Cholesterol Disturbances in Inherited Neurodegenerative Diseases : Studies on Npc1, Ppt1 and Ctsd deficient mice

The central nervous system (CNS) is the most cholesterol-rich organ in the body. Cholesterol is essential to CNS functions such as synaptogenesis and formation of myelin. Significant differences exist in cholesterol metabolism between the CNS and the peripheral organs. However, the regulation of cholesterol metabolism in the CNS is poorly understood compared to our knowledge of the regulation of cholesterol homeostasis in organs reached by cholesterol-carrying lipoprotein particles in the circulation. Defects in CNS cholesterol homeostasis have been linked to a variety of neurodegenerative diseases, including common diseases with complex pathogenetic mechanisms such as Alzheimer s disease. In spite of intense effort, the mechanisms which link disturbed cholesterol homeostasis to these diseases remain elusive. We used three inherited recessive neurodegenerative disorders as models in the studies included in this thesis: Niemann-Pick type C (NPC), infantile neuronal ceroid lipofuscinosis and cathepsin D deficiency. Of these three, NPC has previously been linked to disturbed intracellular cholesterol metabolism. Elucidating the mechanisms with which disturbances of cholesterol homeostasis link to neurodegeneration in recessive inherited disorders with known genetic lesions should shed light on how cholesterol is handled in the healthy CNS and help to understand how these and more complex diseases develop. In the first study we analyzed the synthesis of sterols and the assembly and secretion of lipoprotein particles in Npc1 deficient primary astrocytes. We found that both wild type and Npc1 deficient astrocytes retain significant amounts of desmosterol and other cholesterol precursor sterols as membrane constituents. No difference was observed in the synthesis of sterols and the secretion of newly synthesized sterols between Npc1 wild type, heterozygote or knockout astrocytes. We found that the incorporation of newly synthesized sterols into secreted lipoprotein particles was not inhibited by Npc1 mutation, and the lipoprotein particles were similar to those excreted by wild type astrocytes in shape and size. The bulk of cholesterol was found to be secreted independently of secreted NPC2. These observations demonstrate the ability of Npc1 deficient astrocytes to handle de novo sterols, and highlight the unique sterol composition in the developing brain. Infantile neuronal ceroid lipofuscinosis is caused by the deficiency of a functional Ppt1 enzyme in the cells. In the second study, global gene expression studies of approximately 14000 mouse genes showed significant changes in the expression of 135 genes in Ppt1 deficient neurons compared to wild type. Several genes encoding for enzymes of the mevalonate pathway of cholesterol biosynthesis showed increased expression. As predicted by the expression data, sterol biosynthesis was found to be upregulated in the knockout neurons. These data link Ppt1 deficiency to disturbed cholesterol metabolism in CNS neurons. In the third study we investigated the effect of cathepsin D deficiency on the structure of myelin and lipid homeostasis in the brain. Our proteomics data, immunohistochemistry and western blotting data showed altered levels of the myelin protein components myelin basic protein, proteolipid protein and 2 , 3 -cyclic nucleotide 3 phosphodiesterase in the brains of cathepsin D deficient mice. Electron microscopy revealed altered myelin structure in cathepsin D deficient brains. Additionally, plasmalogen-derived alkenyl chains and 20- and 24-carbon saturated and monounsaturated fatty acids typical for glycosphingolipids were found to be significantly reduced, but polyunsaturated species were significantly increased in the knockout brains, pointing to a decrease in white matter. The levels of ApoE and ABCA1 proteins linked to cholesterol efflux in the CNS were found to be altered in the brains of cathepsin D deficient mice, along with an accumulation of cholesteryl esters and a decrease in triglycerols. Together these data demonstrate altered myelin architecture in cathepsin D deficient mice and link cathepsin D deficiency to aberrant cholesterol metabolism and trafficking. Basic research into rare monogenic diseases sheds light on the underlying biological processes which are perturbed in these conditions and contributes to our understanding of the physiological function of healthy cells. Eventually, understanding gained from the study of disease models may contribute towards establishing treatment for these disorders and further our understanding of the pathogenesis of other, more complex and common diseases.

Hintakäsitykset funktionaalisista elintarvikkeista ja euron käyttöönoton vaikutus

Työn tavoitteena oli tutkia kuluttajien hintakäsityksiä funktionaalisista elintarvikkeista sekä euron käyttöönoton vaikutuksia niihin. Teoriaosassa tarkasteltiin funktionaalisen elintarvikkeen käsitettä ja sen hintaan liittyviä kysymyksiä erikoistuotteen näkökulmasta sekä kuluttajan hintakäsityksen muodostumisessa tärkeää osaa näyttelevää referenssihintaa ja sen vaikutuksia sekä teoreettista taustaa, erityisesti adaptaatiotasoteoriaa. Lisäksi tarkasteltiin euron mahdollisia vaikutuksia referenssihintaan sekä referenssihinnan roolia kuluttajan hintakäsityksen muodostumisessa. Työn empiirinen osa koostui kahdesta kyselytutkimuksesta, jotka suoritettiin ennen euron käyttöönottoa joulukuussa 2001 ja sen jälkeen huhtikuussa 2002. Ensimmäiseen kyselyyn vastasi 182 ja toiseen 135 vastaajaa. Vastaajat olivat pääkaupunki- sekä Hämeenlinnan seudulta. Tutkimuksen kohteena olevat tuotteet olivat Gefilus®-piimä ja -mehut, ja kohderyhmänä niiden käyttäjät. Tutkimuksen empiirisessä osassa selvitettiin funktionaalisten elintarvikkeiden käyttö- ja ostotottumuksia sekä mielipidettä niiden hintatasosta suhteessa terveysvaikutuksiin ja tavallisiin elintarvikkeisiin. Referenssihintoja tutkimuksen kohteena oleville tuotteille tutkittiin sopivana, korkeimpana ja alhaisimpana hyväksyttävänä hintana.Euron vaikutuksia hintakäsityksiin tutkittiin vastausten eroissa kyselyjen välillä. Euron käyttöönoton aiheuttamia referenssihintojen muutoksia tarkasteltiin hintaherkkyysmittari avulla. Lisäksi tutkittiin euron käyttöönoton aiheuttamia muutoksia ostokäyttäytymisessä. Faktori- ja ryhmittelyanalyyseja käytettiin vastaajien ryhmittelyyn. Funktionaalisia elintarvikkeita pidettiin vastaajien joukossa kalliina suhteessa niiden terveysvaikutuksiin tai tavallisten, ei-funktionaalisten, tuotteiden hintaan. Tutkimuksen kohteena olleiden tuotteiden, Gefilus®-piimän ja -mehujen, hintatasoa pidettiin myös kalliina. Gefilus®-mehujen hintaa pidettiin yleisesti liian kalliina. Euron käyttöönotto aiheutti muutoksia vastaajien referenssihinnoissa. Euron käyttöönoton voitiin havaita vaikuttaneen kuluttajien hintakäsityksiin siten, että hinnat vaikuttivat aikaisempaa halvemmilta. Lisäksi euron käyttöönotto oli vaikeuttanut hintojen arviointia. Lähes kaikki vastaajat olivat sitä mieltä, että euron käyttöönoton jälkeen hinnat olivat nouseet. Euron käyttöönotto oli myös lisännyt pankkikortin käyttöä maksuvälineenä käteisen sijaan. Avainsanat: funktionaalinen elintarvike, terveysvaikutteinen elintarvike, hintakäsitys, referenssihinta, euro

The Nature, Origins, and Consequences of Finnish Shame-Proneness: A Grounded Theory Study

Although shame is a universal human emotion and is one of the most difficult emotions to overcome, its origins and nature as well as its effects on psychosocial functioning are not well understood or defined. While psychological and spiritual counselors are aware of the effects and consequences of shame for an individual s internal well-being and social life, shame is often still considered a taboo topic and is not given adequate attention. This study aims to explain the developmental process and effects of shame and shame-proneness for individuals and provide tools for practitioners to work more effectively with their clients who struggle with shame. This study presents the empirical foundation for a grounded theory that describes and explains the nature, origins, and consequences of shame-proneness. The study focused on Finnish participants childhood, adolescence and adulthood experiences and why they developed shame-proneness, what it meant for them as children and adolescents and what it meant for them as adults. The data collection phase of this study began in 2000. The participants were recruited through advertisements in local and country-wide newspapers and magazines. Altogether 325 people responded to the advertisements by sending an essay concerning their shame and guilt experiences. For the present study, 135 essays were selected and from those who sent an essay 19 were selected for in-depth interviews. In addition to essays and interviews, participants personal notebooks and childhood hospital and medical reports as well as their scores on the Internalized Shame Scale were analyzed. The development of shame-proneness and significant experiences and events during childhood and adolescence (e.g., health, parenting and parents behavior, humiliation, bullying, neglect, maltreatment and abuse) are discussed and the connections of shame-proneness to psychological concepts such as self-esteem, attachment, perfectionism, narcissism, submissiveness, pleasing others, heightened interpersonal subjectivity, and codependence are explained. Relationships and effects of shame-proneness on guilt, spirituality, temperament, coping strategies, defenses, personality formation and psychological health are also explicated. In addition, shame expressions and the development of shame triggers as well as internalized and externalized shame are clarified. These connections and developments are represented by the core category lack of gaining love, validation and protection as the authentic self. The conclusions drawn from the study include a categorization of shame-prone Finnish people according to their childhood and adolescent experiences and the characteristics of their shame-proneness and personality. Implications for psychological and spiritual counseling are also discussed. Key words: shame, internalized shame, external shame, shame development, shame triggers, guilt, self-esteem, attachment, narcissism, perfectionism, submissiveness, codependence, childhood neglect, childhood abuse, childhood maltreatment, emotional abuse, sexual abuse, spiritual abuse, psychological well-being

Future chemistry teachers use of knowledge dimensions and high-order cognitive skills in pre-laboratory concept maps

This poster describes a pilot case study, which aim is to study how future chemistry teachers use knowledge dimensions and high-order cognitive skills (HOCS) in their pre-laboratory concept maps to support chemistry laboratory work. The research data consisted of 168 pre-laboratory concept maps that 29 students constructed as a part of their chemistry laboratory studies. Concept maps were analyzed by using a theory based content analysis through Anderson & Krathwohls' learning taxonomy (2001). This study implicates that novice concept mapper students use all knowledge dimensions and applying, analyzing and evaluating HOCS to support the pre-laboratory work.

Juvenile diversity of tree species in Theobroma cacao L. agroforestry and primary forest – Central Sulawesi, Indonesia

This thesis studies the tree species’ juvenile diversity in cacao (Theobroma cacao L.) based agroforestry and in primary forest in a natural conservation forest environment of Lore Lindu National Park, Sulawesi, Indonesia. Species’ adult composition in Lore Lindu National Park is relatively well studied, less is known about tree species’ diversity in seedling communities particularly in frequently disturbed cacao agroforestry field environment. Cacao production forms a potentially serious thread for maintaining the conservation areas pristine and forested in Sulawesi. The impacts of cacao production on natural environment are directly linked to the diversity and abundance of shade tree usage. The study aims at comparing differences between cacao agroforestry and natural forest in the surrounding area in their species composition in seedling and sapling size categories. The study was carried out in two parts. Biodiversity inventory of seedlings and saplings was combined with social survey with farmer interviews. Aim of the survey was to gain knowledge of the cacao fields, and farmers’ observations and choices regarding tree species associated with cacao. Data was collected in summer 2008. The assessment of the impact of environmental factors of solar radiation, weeding frequency, cacao tree planting density, distance to forest and distance to main park road, and type of habitat on seedling and sapling compositions was done with Non-metric Multidimensional Scaling (NMS). Outlier analysis was used to assess distorting variables for NMS, and Multi-Response Permutation Procedures (MRPP) analysis to differentiate the impact of categorical variables. Sampling success was estimated with rarefaction curves and jackknife estimate of species richness. In the inventory 135 species of trees and shrubs were found. Only some agroforestry related species were dominating. The most species rich were sapling communities in forest habitat. NMS was showing generally low linear correlation between variation of species composition and environmental variables. Solar radiation was having most significance as explaining variable. The most clearly separated in ordination were cacao and forest habitats. The results of seedling and sapling inventory were only partly coinciding with farmers’ knowledge of the tree species occurring on their fields. More research with frequent assessment of seedling cohorts is needed due to natural variability of cohorts and high mortality rate of seedlings.

Knowledge Transfer within Western Multinationals' Subsidiary Units in China and Finland - The Impact of Headquarter Control Mechanisms, Subsidiary Location and Social Capital (summary section only)

It is suggested that the ability and practices of how the multinational corporation (MNC) manages knowledge transfer among its geographically dispersed subsidiary units are crucial for the building and development of firm competitive advantage. However, cross-border transfer of valuable organizational knowledge is likely to be problematic and laborious, especially within diversified and differentiated MNCs. Using data collected from 164 western multinational companies’ subsidiary units located in China and Finland, this study aims to investigate cross-border knowledge transfer within the MNC. It explores a number of factors that influence the transfer of knowledge among units in the differentiated MNC. The study consists of five individual papers. Paper 1 investigates a range of organizational mechanisms that may positively influence a subsidiary’s propensity to undertake knowledge transfers to other parts of the corporation. Paper 2 explores the impact of subsidiary location on the motivational dispositions of knowledge receiving units to value and accept knowledge from subsidiaries located in economically less advanced countries. Paper 3 examines the influence of social capital variables on knowledge transfer in dyadic relationships between foreign-owned subsidiaries and their sister and patent units. Paper 4 provides some initial insights into potentially different effects of trust and shared vision in intra-organizational vs. inter-organizational relationships. Using a case study setting, Paper 5 explores means and mechanisms used in transferring human resource management practices to Western MNCs’ business units in China from a cultural perspective. The results of the study show that MNC management through choices regarding organizational controls can encourage and enhance corporate-internal knowledge transfer. It also finds evidence that more knowledge is transferred from subsidiaries located in an industrialized country (e.g., Finland) than subsidiaries located in a developing country (e.g., China). While the study has highlighted the importance of social capital in promoting knowledge transfer, it has also uncovered some new findings that the effect of trust and shared vision may be contingent upon different contexts. Finally, in Paper 5, a number of mechanisms used in transferring selected HRM practices and competences to the Chinese business units have been identified. The findings suggest that cultural differences should be taken into consideration in the choice and use of different transfer mechanisms.

Bank Run Risk and Optimal Reserves

We characterize the optimal reserves, and the generated probability of a bank run, as a function of the penalty imposed by the central bank, the probability of depositors’ liquidity needs, and the return on outside investment opportunities.

Corporate Brand Repositioning with CSR as the Differentiating Factor: A Study on Consumer Perceptions

Purpose – This research paper studies how the strategy of repositioning enables marketers to communicate CSR as their brand’s differentiating factor. It aims at understanding how consumer perceptions can be managed to generate brand value through corporate brand repositioning when CSR is the differentiating factor. The purpose of this paper is to answer the following research question: How can consumer perceptions be managed to generate brand value through corporate brand repositioning when CSR is the differentiating factor? The two research objectives were: 1. to build a model, which describes the different components of consumer perceptions involved in generation of brand value through repositioning when CSR is the differentiating factor, 2. to identify the most critical components in the context of the case company, IKEA for generation of brand value during the process of corporate brand repositioning Design/methodology/approach – This paper is based on the literature review covering the logic of brand value generation, repositioning strategy and consumer perceptions connected to CSR activities. A key concept of the positioning theory, the brand’s differentiating factor, was explored. Previous studies have concluded that desirability of the differentiating factor largely determines the level of brand value-creation for the target customers. The criterion of desirability is based on three dimensions: relevance, distinctiveness and believability. A model was built in terms of these desirability dimensions. This paper takes a case study approach where the predefined theoretical framework is tested using IKEA as the case company. When developing insights on the multifaceted nature of brand perceptions, personal interviews and individual probing are vital. They enable the interviewees to reflect on their feelings and perceptions with their own words. This is why the data collection was based on means-end type of questioning. Qualitative interviews were conducted with 12 consumers. Findings – The paper highlights five critical components that may determine whether IKEA will fail in its repositioning efforts. The majority of the critical components involved believability perceptions. Hence, according to the findings, establishing credibility and trustworthiness for the brand in the context of CSR seems primary. The most critical components identified of the believability aspect were: providing proof of responsible codes of conduct via conducting specific and concrete CSR actions, connecting the company’s products and the social cause, and building a linkage between the initial and new positioning while also weakening the old positioning. Originality/value – Marketers’ obligation is to prepare the company for future demands. Companies all over the globe have recognized the durable trend of responsibility and sustainability. Consumer´s worry about the environmental and social impact of modern lifestyles is growing. This is why Corporate Social Responsibility (CSR) provides brands an important source of differentiation and strength in the future. The strategy of repositioning enables marketers to communicate CSR as their brand’s differentiating factor. This study aimed at understanding how consumer perceptions can be managed to generate brand value through corporate brand repositioning when CSR is the differentiating factor.

Museo yhteiskunnan peilinä? - pääkaupunkiseudulle perustetut kulttuurihistorialliset museot 1875-2010

Tässä pro gradu –tutkielmassa tarkastellaan museoita osana yhteiskunnan historiakulttuuria; niitä tapoja joiden pohjalta käsityksiä menneestä tuotetaan ja käytetään. Aihetta lähestytään kysymällä millaisia kulttuurihistoriallisia museoita pääkaupunkiseudulle on perustettu ja millaiset teemat eivät ole olleet museon arvoisia. Tutkielmassa selvitetään onko pääkaupunkiseudulle perustetuissa kulttuurihistoriallisissa museoissa havaittavissa ajallista aaltoa sen suhteen millaisille aiheille on perustettu oma museo. Lopuksi pohditaan esimerkkitapausten valossa sitä, miten erilaisia teemoja edustavien museoiden perustamistarvetta on perusteltu omana aikanaan. Etsimällä vastauksia tutkimuskysymyksiin pyritään samalla hahmotetaan sitä, millaista yhteiskunnallista historiakulttuuria museot ovat olleet osa. Työn ensimmäisessä vaiheessa kartoitettiin millaisia kulttuurihistoriallisia museoita pääkaupunkiseudulla on ollut. Museoviraston ja Suomen museoliiton aineistojen avulla on listattu kooste vuosien 1875-2010 välillä pääkaupunkiseudulla olleista museoista. Museoiden perustamiseen ja museokentältä katoamiseen liittyvää koostetta on täydennetty Helsingin matkailuyhdistyksen julkaisujen tiedoilla sekä museoiden omilla tiedonannoilla. Tutkielman museot on luokiteltu edustamiensa teemojen mukaan. Tarkoituksena on ollut hahmotella miten pääkaupunkiseudun kulttuurihistoriallisten museoiden kenttä on muuttunut 135 vuoden aikana. Työn toisessa vaiheessa tarkasteltiin neljän esimerkkitapauksen kautta museokentän ajallista muutosta ja sitä millaisia perusteluita museoiden perustamiselle on annettu sekä millaista keskustelua museon perustamisesta on omana aikanaan käyty. Esimerkkitapausten tarkastelun lähteinä käytettiin arkistomateriaalia, aikakauden lehdissä museoista käytyä keskustelua ja museoista kirjoitettuja historiikkeja. Pääkaupunkiseudun kulttuurihistoriallisissa museoissa on tutkielman mukaan havaittavissa löyhä ajallinen muutos. Kulttuurihistoriallisten museoiden edustamat historian kertomukset ovat muuttuneet ja pirstaloituneet 135 vuoden aikana virallisesta, kansallisesta historian kertomuksesta kohti useita pienempiä historian kertomuksia ja erilaisten ryhmien omaa historiaa. 1800-1900-lukujen taitteessa perustettiin pääosin valtiollisia ja instituutioiden historiaan keskittyneitä museoita sekä suurmiehille omistettuja henkilöhistoriallisia museoita. Valtiolliset ja henkilöhistorialliset teemat näkyvät museoissa läpi koko tutkielman tarkasteluajanjakson. Kansallisen historian katse suuntasi paikalliseen 1900-luvun alussa ja 1980-luvulla, jolloin perustettiin erityisen paljon paikallishistoriallisia ja alueellisia museoita. 1970-1990-luvuilla museokenttää hallitsivat monet tekniikkaan, teollisuuteen ja yrityshistoriaan keskittyneet museot. Tultaessa 2000-luvulle museot edustivat lapsiin, nuoriin, koulutukseen ja monikulttuurisuuteen liittyviä teemoja. Tutkielman toisen vaiheen esimerkkitapausten tarkastelu osoitti, että erilaisia teemoja edustavien museoiden perustamistarvetta perustellaan hyvin samankaltaisesti. Niin 1800-luvun lopussa kuin 1900-luvun lopussa museoiden tarvetta perusteltiin kasvatus- ja sivistystyöllä ja aihealueen arvostuksen kasvulla. Museon perustamisen koettiin osoittavan Suomen kuuluvan osaksi länsimaisia sivistysyhteiskuntia. Museoiden perustamisen taustalla on usein ollut asiaa ajanut yhdistys. Kuitenkin museohanke on ollut vuosikausien projekti ja konkretisoitunut usein vasta kun museon tiloihin ja talouteen liittyvät kysymykset on saatu kuntoon. Tutkielman loppupäätelmien myötä hahmottui monia historiantutkimuksellisen lisätarkastelun arvoisia aiheita museoista osana yhteiskunnan historiakulttuuria. Avainsanat – Nyckelord – Keywords kulttuurihistorialliset museot, historiakulttuuri, historiankäyttö, yhteiskunta