEG is temporally discrete and consists of events (e.g., spontaneous activity transients (SATs)) and the intervals between them (inter-SATs). During early maturation, communication between areas of the brain may be transmitted through two distinct mechanisms: synchronisation between neuronal oscillations and event co-occurrences. In this study, we proposed a novel algorithm capable of assessing the coupling on both of these levels. Our analysis of real data from preterm neonates using the proposed algorithm demonstrated its ability to effectively detect functional connectivity disruptions caused by brain lesions. Our results also suggest that SAT synchronisation represents the dominant means through which inter-areal cooperation occurs in an immature brain. Structural disturbances of the neuronal pathways in the brain carry a frequency selective effect on the functional connectivity decreasing at the event level. Next, we used mathematical models and computational simulations combined with real EEG data to analyse the propagation of electrical neuronal activity within the neonatal head. Our results show that the conductivity of the neonatal skull is much higher than that found in adults. This leads to greater focal spread of cortical signals towards the scalp and requires high-density electrode meshes for quality monitoring of neonatal brain activity. Additionally, we show that the specific structure of the neonatal skull fontanel does not represent a special pathway for the spread of electrical activity because of the overall high conductivity of the skull. Finally, we demonstrated that the choice of EEG recording montage may strongly affect the fidelity of non-redundant neuronal information registration as well as the output of functional connectivity analysis. Our simulations suggest that high-density EEG electrode arrays combined with mathematical transformations, such as the global average or current source density (CSD), provide more spatially accurate details about the underlying cortical activity and may yield results more robust against volume conduction effects. Furthermore, we provide clear instruction regarding how to optimise recording montages for different numbers of sensors.
  • Lepojärvi, Jason (Helsingin yliopisto, 2015)
    C. S. Lewis (1898-1963) was one of the most influential Christian thinkers of the twentieth century with continuing relevance into the twenty-first. Despite growing academic interest in Lewis, many fields of inquiry remain largely unmapped in Lewis scholarship today. This compilation dissertation, consisting of an introductory overview together with four stand-alone but connected essays, extends critical understanding of Lewis's contribution to the theology of love. In three of the four essays, Lewis's theology of love is compared to and contrasted with that of Anders Nygren (1890-1978); and in one, that of Augustine of Hippo. Using systematic textual analysis, the essays evaluate Lewis's key concepts, argumentation, and presuppositions. Nygren, the Swedish Lutheran theologian and bishop of Lund, has virtually dominated modern theological discussion of love. His antithesis between selfless and gratuitous Christian love and self-seeking and needful Pagan love, or agape and eros respectively, became enormously influential in twentieth century theology. Lewis was initially shaken up by Nygren's work, and it took him decades to formulate his own model, above all in Surprised by Joy (1955) and The Four Loves (1960). It is shown that Lewis constructed not only his theology of love, but also his theology of spiritual desire as a form of love, in conscious opposition to Nygren. Lewis's theology of love challenges the denigration of eros and its separation from agape. Nygren's predestinarianism is also rejected. Lewis devises his own vocabulary, avoids the use of eros and agape in Nygren's sense, and hardly ever mentions Nygren by name. All this suggests a deliberate apologetic strategy to bypass certain defences of his readers and to avoid Nygren-dependency. Despite their incommensurate love-taxonomies, Lewis's need-love/gift-love and Nygren's eros/agape have often been treated as parallels. This longstanding assumption is shown to be in need of greater nuance. The study demonstrates that Lewis's concept of spiritual longing, which he calls Joy, is relevant to the Nygren debate and serves as a potent variant for Nygren's eros. However, no one thing in Lewis's mental repertoire can serve as a perfect translation of Nygren's eros, because for Lewis it is an abstract caricature cut off from real life. In Lewis's theological vision, contra Nygren, spiritual longing, far from obfuscating the Gospel, is a God-given desire that prepares the way for it. Lewis is not free from the occasional hyperbole or blind spot. For instance, his argument that romantic love is not eudaimonistic is shown to be somewhat convoluted, and his famous disagreement with Augustine is possibly based on a misunderstanding. A perennial feature in Lewis's understanding of love, reflected in all four essays, is the ambiguity of love. Love is not something pejorative, but neither is it an infallible moral compass. God is love, but love is not God.
  • Koskinen, Inkeri (Helsingin yliopisto, 2015)
    This dissertation examines the effects of a change in the roles that extra-academic agents have in academic research: they are participating in the production of academic knowledge more actively than used to be the case. The focus is mainly on disciplines that fall under the umbrella of cultural research. Former informants are nowadays often becoming collaborators, co-researchers or co-authors in collaborative or participatory projects, or conducting activist research on their own cultures. Cultural research is in a unique position when facing the contemporary urge towards more "democratic" knowledge production. In disciplines such as anthropology, folkloristics and ethnology, researchers have always interacted with their informants' knowledge systems and developed research practices for approaching these systems. These practices are presently colliding with new demands that arise from the now common call for collaborative and participatory research. I focus on normative epistemic questions related to relativistic research practices and to objectivity. When the roles of the extra-academic agents change, the composition of research communities is also changed. An interactive notion of objectivity has recently been defended in social epistemology. It takes a research community as the unit whose objectivity is to be assessed. In the articles I identify shortcomings in the interactive objectivity of the emerging research communities, and develop analytical tools that can hopefully be of use in improving the situation. As the composition of research communities is changed, the established ways of approaching extra-academic knowledge systems also have to change. The moderately relativistic practice of avoiding the appraisal of alien knowledge systems is no longer as practicable as it used to be. When former informants join research teams in participatory projects, or indigenous activists become activist researchers, they become part of communities whose interactive objectivity can and should be assessed. This is the case even if some or all of the members of the communities are taken to represent, or see themselves as representing, extra-academic knowledge systems. The contributions of everyone belonging to a research community must be met with the same critical attitude, or the objectivity of the community will suffer.
  • Sandboge, Samuel (Helsingin yliopisto, 2015)
    Background. A small birth size, an indicator of a suboptimal intrauterine environment, is a risk factor for several non-communicable diseases (NCDs), a risk that in many cases is modified by childhood growth patterns. Regional variation in NCD prevalence could partly have its origin in early development. Lifestyle factors further influence NCD prevalence. Aims. We aimed to explore the associations between early growth and adult resting metabolic rate (RMR), body composition, non-alcoholic fatty liver disease (NAFLD), and hypertension. We also studied the associations between fructose intake and NAFLD, and differences in birth size between Helsinki and the Åland Islands. Subjects and methods. The Helsinki Birth Cohort Study consists of 13345 individuals born in Helsinki in 1934‒44. Detailed records are available for all participants including information on maternal and birth characteristics and measurements of childhood body size. 2003 individuals participated in a clinical study in 2001‒04 and 1083 of these additionally participated in a follow-up study in 2006‒08. The Åland records include 1697 births for the years 1937‒44. Results. The association between birth weight and RMR was inverse among women and quadratic among men. A higher attained adult weight than expected, based on weight and height measurements before age 11 years and adult height, was associated with higher adult body fat content. The odds ratio (OR) for NAFLD was 18.5 (95% CI 10.1; 33.6) among those who belonged to the lowest BMI tertile at age 2 years and subsequently were obese as adults, compared to those who were still lean or normal weight as adults. NAFLD was most common among individuals with the lowest dietary fructose intake. Systolic blood pressure (SBP) and the presence of hypertension were inversely associated with linear (height) growth between ages 2 and 11 years. Relative weight gain after age 11 years was positively associated with SBP. Ålandic babies born 1937‒44 were 87 grams (95% CI 61; 111) heavier and 0.4 cm (95% CI 0.3; 0.5) longer than their Helsinki peers. Conclusions. A more pronounced increase in relative weight after age 11 years than would be expected from previous body size, was positively associated with body fat content, NAFLD, and hypertension. Conversely, several growth measurements before age 11 years were negatively associated with the outcomes studied. None of the studied individuals were obese in childhood. Instead, a larger relative childhood body size in this group most likely represents a more beneficial childhood environment. Contrary to previous findings, we found that individuals with the highest fructose intake were least likely to suffer from NAFLD. We found a small but significant difference in birth size between the Åland Islands and Helsinki for the years 1937‒44.
  • Lehtonen, Heini (Helsingin yliopisto, 2015)
    This thesis examines language use in interaction among adolescents in two junior high schools in Eastern Helsinki. The pupils represent several ethnic backgrounds, and some twenty different first languages are spoken in the schools. The thesis analyses the ways in which the adolescents position themselves and each other with regard to social categories related to ethnicity, gender, and style, focusing on the linguistic resources used in the positioning. The attitudes vis-a-vis linguistic diversity and asymmetry are explored as well. The research questions are as follows: 1) How does a linguistic feature become a social indexical? 2) How do (linguistic) styles get enregistered? 3) How are ownership and foreignness of language negotiated and construed? The thesis participates in the current discussions on ways of conceptualizing multilingualism in the globalization era. Questions of immigration and second language acquisition, learning and teaching are discussed from a sociolinguistic point of view. Theoretically and methodologically, the thesis encompasses the fields of linguistic ethnography, interactional sociolinguistics, and the sociolinguistics of globalization. The data consist of 1) field notes and a field diary, 2) recorded interviews with 37 adolescents, 3) several audio and video recordings of spontaneous interaction during both the lessons and the breaks, and 4) retrospective interviews. The analysis shows the adolescents orientating to the categories of Finns and foreigners , but the meaning of these categorizations is construed in local stylistic practices and does not necessarily resemble to the similar labels used in public discourses. Ethnicity, gender, and enregistered styles (such as hip hop) intertwine in such ways, that the participation in local stylistic practices may guarantee a stronger ownership of linguistic resources than one s ethnic background. All types of linguistic features (phonetic, prosodic, morphological, syntactic, lexical) were found to function as social indexicals. Frequent resources that stand out and establish social relationships between participants are especially likely to develop into social indexicals. As a part of local social practices and in the metapragmatic accounts commenting the practices, linguistic features get associated to specific social personae and their characteristics, and get enregistered to styles. Social indexicals are employed in stylized performances that bring another s voice into the interaction. The stylisations serve as a resource for stance-taking, but also as metapragmatic accounts of the features employed in them. The questions of who knows Finnish or does not know Finnish are negotiated both explicitly and implicitly. One of the implicit means of such negotiations are the stylized bad Finnish performances, where the adolescents carnevalize the stereotypical representations of immigrants or non-native Finns .
  • Selim, Shaimaa (Helsingin yliopisto, 2015)
    The objective of the research described in this thesis was to increase the understanding of the transcriptional adaptations of genes encoding proteins, which have key roles in lipid and glucose metabolism, insulin signalling and inflammation, in situations of overfeeding energy during the dry period in dairy cows and summer grazing season in mares. Emphasis was placed on the potential to decrease metabolic disorders and to improve animal nutritional management and health. In the experiment I, dairy cows were fed a grass silage based diet either on a controlled energy level (on average 99 MJ/d metabolizable energy (ME), n = 8) during the last six weeks of the dry period or high energy level (on average 141 MJ/d ME, n = 8) for the first three weeks and then gradually decreasing energy allowance during three weeks to 99 MJ/d ME by parturition. In experiment II, dairy cows were fed ad libitum either grass silage (144 MJ/d ME, n = 8) or a mixture of grass silage, wheat straw and rapeseed meal (TMR, 55%: 40%: 5%, 109 MJ/d ME, n = 8) during the 8-wk dry period. Liver and adipose tissue biopsies and blood samples were collected during the transition period in experiments I and II. In the experiment III, the impact of grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland pasture (NG) on fat deposition, insulin resistance status and adipose tissue gene expression of Finnhorse mares was studied. Body measurements, intravenous glucose tolerance tests (IVGTT), and sampling for the determination of neck and tailhead adipose tissue gene expressions were conducted in May and September. In experiments I and II, overfed cows had greater total dry matter and ME intakes and ME balance before parturition than control cows, but no differences were observed after calving. Increases in body weight and body condition score were greater in the overfed cows of the experiment II during the dry period. In the experiment I, there was greater plasma insulin and lower glucagon/insulin ratio in overfed cows than in control cows, while in the experiment II, there were no differences in blood parameters between overfed and TMR group during the transition period. Down-regulation of key genes linked to hepatic gluconeogenesis and fatty acid β-oxidation in the overfed group of cows in the experiment I was found, suggesting impaired liver function compared to a controlled energy diet. In the experiment II, ad libitum feeding of grass silage throughout the dry period may have attenuated the increase of hepatic gluconeogenic capacity from propionate compared to a controlled TMR diet. However, there was no difference in the expression of genes related to hepatic glucose release during the transition period (II). In adipose tissue, there was some evidence that the level of energy overfeeding may have exacerbated the inflammatory status postpartum and temporarily decreased lipogenesis very near parturition relative to control energy diet (I). In the experiment II, prepartal ad libitum feeding of grass silage decreased lipogenesis and insulin sensitivity early postpartum compared to the TMR control group. In the experiment III, CG mares had higher median body condition score and body weight, and larger waist circumference than NG mares at the end of grazing. In September, greater basal and peak insulin concentrations, and faster glucose clearance rate during IVGTT were observed in CG mares than in NG mares. In addition, a greater decrease in plasma non-esterified fatty acids during IVGTT was noticed in CG mares. There were no differences in the expression of genes related to insulin resistance, inflammation and lipogenesis between the two groups. Significant temporal differences in the expression profiles of genes related to insulin resistance and lipogenesis were observed during the grazing season. Grazing on CG had moderate effects on responses during IVGTT, but did not exacerbate insulin resistance. In conclusion, overfeeding energy with concomitant weight gain moderately altered the expression of genes related to insulin resistance, inflammation and lipogenesis in adipose tissue of dairy cows. Prepartal overfeeding energy affected the expression of genes related to hepatic gluconeogenesis and fatty acid oxidation in dairy cows, but the extent of these effects differed depending on the dietary composition during the close-up period (e.g. feeding of cereal grain). In mares, the diets with variable energy content did not affect the expression of insulin resistance- or inflammation-related genes, although mares were different in their body condition scores.
  • Pekkonen, Pirita (Helsingin yliopisto, 2015)
    Human tumorigenesis is a process in which a normal cell needs to acquire multiple characteristics to become malignant and metastatic. In short, these so called cancer hallmarks include increased proliferation and cell survival, as well as the ability to invade into the surroundings, induce angiogenesis, and finally metastasize to distant sites. These traits are regulated in a variety of different ways. However, some embryonic signaling pathways, including the Notch pathway, are able to regulate many of these processes. Furthermore, it has been shown that these signaling pathways can be deregulated in cancer, and that their untimely activation can lead to malignancies. In this study, Kaposi's sarcoma herpesvirus (KSHV) associated malignancies, namely Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), as well as melanoma have been used as model cancers. In all these malignancies, the tumor cells show alterations in cell identity and lineage marker expression, i.e. signs of cellular de- or transdifferentiation. In addition, the Notch pathway has been shown to be overly active in all of them. Thus, this thesis has focused on how the pro-tumorigenic traits are affected by cell plasticity and reprogramming in these cancers, and how the signaling pathways leading to these phenotypes, most notably Notch, are in turn regulated. Firstly, the results show that in vivo expression of a KSHV oncogene, viral (v-)cyclin, leads to activation of Notch signaling through Notch3 upregulation as well as fine-tuning of the NF-κB pathway through Cdk6 mediated phosphorylation. These changes in turn lead to defects in T-lymphocyte differentiation and immune functions, as well as to the development of T-cell lymphomas. Secondly, this work demonstrates that KSHV infection in primary lymphatic endothelial cells (LECs) in three dimensional (3D) cell culture model leads to activation of a morphogenic process, endothelial to mesenchymal transition (EndMT), and increased invasiveness through activation of the Notch pathway and matrix metalloproteinase MT1-MMP. Lastly, the data show that the changes in cell plasticity contributing to tumorigenic traits are not confined to virally induced cancers. Melanoma cell interaction with LECs leads to activation of the Notch pathway and increased adhesive, invasive, and metastatic properties of the tumor cells. In conclusion, the results show that regulation of cell plasticity through the Notch pathway takes place in different types of cancers, and it can affect several steps of tumorigenesis. A thorough and comprehensive understanding of the processes discovered herein may help develop better and more efficient treatments for these largely fatal malignancies.
  • Arovuori, Kyösti (Helsingin yliopisto, 2015)
    This dissertation analyses the effectiveness of the Common Agricultural Policy of the European Union. The motivation of this study arises from the fact that there is a lack of empirical research on the effects of policy instruments on the stated policy objectives. In addition, most of the analysis in the literature has focused on the policy objective to secure farmers incomes and, thus, on the efficiency of income redistribution. The policy effectiveness is defined as the ability of agricultural policy to respond to the stated policy objectives, given the general economic and structural conditions under which the policies operate. In this study, an empirical analysis of the effects of implemented policies and policy reforms on the stated policy objectives in the Common Agricultural Policy of the European Union is conducted. The analysis is carried out at the EU15 level and the time period analysed ranges from 1975 to 2007. In the empirical part, an econometric model utilising panel data for the EU15 countries is built. In the model, the development of the defined policy target variables is explained with policy variables and a set of economic and structural control variables. The results show that policy target variables have, in general, developed in the desired direction. The productivity of agriculture has increased, markets have been stable, self-sufficiency ratios have been achieved and the real term food prices have declined. However, farmers incomes have mostly declined. The implemented agricultural policy reforms have improved the policy effectiveness in general. The main contribution of the implemented reforms has been to the use of resources in agriculture. A policy shift from coupled price support to direct payments has released resources from agriculture to be utilised in other sectors. On the other hand, policy reforms have led to increasing price variation. This is a self-explanatory impact in the sense that administrative price setting was reduced and later on abolished in the policy reforms. According to this study, the impact of agricultural policy on the policy objectives is multifunctional. The implemented policy instruments may also have worked in the opposite direction compared to the targets set. While agricultural policies have clearly contributed to increasing agricultural productivity, they have also absorbed resources into the sector which could have been utilised more efficiently in other sectors. The country-level heterogeneity of economic and agricultural structures has increased especially due to the recent enlargements of the EU from EU15 to EU28. The analysis in this study shows that country-level heterogeneity has a significant impact on the development of policy target variables. Although the implemented policy reforms have made a contribution towards the desired direction and improved the effectiveness of the policies, it is a major challenge for future agricultural policies to effectively tackle the different structures.