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  • Soini, Eija (Helsingin yliopisto, 2006)
    This study aims at improving understanding of the interactions of livelihoods and the environment focusing on both socio-economic and biodiversity implications of land use change in the context of population pressure, global and local markets, climate change, cultural and regional historical factors in the highlands of East Africa. The study is based on three components (1) two extensive livelihood surveys, one on Mt. Kilimanjaro in Tanzania and the other in the Taita Hills of Kenya, (2) a land use change study of the southern slopes of Mt. Kilimanjaro focusing on land use trends between 1960s and 1980s and 1980s and 2000 and (3) a bird diversity study focusing on the potential impacts of the future land use change on birds in the main land use types on the slopes and the adjacent plains of Mt. Kilimanjaro. In addition, information on the highlands in Embu and the adjacent lowlands in Mbeere of Kenya are added to the discussion. Some general patterns of livelihood, land use and environment interactions can be found in the three sites. However, the linkages are very complex. Various external factors at different times in history have influenced most of the major turning points. Farmers continually make small adaptations to their farming practices, but the locally conceived alternatives are too few. Farmers lack specific information and knowledge on the most suitable crops, market opportunities and the quality requirements for growing the crops for markets. Population growth emerges as the most forceful driver of land use and environmental change. The higher altitudes have become extremely crowded with population densities in some areas higher than typical urban population densities. Natural vegetation has almost totally been replaced by farmland. Decreasing farm size due to population pressure is currently threatening the viability of whole farming systems. In addition, capital-poor intensification has lead to soil fertility depletion. Agricultural expansion to the agriculturally marginal lowlands has created a new and distinct group of farmers struggling constantly with climate variability causing frequent crop failures. Extensification to the fragile drylands is the major cause of fragmentation and loss of wildlife habitat. The linkages between livelihoods, land use and the environment generally point to degradation of the environment leading to reduced environmental services and ecosystem functions. There is no indication that the system is self-regulating in this respect. Positive interventions will be needed to maintain ecosystem integrity.
  • Mutanen, Annika (Helsingin yliopisto, 2014)
    Intestinal failure (IF) is characterized by the reduced capacity of the intestine to digest and absorb nutrients and fluids required for the maintenance of energy, fluid, electrolyte, and micronutrient balance, as well as normal growth and development in children. Patients with IF are at risk for multiple potentially life-threatening complications, including IF-associated liver disease (IFALD). In this thesis, studies on the incidence of long-term parenteral nutrition (PN) and IFALD, risk factors of IFALD, including parenteral plant sterols, and liver histology were performed to determine the long-term effects of pediatric onset IF on liver function and histology. During PN, serum plant sterol levels were significantly increased in neonates and children with IF compared to healthy controls. In neonates with IFALD, serum plant sterols ratios to cholesterol, especially stigmasterol, were increased compared with healthy controls, neonates without IFALD, and children on PN. After weaning off PN, IFALD, defined by liver biochemistry, persisted in 25% of neonates with 4.2- and 2.2-times higher serum stigmasterol and cholestanol ratios to cholesterol compared with neonates without IFALD. Abnormal liver histology was found in 94% of IF patients on PN and 77% of patients weaned off PN. During PN, liver histology was weighted with cholestasis and portal inflammation. After weaning off PN, cholestasis resolved, but significant fibrosis and steatosis persisted. Fibrosis stage was associated with remaining small bowel length, duration of PN, and number of septic episodes. In a multivariate analysis, age-adjusted small bowel length, portal inflammation, and absence of ileocaecal valve were predictive for fibrosis stage. Fibroblast growth factor 21 (FGF21), a hormone which is shown to regulate glucose and lipid metabolism and relate to liver steatosis in other conditions, concentration was markedly higher in IF patients with steatosis compared to those without steatosis. Liver steatosis was coupled with progression of fibrosis and reflected by serum FGF21. Based on our results, serum plant sterol levels are high and reflect their distribution in PN lipid emulsions during PN. In neonates, IFALD is frequent and associates with markedly increased serum plant sterols compared to healthy neonatal controls and children on PN with more mature liver function. After weaning off PN, serum stigmasterol and cholestanol remain high in neonates with persistent IFALD. Liver histology is characterized by cholestasis, portal inflammation, liver fibrosis and steatosis in IF patients on PN. After weaning off PN, portal inflammation diminishes and cholestasis resolves, but fibrosis and steatosis persists. In addition to duration of PN, extensive small intestinal resection and loss of ileocaecal valve as well as septic episodes are major risk factors of histological liver fibrosis. Increased serum FGF21 levels reflect the presence and the degree of liver steatosis in patients with pediatric onset IF.
  • Kotronen, Anna (Helsingin yliopisto, 2008)
    Introduction: The epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). However, not all obese subjects develop these metabolic abnormalities. Hepatic fat accumulation is related to hepatic insulin resistance, which in turn leads to hyperglycemia, hypertriglyceridemia, and a low HDL cholesterol con-centration. The present studies aimed to investigate 1) how intrahepatic as compared to intramyocellular fat is related to insulin resistance in these tissues and to the metabolic syndrome (Study I); 2) the amount of liver fat in subjects with and without the metabolic syndrome, and which clinically available markers best reflect liver fat content (Study II); 3) the effect of liver fat on insulin clearance (Study III); 4) whether type 2 diabetic patients have more liver fat than age-, gender-, and BMI-matched non-diabetic subjects (Study IV); 5) how type 2 diabetic patients using exceptionally high doses of insulin respond to addition of a PPARγ agonist (Study V). Subjects and methods: The study groups consisted of 45 (Study I), 271 (Study II), and 80 (Study III) non-diabetic subjects, and of 70 type 2 diabetic patients and 70 matched control subjects (Study IV). In Study V, a total of 14 poorly controlled type 2 diabetic patients treated with high doses of insulin were studied before and after rosiglitazone treatment (8 mg/day) for 8 months. In all studies, liver fat content was measured by proton magnetic resonance spectroscopy, and sub-cutaneous and intra-abdominal fat content by MRI. In addition, circulating markers of insulin resistance and serum liver enzyme concentrations were determined. Hepatic (i.v. insulin infusion rate 0.3 mU/kg∙min combined with [3-3H]glucose, Studies I, III, and V) and muscle (1.0 mU/kg min, Study I) insulin sensitivities were measured by the euglycemic hyperinsulinemic clamp technique. Results: Fat accumulation in the liver rather than in skeletal muscle was associated with features of insulin resistance, i.e. increased fasting serum (fS) triglycerides and decreased fS-HDL cholesterol, and with hyperinsulinemia and low adiponectin concentrations (Study I). Liver fat content was 4-fold higher in subjects with as compared to those without the metabolic syndrome, independent of age, gender, and BMI. FS-C-peptide was the best correlate of liver fat (Study II). Increased liver fat was associated with both impaired insulin clearance and hepatic insulin resistance independent of age, gender, and BMI (Study III). Type 2 diabetic patients had 80% more liver fat than age-, weight-, and gender-matched non-diabetic subjects. At any given liver fat content, S-ALT underestimated liver fat in the type 2 diabetic patients as compared to the non-diabetic subjects (Study IV). In Study V, hepatic insulin sensitivity increased and glycemic control improved significantly during rosiglitazone treatment. This was associated with lowering of liver fat (on the average by 46%) and insulin requirements (40%). Conclusions: Liver fat is increased both in the metabolic syndrome and type 2 diabetes independent of age, gender, and BMI. A fatty liver is associated with both hepatic insulin resistance and impaired insulin clearance. Rosi-glitazone may be particularly effective in type 2 diabetic patients who are poorly controlled despite using high insulin doses.
  • Brandt, Tatjana (Helsingin yliopisto, 2014)
    This article-based dissertation is an investigation of the early poetry of Agneta Enckell and Ann Jäderlund. The guiding hypothesis is that Enckell and Jäderlund enact and probe some of the central post-modern ideas about language and the subject dominating the intellectual context of the time. In particular, both poets are heavily influenced by Julia Kristeva s theories. The basic figure of thought functioning as a backdrop for their poetry is that we live in a male-dominated language, which determines our possibilities of expression. Hence, it becomes a crucial poetic task to resist the power of tradition and to carve out a free space in which new forms of personal female expression become possible. The five articles of the thesis investigate, through detailed close readings, how this constellation manifests itself in Enckell s and Jäderlund s poems. In the first article I read Jäderlund s poetry book Som en gång varit äng (1988) as centrally occupied with metapoetical issues that are played in a Narcissus scenario. The second article focuses on Jäderlund s poetry book Snart går jag i sommaren ut (1990). I employ Mikhail Bakhtin s theory of the carnival to shed light on Jäderlund s poetic effort to unsettle and transform traditional symbolic and linguistic structures. Moreover, I use of Kristeva s concept of the chora to elucidate Jäderlund s frequent use of words signifying empty spaces and hollow objects. The third article offers an analysis of the first three poetry books by Enckell: Förvandlingar mot morgonen (1983), rum; berättelser (1987), and Falla (Eurydike) (1991). Arguing that Enckell is guided by a vision of the emancipatory possibilities of poetry similar to that of Kristeva, I focus on Enckell s consistent use of spacings and caesuras in the text as signs of the privations of language that poetry hopes to articulate. The fourth article is an extended reading of Enckell s forth poetry book åter (1994). Here I employ Kristeva s theory of the abject to clarify the book s continuous effort to articulate experiences both appalling and sublime of the unsayable void, which simultaneously transcends and constitutes our language. The fifth article focuses on Jäderlund s first poetry book Vimpelstaden (1985). Drawing on Kristeva and Slavoj i ek, I analyze the disgust and horror that the I expresses in relation to language in general and especially in relation to its own voice.
  • Thomas, Ann-Sofie (2013)
    Syftet med detta arbete var att undersöka hurudan anknytning till föräldrarna och anpassning till samhället kvinnor som levt i barndomen under svåra omständigheter har. Kvinnorna som har intervjuats har blivit omhändertagna av socialväsendet när de var tonåringar eller annars har de aldrig blivit omhändertagna men varit klienter inom barnskyddet. Frågor som detta arbete kommer att försöka svara på är; Vem har dessa kvinnor kunnat lita på i sin barndom och hur har de knutit an till denna anknytningsfigur? Kan dessa kvinnor anpassa sig till samhället på ett ändamålsenligt sätt trots att de växt upp under svåra förhållanden? Undersökningen var en kvalitativ undersökning. Som datainsamlingsmetoder användes ”Adult attachment interview” och halvstrukturerad intervju. 5 kvinnor intervjuades. Analysmetoderna som användes var fallstudie och innehållsanalys och forskningsansatsen är fenomenologisk. Varje kvinnas fall är ett resultat. I analysen kom fram att kvinnan som aldrig omhändertogs och som ansåg sina föräldrar vara otrygga fullvuxna klarade sig bäst i samhället. Alla kvinnor hade anknytningsfigurer och hade slutfört grundskolan.
  • Joutsenniemi, Kaisla (Helsingin yliopisto, 2007)
    In line with major demographic changes in other Northern European and North American countries and Australia, being nonmarried is becoming increasingly common in Finland, and the proportion of cohabiters and of persons living alone has grown in recent decades. Official marital status no longer reflects an individual s living arrangement, as single, divorced and widowed persons may live alone, with a partner, with children, with parents, with siblings, or with unrelated persons. Thus, more than official marital status, living arrangements may be a stronger discriminator of one s social bonds and health. The general purpose of this study was to deepen our current understanding of the magnitude, trends, and determinants of ill health by living arrangements in the Finnish working-age population. Distinct measures of different dimensions of poor health, as well as an array of associated factors, provided a comprehensive picture of health differences by living arrangements and helped to assess the role of other factors in the interpretation of these differences . Mortality analyses were based on Finnish census records at the end of 1995 linked with cause-of-death registers for 1996 2000. The data included all persons aged 30 and over. Morbidity analyses were based on two comparable cross-sectional studies conducted twenty years apart (the Mini-Finland Survey in 1978 80 and the Health 2000 Survey in 2000 01). Both surveys were based on nationally representative samples of Finns aged 30 and over, and benefited from high participation rates. With the exception of mortality analyses, this study focused on health differences among the working-age population (mortality in age groups 30-64 and 65 and over, self-rated health and mental health in the age group 30-64, and unhealthy alcohol use in the age group 30-54). Compared with all nonmarried groups, married men and women exhibited the best health in terms of mortality, self-rated health, mental health and unhealthy alcohol use. Cohabiters did not differ from married persons in terms of self-rated health or mental health, but did exhibit excess unhealthy alcohol use and high mortality, particularly from alcohol-related causes. Compared with the married, persons living alone or with someone other than a partner exhibited elevated mortality as well as excess poor mental health and unhealthy alcohol use. By all measures of health, men and women living alone tended to be in the worst position. Over the past twenty years, SRH had improved least among single men and women and widowed women, and most among cohabiting women. The association between living arrangements and health has many possible explanations. The health-related selection theory suggests that healthy people are more likely to enter and maintain a marriage or a consensual union than those who are unhealthy (direct selection) or that a variety of health-damaging behavioural and social factors increase the likelihood of ill health and the probability of remaining without a partner or becoming separated from one s partner (indirect selection). According to the social causation theory, marriage or cohabitation has a health-promoting effect, whereas living alone or with others than a partner has a detrimental effect on health. In this study, the role of other factors that are mainly assumed to reflect selection, appeared to be rather modest. Social support, which reflects social causation, contributed only modestly to differences in unhealthy alcohol use by living arrangements, but had a larger effect on differences in poor mental health. Socioeconomic factors and health-related behaviour, which reflect both selection and causation, appeared to play a more important role in the excess poor health of cohabiters and of persons living alone or with someone other than a partner, than of married persons. Living arrangements were strongly connected to various dimensions of ill health. In particular, alcohol consumption appeared to be of great importance in the association between living arrangements and health. To the extent that the proportion of nonmarried persons continues to grow and their health does not improve at the same rate as that of married persons, the challenges that currently nonmarried persons pose to public health will likely increase.
  • Miranto, Mari (Helsingin yliopisto, 2006)
    In all plant conservation, the priority is to maintain wild populations in situ (on site), which means that plants are conserved within their natural environment. Sometimes, as in the case of severely endangered Saintpaulia H. Wendl. (African violets), this is however, no sufficient. In that case, ex situ (off site) conservation in the form of live and in vitro collections and seed banks is necessary. In recent years, the role of botanic gardens in conservation and reintroduction of threatened plants, has been increasingly recognized. Botanic gardens throughout the world possess large living collections of species and accessions, but only vague assumptions of the utility of them in ex situ conservation have been made thus far. Whole plants, when kept ex situ, have advantages in education, research and display. On the other hand, living collections have the disadvantage of high maintenance costs, including high spatial requirements. Thus, usually only one or few genotypes are represented. The goal of this study is to evaluate botanic garden live collections as a means of ex situ conservation with the genus Saintpaulia as a case study. As a result, an ex situ conservation plan for Saintpaulia is outlined. Workability of a network ex situ conservation activity in botanic gardens is also evaluated. Four of the five most important European Saintpaulia holders were chosen as target botanic gardens: Helsinki University Botanic Garden (Finland), The National Botanic Garden of Belgium, The Botanic Garden of Uppsala University (Sweden) and the Royal Botanic Gardens Edinburgh (UK). The wild Saintpaulia collections of the gardens were reviewed and the identifications checked. Botanic garden databases were examined to trace clone accessions. Leaf cuttings from wild-collected accessions were planted in Helsinki University Botanic Garden. Of the total 183 Saintpaulia accessions of the four target gardens 155 (85 %) were unique, and 126 of these were of known wild origin. They were chosen to ex situ conservation collection. Due to the varying quality of the data of origin of the accessions, five classes for the different quality of origin data were developed. European botanic garden living collections of Saintpaulia proved to be a workable base of ex situ conservation for the genus. The amount of space needed to conserve the ideal of at least 50 unique accessions of each of the 26 Saintpaulia taxa is best possible to organize with the network ex situ conservation programme: each accession will be stored in at least two botanic gardens, but no garden will have all the accessions. Saintpaulia is an ideal genus for living ex situ collections: it is beautiful and well-known, small-sized and easy to grow and propagate. New ex situ accessions will be collected from the wild and finally reintroduced to their natural habitats. Further research needs to be carried out to find out the proper seed banking mechanisms for probably orthodox but dust-like seeds of Saintpaulia species. The lack of research on the basic biology and the population ecology of the genus hampers effective conservation work. Collaboration with amenity horticulture and the home countries of Saintpaulia is planned to utilize the genetic diversity of wild African violets in breeding new cultivars.
  • Pimenoff, Ville (Helsingin yliopisto, 2008)
    The major aim of this thesis was to examine the origins and distribution of uniparental and autosomal genetic variation among the Finno-Ugric-speaking human populations living in Boreal and Arctic regions of North Eurasia. In more detail, I aimed to disentangle the underlying molecular and population genetic factors which have produced the patterns of uniparental and autosomal genetic diversity in these populations. Among Finno-Ugrics the genetic amalgamation and clinal distribution of West and East Eurasian gene pools were observed within uniparental markers. This admixture indicates that North Eurasia was colonized through Central Asia/ South Siberia by human groups already carrying both West and East Eurasian lineages. The complex combination of founder effects, gene flow and genetic drift underlying the genetic diversity of the Finno-Ugric- speaking populations were emphasized by low haplotype diversity within and among uniparental and biparental markers. A high prevalence of lactase persistence allele among the North Eurasian Finno- Ugric agriculturalist populations was also shown indicating a local adaptation to subsistence change with lactose rich diet. Moreover, the haplotype background of lactase persistence allele among the Finno- Ugric-speakers strongly suggested that the lactase persistence T-13910 mutation was introduced independently more than once to the North Eurasian gene pool. A significant difference in genetic diversity, haplotype structure and LD distribution within the cytochrome P450 CYP2C and CYP2D regions revealed the unique gene pool of the Finno-Ugric Saami created mainly by population genetic processes compared to other Europeans and sub-Saharan Mandenka population. From all studied populations the Saami showed also significantly the highest allele frequency of a CYP2C19 gene mutation causing variable drug reactions. The diversity patterns observed within CYP2C and CYP2D regions emphasize the strong effect of demographic history shaping genetic diversity and LD especially among such small and constant size populations as the Finno-Ugric-speaking Saami. Moreover, the increased LD in Saami due to genetic drift and/or admixture was shown to offer an advantage for further attempts to identify alleles associated to common complex pharmacogenetic traits.
  • Kontiainen, Pekka (Helsingin yliopisto, 2010)
    Individuals face variable environmental conditions during their life. This may be due to migration, dispersion, environmental changes or, for example, annual variation in weather conditions. Genetic adaptation to a novel environment happens through natural selection. Phenotypic plasticity allows, however, a quick individual response to a new environment. Phenotypic plasticity may also be beneficial for individual if the environment is highly variable. For example, eggs are costly to produce. If the food conditions vary significantly between breeding seasons it is useful to be able to adjust the clutch and egg size according to the food abundance. In this thesis I use Ural owl vole system to study phenotypic plasticity and natural selection using a number of reproduction related traits. The Ural owl (Strix uralensis) is a long-lived and sedentary species. The reproduction and survival of the Ural owl, in fact their whole life, is tied to the dramatically fluctuating vole densities. Ural owls do not cause vole cycles but they have to adjust their behaviour to the rather predictable population fluctuations of these small mammals. Earlier work with this system has shown that Ural owl laying date and clutch size are plastic in relation to vole abundance. Further, individual laying date clutch size reaction norms have been shown to vary in the amount of plasticity. My work extends the knowledge of natural selection and phenotypic plasticity in traits related to reproduction. I show that egg size, timing of the onset of incubation and nest defense aggressiveness are plastic traits with fitness consequences for the Ural owl. Although egg size is in general thought to be a fixed characteristic of an individual, this highly heritable trait in the Ural owl is also remarkably plastic in relation to the changes in vole numbers, Ural owls are laying the largest eggs when their prey is most abundant. Timing of the onset of incubation is an individual-specific property and plastic in relation to clutch size. Timing of incubation is an important underlying cause for asynchronous hatching in birds. Asynchronous hatching is beneficial to offspring survival in Ural owl. Hence, timing of the onset of incubation may also be under natural selection. Ural owl females also adjust their nest defense aggressiveness according to the vole dynamics, being most aggressive in years when they produce the largest broods. Individual females show different levels of nest defense aggressiveness. Aggressiveness is positively correlated with the phenotypic plasticity of aggressiveness. As elevated nest defense aggressiveness is selected for, it may promote the plasticity of aggressive nest defense behaviour. All the studied traits are repeatable or heritable on individual level, and their expression is either directly or indirectly sensitive to changes in vole numbers. My work considers a number of important fitness-related traits showing phenotypic plasticity in all of them. Further, in two chapters I show that there is individual variation in the amount of plasticity exhibited. These findings on plasticity in reproduction related traits suggest that variable environments indeed promote plasticity.
  • Kylliäinen, Janne (Helsingin yliopisto, 2009)
    How did Søren Kierkegaard (1813 1855) situate the human subject into historical and social actuality? How did he take into consideration his own situatedness? As key for understanding these questions the research takes the ideal of living poetically that Kierkegaard outlined in his dissertation. In The Concept of Irony (1841) Kierkegaard took up this ideal of the Romantic ironists and made it into an ethical-religious ideal. For him the ideal of living poetically came to mean 1) becoming brought up by God, while 2) assuming ethical-religiously one s role and place in the historical actuality. Through an exegesis of Kierkegaard s texts from 1843 to 1851 it is shown how this ideal governed Kierkegaard s thought and action throughout his work. The analysis of Kierkegaard s ideal of living poetically not only a) shows how the Kierkegaardian subject is situated in its historical context. It also b) sheds light on Kierkegaard s social and political thought, c) helps to understand Kierkegaard s character as a religious thinker, and d) pits his ethical-religious orientation in life against its scientific and commonsense alternatives. The research evaluates the rationality of the way of life championed by Kierkegaard by comparing it with ways of life dominated by reflection and reasoning. It uses Kierkegaard s ideal of living poetically in trying to understand the tensions between religious and unreligious ways of life.
  • Lindroos, Jenny (Helsingin yliopisto, 2015)
    Målet var att kartlägga livskvaliteten för att bedöma vårdeffektiviteten hos hemvårdspatienterna före och efter bytet av servicemodellen för medicinskt stöd inom Borgå stad. Studien undersökte ändamålsenligheten med HRQOL-instrumentet 15D och subjektiv hälsostatus för evaluering av livskvaliteten hos den i huvudsak geriatriska målgruppen. 499 hemvårdspatienter utgjorde kohorten som uppföljdes i 8 månader. Enkäten innehållande demografiska data, 15D, allmän hälsa mätt med första frågan ur SF-36 fylldes i av patienten själv eller med assistans av anhöriga eller vårdpersonalen. I första ronden svarade 347 och i andra ronden 268 personer. 15D-indexmedelvärdet var 0,7211 (SD 0,130) före interventionen och 0,7314 (SD 0,135) efter. Ökningen var inte statistiskt signifikant. Den allmänna hälsostatusen förbättrades väsentligt (p=0,037). Den nya servicemodellen konstaterades effektiv. Huruvida patienten besvarat enkäten ensam eller inte hade en självständig inverkan på 15D. Betydelsen av hjälp vid ifyllandet av livskvalitetsenkäten var större än förväntat och detta borde i större utsträckning beaktas vid dylika undersökningar.
  • Bärlund, Hanna Victoria (2013)
    Syftet med denna pro gradu-avhandling är att studera ungdomars övergångsskeden med tonvikt på arbetslösa ungdomars identitetsuppfattning. Inspiration för denna avhandling fick jag från ungdomsgarantins förberedande diskussion och den debatt kring ungdomsarbetslöshet som pågår. De centrala forskningsfrågorna är vad som kunde göras annorlunda för att undvika att de unga blir arbetslösa? Hurdana val gör de, vilka motgångar har de upplevt och vilka problem har de stött på vid olika övergångsskeden? Avhandlingens teoretiska utgångspunkt riktar sig mot risksamhället och de utmaningar som individualiseringen medfört ungdomar i dagens samhälle. Problematiken kring ungdomars övergångsskeden är mångfacetterad och bland annat valmöjligheterna vid utbildningsalternativen är idag oändliga. Materialet består av tio stycken narrativt uppbyggda intervjuer. Jag har intervjuat ungdomar som medverkar i ungdomsverkstadens Sveps verksamhet. Materialet samlade jag in i september och oktober månad under hösten 2012. Jag analyserade en del av materialet med den narrativa analysmetoden och en del med innehållsanalys. Jag valde att använda mig av båda analysmetoderna, eftersom både innehållet i berättelserna och berättarstrategierna intresserade mig. Därmed fick jag också ett bredare forskningresultat. Ungdomarna som medverkar i ungdomsverkstadsverksamheten kommer alla från olika omständigheter och har olika bakgrunder. Ett centralt forskningsresultat är att många ungdomar varit mobbade och känt utanförskap i grundskolan och detta har påverka ungdomarnas osäkerhetskänsla i livet. Särskilt vid övergångsskeden då det är frågan om att göra självständiga beslut har många varit osäkra om vad de vill eller kan. Många ungdomar som är på en ungdomsverkstad behöver också hjälp med att stärka den sociala kompetensen och bygga upp en uppfattning kring sin identitet. Resultatet av studien visar att ungdomarnas övergångsskeden har försvårats på grund av ovisshet kring möjligheterna och alternativen samt den egna förmågan att ta beslut och väga sina val.
  • Katajisto, Pekka (Helsingin yliopisto, 2008)
    Peutz-Jeghers syndrome (PJS) is a condition characterized by gastrointestinal polyposis and increased risk of cancer. At the onset of this study, mutations in the LKB1 serine/threonine kinase had been identified in approximately half of the studied PJS patients, indicating that LKB1 is a tumor suppressor underlying at least a subset of PJS cases. Mice with targeted heterozygous deletion of Lkb1 develop gastrointestinal polyps remarkably similar to PJS polyps corroborating the tumor suppressor function of LKB1/Lkb1. Most importantly, the polyps in Lkb1+/– mouse contain a notable stromal compartment with a core of smooth muscle cells that is the defining characteristic of a PJS polyp. In addition, the PJS and mouse polyps frequently exhibit elevated cyclooxygenase-2 (COX-2), a feature also noted in other gastrointestinal polyposis syndromes. Despite the aforementioned characterizations, the molecular mechanism driving PJS polyp development has not been identified. As only a subset of PJS patients have been reported to harbor LKB1 mutations, mutations in other loci might represent an alternative cause of PJS. To characterize the genetic background of PJS, mutation analysis of three genes encoding LKB1 interacting proteins, BRG1, STRADα, and MO25α, was performed in PJS patients without identified LKB1 mutations. No disease causing mutations were detected in these genes. The exclusion of the studied candidate genes with these criteria, and the concurrent increase in frequency of detected LKB1 mutations does not support involvement of other loci in PJS. As COX-2 inhibition has been effective in suppression of familial adenomatous polyposis, the elevation of COX-2 in PJS polyps suggested that COX-2 inhibition could decrease PJS polyposis. This was investigated by genetic and pharmacological interventions that targeted COX-2 in the Lkb1+/– mice. In comparison to PJS modeling Lkb1+/– mice, the polyp burden in the Lkb1+/– mice with either mono- or biallelic deletion of COX-2 was dramatically reduced. Furthermore, a selective COX-2 inhibitor celecoxib efficiently suppressed the tumor burden in Lkb1+/– mice. COX-2 inhibition reduced particularly the incidence of the large (>5mm) polyps whereas the number of smaller polyps was unaffected, suggesting that COX-2 expression is not required for polyp initiation but contributes significantly to tumor growth. These results prompted a pilot clinical trial with PJS patients receiving 200mg of celecoxib twice a day for 6 months. A subset of PJS patients (2/6) responded favorably to the celecoxib treatment, and a significant reduction in polyposis severity was also noted when the polyp grading data of all patients were combined. Together the data establish the polyposis promoting role of COX-2 in Peutz-Jeghers polyposis, and suggest that COX-2 inhibition is efficient in suppression of PJS polyposis. Polyp development is commonly thought to result from mutations in epithelial cells. However, the characteristic stroma of PJS polyps together with the suggestion that polyps can retain a functional copy of Lkb1 raised the possibility of non-epithelial origin of tumorigenesis in PJS. To investigate this possibility, murine Lkb1 was deleted tissue specifically in smooth muscle cells. Both monoallelic and biallelic deletions resulted in the development of gastrointestinal polyps indistinguishable from PJS polyps. Moreover, multiplicity of tumors in the smooth muscle specific biallelic deletion was only moderately (1.8-fold) higher than in the monoallelic deletion, demonstrating that Lkb1 LOH in stromal cells is not required for polyp development. The Lkb1 deficient mesenchymal cells produced less TGFß, and p-Smad2 staining was reduced in epithelial cells adjacent to Lkb1 deleted mesenchyme. These results identified impaired TGFß signaling from mesenchyme to epithelium as a possible mechanism for polyp development. Consistently, the epithelial proliferation in tumors coincided with the reduced p-Smad2 staining and with Lkb1 deficiency of the adjacent stroma. The TGFß signaling defect was importantly also noted in polyps from PJS patients, supporting the role of stroma as a major contributor to PJS polyposis by generation of a permissive microenvironment for epithelial expansion. The results of this thesis contribute to the notion that LKB1 is the only PJS gene substantiating the findings from the Lkb1 heterozygous mouse model of PJS. From the viewpoint of therapy development, the results provide proof of principle for the efficacy of COX-2 chemoprevention in PJS. Furthermore, the discovery of the stromal-derived mechanism of LKB1 tumor suppression forms a basis for the development of novel therapeutic interventions targeting mesenchymal signaling in PJS polyposis and possibly other cancers with loss of LKB1.
  • Vuori, Arto (Helsingin yliopisto, 2009)
    Low Level Virtual Machine (LLVM) on moderni koko ohjelman elinkaaren optimointeihin keskittyvä kääntäjäarkkitehtuuri. Java-virtuaalikone on puolestaan suosittu korkean tason virtuaalikone, johon monien ohjelmointikielten toteutus nykyään perustuu. Tutkielmassa esitellään alun perin suorituskykyisen C- ja C++-kääntäjän toteuttamiseksi luotu LLVM-järjestelmä ja arvioidaan, miten hyvin LLVM-infrastruktuuri tukee Java-virtuaalikoneen toteuttamista. Tämän lisäksi tutkielmassa pohditaan, miten dynaamisten kielten usein tarvitsemaa suoritusaikaista ja lähdekieliriippuvaista optimointia voidaan tukea lähdekieliriippumattomassa LLVM-järjestelmässä. Lopuksi tutkielmassa esitellään kehitysehdotelma yleisen roskienkeruuinfrastruktuurin toteuttamiseksi LLVM:ssä, mikä tukisi dynaamista muistia automaattisesti hallitsevien kielten, kuten Javan ja sen virtuaalikoneen toteuttamista.
  • Holm, Jenny (Helsingfors universitet, 2013)
    Listeria monocytogenes on elintarvikevälitteinen, opportunistinen patogeeni, joka voi aiheuttaa ihmiselle listerioosin. Kannat sietävät hyvin jääkaappilämpötiloja ja sopeutuvat erilaisiin elinympäristöihin. Elintarvikelaitoksissa listeriat ovat usein pysyviä laitoskantoja, jotka kontaminoivat tuotteita usein pitkällä aikavälillä. Tämän maisterin tutkielman laboratorio-osuus tehtiin syyslukukauden 2012 aikana Eläinlääketieteellisen tiedekunnan elintarvikehygienian ja ympäristöterveyden osastolla, mikrobiologisen elintarviketurvallisuuden huippuyksikössä. Tarkoituksena oli tutkia DEAD-Box RNA helikaasien vaikutusta L. monocytogenes EGD-e –kannan flagellan ilmenemiseen ja kiinnittymiseen. Kirjallisuuden mukaan L. monocytogenes –kantojen kiinnittymiseen vaikuttavat suuresti mahdollisesti adhesiivisina toimivien flagellojen läsnäolo sekä solujen liikkuvuus. L. monocytogenes EGD-e–kannalla on neljä DEAD-Box RNA helikaasigeeniä (lmo0866, lmo1246, lmo1450 ja lmo1722), joista osa vaikuttaa kasvuun ja liikkuvuuteen. Kaksi geeneistä vaikuttaa lisäksi positiivisesti bakteerin selviämiseen kylmän, etanolin ja emäksisen tai hapettavan kasvuympäristön aiheuttamassa stressitilanteessa. L. monocytogenes EGD-e mutanttikannoista ?lmo0866 ja ?lmo1450 on todettu liikkumattomiksi ja ?lmo1722 osittain liikkuvaksi. Nämä mutanttikannat ovat lisäksi kylmänherkkiä DEAD-Box RNA helikaasimutanttikannat ja villityyppi kuvattiin TEM-tekniikalla ja kahden flagellageenin (flhA ja motA) ilmentymistä mitattiin qRT-PCR:lla. Lopuksi kantojen kiinnittymistä tutkittiin mikrotiitterilevymenetelmällä. Kaikki tutkimukset tehtiin kahdessa lämpötilassa (+25 ja +37°C:ssa). Elektronimikroskooppikuvat ja qRT-PCR –tulokset olivat toisiaan tukevia. Mutanttikanta ?lmo0866 ei tuottanut flagelloja lainkaan, kun taas kannalla ?lmo1450 flagellojen tuotto oli heikompaa villityyppiin verrattuna +25°C:ssa. Kannat ?lmo1246 ja ?lmo1722 vastasivat villityyppiä flagellan esiintymisen suhteen. Mutanttikannoista ?lmo0866 ilmensi +25°C:ssa molempia tutkittuja flagellageenejä yli 20-kertaa vähemmän kuin villityyppi. Myös geenin lmo1450 poistaminen johti flagellageenien ilmentymisen vähenemiseen. Mutanttikannan ?lmo1722 osalta ilmentyminen oli alentunut vain toisen tutkitun flagellageenin (motA) osalta. Geenin lmo1246 deleetio ei vaikuttanut flagellageenien ilmentymiseen. Kiinnittymisessä eroja ei havaittu helikaasimutanttien ja villityypin välillä kummassakaan tutkitussa lämpötilassa, joten yksittäiset DEAD-Box RNA helikaasigeenit eivät vaikuta L. monocytogenes EGD-e –kannan kiinnittymiseen. L. monocytogenes –bakteerin kiinnittymiseen polystyreenipinnalle vaikuttavat kirjallisuuden mukaan useat eri tekijät, kuten inkubointilämpötila, -aika, ravinteet ja kanta. Flagellan ja liikkuvuuden merkitys kiinnittymiseen ei ole mahdollisesti niin suuri kuin on aiemmin oletettu.