Functional role of the Mso1p-Sec1p complex in membrane fusion regulation

Sec1/Munc18 (SM) protein family members are evolutionary conserved proteins. They perform an essential, albeit poorly understood function in SNARE complex formation in membrane fusion. In addition to the SNARE complex components, only a few SM protein binding proteins are known. Typically, their binding modes to SM proteins and their contribution to the membrane fusion regulation is poorly characterised. We identified Mso1p as a novel Sec1p interacting partner. It was shown that Mso1p and Sec1p interact at sites of polarised secretion and that this localisation is dependent on the Rab GTPase Sec4p and its GEF Sec2p. Using targeted mutagenesis and N- and C-terminal deletants, it was discovered that the interaction between an N-terminal peptide of Mso1p and the putative Syntaxin N-peptide binding area in Sec1p domain 1 is important for membrane fusion regulation. The yeast Syntaxin homologues Sso1p and Sso2p lack the N-terminal peptide. Our results show that in addition to binding to the putative N-peptide binding area in Sec1p, Mso1p can interact with Sso1p and Sso2p. This result suggests that Mso1p can mimic the N-peptide binding to facilitate membrane fusion. In addition to Mso1p, a novel role in membrane fusion regulation was revealed for the Sec1p C-terminal tail, which is missing in its mammalian homologues. Deletion of the Sec1p-tail results in temperature sensitive growth and reduced sporulation. Using in vivo and in vitro experiments, it was shown that the Sec1p-tail mediates SNARE complex binding and assembly. These results propose a regulatory role for the Sec1p-tail in SNARE complex formation. Furthermore, two novel interaction partners for Mso1p, the Rab GTPase Sec4p and plasma membrane phospholipids, were identified. The Sec4p link was identified using Bimolecular Fluorescence Complementation assays with Mso1p and the non-SNARE binding Sec1p(1-657). The assay revealed that Mso1p can target Sec1p(1-657) to sites of secretion. This effect is mediated via the Mso1p C-terminus, which previously has been genetically linked to Sec4p. These results and in vitro binding experiments suggest that Mso1p acts in cooperation with the GTP-bound form of Sec4p on vesicle-like structures prior to membrane fusion. Mso1p shares homology with the PIP2 binding domain of the mammalian Munc18 binding Mint proteins. It was shown both in vivo and in vitro that Mso1p is a phospholipid inserting protein and that this insertion is mediated by the conserved Mso1p amino terminus. In vivo, the Mso1p phospholipid binding is needed for sporulation and Mso1p-Sec1p localisation at the sites of secretion at the plasma membrane. The results reveal a novel layer of membrane fusion regulation in exocytosis and propose a coordinating role for Mso1p in connection with membrane lipids, Sec1p, Sec4p and SNARE complexes in this process.

Functional regulation of the Neurofibromatosis 2 tumor suppressor merlin

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder manifested by the formation of multiple benign tumors of the nervous system. Affected individuals typically develop bilateral vestibular schwannomas which lead to deafness and balance disorders. The syndrome is caused by inactivation of the NF2 tumor suppressor gene, and mutation or loss of the NF2 product, merlin, is sufficient for tumorigenesis in both hereditary and sporadic NF2-associated tumors. Merlin belongs to the band 4.1 superfamily of cytoskeletal proteins, which also contain the related ezrin, radixin, and moesin (ERM) proteins. The ERM members provide a link between the cell cytoskeleton and membrane by connecting membrane-associated proteins to actin filaments. By stabilizing complexes in the cell cortex, the ERMs modulate morphology, growth, and migration of cells. Despite their structural homology, overlapping subcellular distribution, direct molecular association, and partial overlap of molecular interactions, merlin and ezrin exert opposite effects on cell proliferation. Merlin suppresses cell proliferation, whereas ezrin expression is linked to oncogenic activity. We hypothesized that the regions which differ between the proteins might explain merlin s specificity as a tumor suppressor. We therefore analyzed the regions, which are most diverse between merlin and ezrin; the N-terminal tail and the C-terminus. To determine the properties of the C-terminal region, we studied the two most predominant merlin isoforms together with truncation variants similar to those found in patients. We also focused on the evolutionally conserved C-terminal residues, E545-E547, that harbor disease causing mutations in its corresponding DNA sequence. In addition to inhibiting cell proliferation, merlin regulates cytoskeletal organization. The morphogenic properties of merlin may play a role in tumor suppression, since patient-derived tumor cells demonstrate cytoskeletal abnormalities. We analyzed the mechanisms of merlin-induced extension formation and determined that the C-terminal region of amino acids 538-568 is particularly important for the morphogenic activity. We also characterized the role of C-terminal merlin residues in the regulation of proliferation, phosphorylation, and intramolecular associations. In contrast to previous reports, we demonstrated that both merlin isoforms are able to suppress cell proliferation, whereas C-terminally mutated merlin constructs showed reduced growth inhibition. Phosphorylation serves as a mechanism to regulate the tumor suppressive activity of merlin. The C-terminal serine 518 is phosphorylated in response to both p21-activated kinase (PAK) and protein kinase A (PKA), which inactivates the growth inhibitory function of merlin. However, at least three differentially phosphorylated forms of the protein exist. In this study we demonstrated that also the N-terminus of merlin is phosphorylated by AGC kinases, and that both PKA and Akt phosphorylate merlin at serine 10 (S10). We evaluated the impact of this N-terminal tail phosphorylation, and showed that the phosphorylation state of S10 is an important regulator of merlin s ability to modulate cytoskeletal organization but also regulates the stability of the protein. In summary, this study describes the functional effect of merlin specific regions. We demonstrate that both S10 in the N-terminal tail and residues E545-E547 in the C-terminus are essential for merlin activity and function.

Epithelial sodium channel in airway epithelium of the newborn infant : Implications for postnatal pulmonary adaptation

The aim of the present thesis was to study the role of the epithelial sodium channel (ENaC) in clearance of fetal lung fluid in the newborn infant by measurement of airway epithelial expression of ENaC, of nasal transepithelial potential difference (N-PD), and of lung compliance (LC). In addition, the effect of postnatal dexamethasone on airway epithelial ENaC expression was measured in preterm infants with bronchopulmonary dysplasia (BPD). The patient population was formed of selected term newborn infants born in the Department of Obstetrics (Studies II-IV) and selected preterm newborn infants treated in the neonatal intensive care unit of the Hospital for Children and Adolescents (Studies I and IV) of the Helsinki University Central Hospital in Finland. A small population of preterm infants suffering from BPD was included in Study I. Studies I, III, and IV included airway epithelial measurement of ENaC and in Studies II and III, measurement of N-PD and LC. In Study I, ENaC expression analyses were performed in the Research Institute of the Hospital for Sick Children in Toronto, Ontario, Canada. In the following studies, analyses were performed in the Scientific Laboratory of the Hospital for Children and Adolescents. N-PD and LC measurements were performed at bedside in these hospitals. In term newborn infants, the percentage of amiloride-sensitive N-PD, a surrogate for ENaC activity, measured during the first 4 postnatal hours correlates positively with LC measured 1 to 2 days postnatally. Preterm infants with BPD had, after a therapeutic dose of dexamethasone, higher airway epithelial ENaC expression than before treatment. These patients were subsequently weaned from mechanical ventilation, probably as a result of the clearance of extra fluid from the alveolar spaces. In addition, we found that in preterm infants ENaC expression increases with gestational age (GA). In preterm infants, ENaC expression in the airway epithelium was lower than in term newborn infants. During the early postnatal period in those born both preterm and term airway epithelial βENaC expression decreased significantly. Term newborn infants delivered vaginally had a significantly smaller airway epithelial expression of αENaC after the first postnatal day than did those delivered by cesarean section. The functional studies showed no difference in N-PD between infants delivered vaginally and by cesarean section. We therefore conclude that the low airway epithelial expression of ENaC in the preterm infant and the correlation of N-PD with LC in the term infant indicate a role for ENaC in the pathogenesis of perinatal pulmonary adaptation and neonatal respiratory distress. Because dexamethasone raised ENaC expression in preterm infants with BPD, and infants were subsequently weaned from ventilator therapy, we suggest that studies on the treatment of respiratory distress in the preterm infant should include the induction of ENaC activity.

The church must become the people of Soweto : Manas Buthelezi’s existential-Christocentric understanding of the church

The aim of this study has been to discern what Manas Buthelezi (1935-), a black South African Lutheran theologian and later also a bishop, regards as the requirements a church has to fulfill in order to be credible in the apartheid society. Buthelezi’s dissertation and several articles written between the years 1968 and 1993 are the sources of this study. Also the lectures held in Heidelberg in 1972 are referred to. Systematic analysis is the method used. The question of the credibility of the church is studied through three concepts that play an important role in Buthelezi’s ecclesiological thought, namely the wholeness of life, incarnation and liberation. The notion of the wholeness of life stems from the African tradition. Buthelezi takes the concept into the Christian church: the church should realize that God is the Creator of all life and Christ the lord of every aspect of human existence. Life is one entity coram Deo. However, the church is not to become the world; solidarity between the two must remain critical as the church is also called to play a prophetic role in the society. The church is in an open relationship with the world. It has a unique message of forgiveness and reconciliation. Nevertheless, the message is not a possession of the church but it is addressed to the whole world. The meaning of incarnation comes close to that of the wholeness of life. Following the example of Christ’s incarnation, the church must become human in the reality of the people. The church in Soweto is to become the people of Soweto, that is, the church must become as vulnerable as the people are. An incarnate church cannot be immune to the oppression that people experience, because the people are the church. The church is therefore bound to suffer. Buthelezi’s theology of the cross is pragmatic: the suffering of the church aims at the liberation of the oppressed. At times the physical presence of the church by the side of the suffering people is the only way to preach the incarnate gospel. In the South Africa of the late 1960s onwards the liberation of the oppressed black people was high on the agenda of Black Theology. As a leader of the early South African Black Theology, Buthelezi is concerned about the racial injustice in his country. He urges the churches to join the struggle against it as one people of God. The notions of liberation and the wholeness of life emerge in Buthelezi’s holistic understanding of liberation that involves the inner liberation of the black spirit and the liberation of the economic, social and political aspects of life. Interpreting Tillich’s correlation method in the South African situation, and also paralleling other liberation theologians, Buthelezi takes the existential situation of the people as the starting point for liberation. The gospel has to respond to the existential questions of people. The church is called to work for the liberation of society but it must also be liberated itself. Buthelezi initiated the LWF statement on the status confessionis in South Africa (1977). In line with the statement, he calls for church unity on the human level. For the unity to be true, it has to be experienced on the grassroots’ level. All the three concepts covered urge the church to come down from any ivory tower and out of any spiritual haven it might hide in. A lot of the credibility of the church derives from the behavior of the people. Buthelezi’s concentration on how the people who constitute the church should live their faith leaves less attention to how God constitutes the church. I have labeled Buthelezi’s understanding of the church existential-Christocentric due to the emphasis he lays on the need of the church to take the existential situation of the people seriously and on the other hand, on Christ as the exemplar for the church.

Lymphatic vessels in health and disease: Role of the VEGF-C/VEGFR-3 pathway and the transcription factor FOXC2

The circulatory system consists of two vessel types, which act in concert but significantly differ from each other in several structural and functional aspects as well as in mechanisms governing their development. The blood vasculature transports oxygen, nutrients and cells to tissues whereas the lymphatic vessels collect extravasated fluid, macromolecules and cells of the immune system and return them back to the blood circulation. Understanding the molecular mechanisms behind the developmental and functional regulation of the lymphatic system long lagged behind that of the blood vasculature. Identification of several markers specific for the lymphatic endothelium, and the discovery of key factors controlling the development and function of the lymphatic vessels have greatly facilitated research in lymphatic biology over the past few years. Recognition of the crucial importance of lymphatic vessels in certain pathological conditions, most importantly in tumor metastasis, lymphedema and inflammation, has increased interest in this vessel type, for so long overshadowed by its blood vascular cousin. VEGF-C (Vascular Endothelial Growth Factor C) and its receptor VEGFR-3 are essential for the development and maintenance of embryonic lymphatic vasculature. Furthermore, VEGF-C has been shown to be upregulated in many tumors and its expression found to positively correlate with lymphatic metastasis. Mutations in the transcription factor FOXC2 result in lymphedema-distichiasis (LD), which suggests a role for FOXC2 in the regulation of lymphatic development or function. This study was undertaken to obtain more information about the role of the VEGF-C/VEGFR-3 pathway and FOXC2 in regulating lymphatic development, growth, function and survival in physiological as well as in pathological conditions. We found that the silk-like carboxyterminal propeptide is not necessary for the lymphangiogenic activity of VEGF-C, but enhances it, and that the aminoterminal propeptide mediates binding of VEGF-C to the neuropilin-2 coreceptor, which we suggest to be involved in VEGF-C signalling via VEGFR-3. Furthermore, we found that overexpression of VEGF-C increases tumor lymphangiogenesis and intralymphatic tumor growth, both of which could be inhibited by a soluble form of VEGFR-3. These results suggest that blocking VEGFR-3 signalling could be used for prevention of lymphatic tumor metastasis. This might prove to be a safe treatment method for human cancer patients, since inhibition of VEGFR-3 activity had no effect on the normal lymphatic vasculature in adult mice, though it did lead to regression of lymphatic vessels in the postnatal period. Interestingly, in contrast to VEGF-C, which induces lymphangiogenesis already during embryonic development, we found that the related VEGF-D promotes lymphatic vessel growth only after birth. These results suggest, that the lymphatic vasculature undergoes postnatal maturation, which renders it independent of ligand induced VEGFR-3 signalling for survival but responsive to VEGF-D for growth. Finally, we show that FOXC2 is necessary for the later stages of lymphatic development by regulating the morphogenesis of lymphatic valves, as well as interactions of the lymphatic endothelium with vascular mural cells, in which it cooperates with VEGFR-3. Furthermore, our study indicates that the absence of lymphatic valves, abnormal association of lymphatic capillaries with mural cells and an increased amount of basement membrane underlie the pathogenesis of LD. These findings have given new insight into the mechanisms of normal lymphatic development, as well as into the pathogenesis of diseases involving the lymphatic vasculature. They also reveal new therapeutic targets for the prevention and treatment of tumor metastasis and lymphatic vascular failure in certain forms of lymphedema. Several interesting questions were posed that still need to be addressed. Most importantly, the mechanism of VEGF-C promoted tumor metastasis and the molecular nature of the postnatal lymphatic vessel maturation remain to be elucidated.

Characterization of the molecular components and function of BARE-1, Hin-Mu and Mu transposition machineries

Transposable elements, transposons, are discrete DNA segments that are able to move or copy themselves from one locus to another within or between their host genome(s) without a requirement for DNA homology. They are abundant residents in virtually all the genomes studied, for instance, the genomic portion of TEs is approximately 3% in Saccharomyces cerevisiae, 45% in humans, and apparently more than 70% in some plant genomes such as maize and barley. Transposons plays essential role in genome evolution, in lateral transfer of antibiotic resistance genes among bacteria and in life cycle of certain viruses such as HIV-1 and bacteriophage Mu. Despite the diversity of transposable elements they all use a fundamentally similar mechanism called transpositional DNA recombination (transposition) for the movement within and between the genomes of their host organisms. The DNA breakage and joining reactions that underlie their transposition are chemically similar in virtually all known transposition systems. The similarity of the reactions is also reflected in the structure and function of the catalyzing enzymes, transposases and integrases. The transposition reactions take place within the context of a transposition machinery, which can be particularly complex, as in the case of the VLP (virus like particle) machinery of retroelements, which in vivo contains RNA or cDNA and a number of element encoded structural and catalytic proteins. Yet, the minimal core machinery required for transposition comprises a multimer of transposase or integrase proteins and their binding sites at the element DNA ends only. Although the chemistry of DNA transposition is fairly well characterized, the components and function of the transposition machinery have been investigated in detail for only a small group of elements. This work focuses on the identification, characterization, and functional studies of the molecular components of the transposition machineries of BARE-1, Hin-Mu and Mu. For BARE-1 and Hin-Mu transpositional activity has not been shown previously, whereas bacteriophage Mu is a general model of transposition. For BARE-1, which is a retroelement of barley (Hordeum vulgare), the protein and DNA components of the functional VLP machinery were identified from cell extracts. In the case of Hin-Mu, which is a Mu-like prophage in Haemophilus influenzae Rd genome, the components of the core machinery (transposase and its binding sites) were characterized and their functionality was studied by using an in vitro methodology developed for Mu. The function of Mu core machinery was studied for its ability to use various DNA substrates: Hin-Mu end specific DNA substrates and Mu end specific hairpin substrates. The hairpin processing reaction by MuA was characterized in detail. New information was gained of all three machineries. The components or their activity required for functional BARE-1 VLP machinery and retrotransposon life cycle were present in vivo and VLP-like structures could be detected. The Hin-Mu core machinery components were identified and shown to be functional. The components of the Mu and Hin-Mu core machineries were partially interchangeable, reflecting both evolutionary conservation and flexibility within the core machineries. The Mu core machinery displayed surprising flexibility in substrate usage, as it was able to utilize Hin-Mu end specific DNA substrates and to process Mu end DNA hairpin substrates. This flexibility may be evolutionarily and mechanistically important.

EU Accession and FDI inflows : The cases of the Czech Republic and Slovakia

Central and East European countries have faced a difficult process of transition since the dissolution of the Soviet bloc. Ten transition countries (Hungary, Poland, teh Czech Republic, Slovakia, Slovenia, Lithuania, Latvia, Estonia, Bulgaria and Romania have chosen to join the EU and have moulded their transition reforms to ensure the compliance of their legal and institutional framework with EU requirements. The high levels of FDI attracted by the candidate countries for EU membership had been attributed to rapid transition of the countries aiming to join the European Union and the fact that favourable evaluations by EU authorities of the progress made by the candidates had a large impact on improving investor confidence. The aim of this paper is to investigate the reform strategies of the Czech Republic and Slovakia undertaken when the countries were preparing for EU membership and the dynamics of FDI inflows into these economies. Subsequently a comparative analysis of FDI stocks in these countries is conducted. We find that both countries faced similar economic challenges in implementing structural and institutional reforms. In accordance with EU requirements the Czech Republic and Slovakia have perfected their legal and institutional framework, increased the authority of regulatory and supervisory bodies and focused on implementation of new or amended legislation. During the period of the analysis (1998 - 2007) the Czech Republic and Slovakia have attracted increasing amounts of FDI. Comparative analysis in terms of important determinants of FDI reveals further similar features: macroeconomic stability; an open and liberalised market; low labour costs compared to EU-15 and a similar breakdown of FDI inflows by investor country. Consequently, the fact that the Czech Republic received much larger volumes of net FDI inflows could be attributed to the difference in market size between the two states. This conclusion is consistent with previous empirical studies that list market size among the main determinants of FDI. However, when we look at FDI as a percentage of GDP the evidence is more mixed. In 2004 - 2007, Slovakia has surpassed the Czech Republic twice. Whether this tendency will persist remains to be seen. The analysis in this paper based on empirical data. However, the choice of the method, namely case studies and comparative analysis, means that the conclusions of this study are theoretical and remain to be further tested in quantitative models.

Quest for authenticity - representation of the Sami image in Christmas tourism

Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.

Population projection for Namibia 2011-2020 - With an estimation of the impact of HIV/AIDS

This study presents a population projection for Namibia for years 2011–2020. In many countries of sub-Saharan Africa, including Namibia, the population growth is still continuing even though the fertility rates have declined. However, many of these countries suffer from a large HIV epidemic that is slowing down the population growth. In Namibia, the epidemic has been severe. Therefore, it is important to assess the effect of HIV/AIDS on the population of Namibia in the future. Demographic research on Namibia has not been very extensive, and data on population is not widely available. According to the studies made, fertility has been shown to be generally declining and mortality has been significantly increasing due to AIDS. Previous population projections predict population growth for Namibia in the near future, yet HIV/AIDS is affecting the future population developments. For the projection constructed in this study, data on population is taken from the two most recent censuses, from 1991 and 2001. Data on HIV is available from HIV Sentinel Surveys 1992–2008, which test pregnant women for HIV in antenatal clinics. Additional data are collected from different sources and recent studies. The projection is made with software (EPP and Spectrum) specially designed for developing countries with scarce data. The projection includes two main scenarios which have different assumptions concerning the development of the HIV epidemic. In addition, two hypothetical scenarios are made: the first considering the case where HIV epidemic would never have existed and the second considering the case where HIV treatment would never have existed. The results indicate population growth for Namibia. Population in the 2001 census was 1.83 million and is projected to result in 2.38/2.39 million in 2020 in the first two scenarios. Without HIV, population would be 2.61 million and without treatment 2.30 million in 2020. Urban population is growing faster than rural. Even though AIDS is increasing mortality, the past high fertility rates still keep young adult age groups quite large. The HIV epidemic shows to be slowing down, but it is still increasing the mortality of the working-aged population. The initiation of HIV treatment in 2004 in the public sector seems to have had an effect on many projected indicators, diminishing the impact of HIV on the population. For example, the rise of mortality is slowing down.

Governmental rationalities and the local dimension of European politics. A study of the Interreg IV programme "Alpenrhein-Bodensee-Hochrhein"

The thesis aims at investigating the local dimension of the EU cohesion policy through the utilization of an alternative approach, which aims at the analysis of discourse and structures of power. The concrete case under analysis is the Interreg IV programme “Alpenrhein-Bodensee-Hochrhein”, which is conducted in the border region between Germany, Switzerland, Austria and the principality of Liechtenstein. The main research question is stated as such: What governmental rationalities can be found at work in the field of EU cross-border cooperation programmes? How is directive action and cooperation envisioned? How coherent are the different rationalities, which are found at work? The theoretical framework is based on a Foucaultian understanding of power and discourse and utilizes the notion of governmentalities as a way to de-stabilize the understanding of directive action and in order to highlight the dispersed and heterogeneous nature of governmental activity. The approach is situated within the general field of research on the European Union connected to basic conceptualisations such as the nature of power, the role of discourse and modes of subjectification. An approach termed “analytics of government”, based on the work of researchers like Mitchell Dean is introduced as the basic framework for the analysis. Four dimensions (visiblities, subjectivities, techniques/practices, problematisations) are presented as a set of tools with which governmental regimes of practices can be analysed. The empirical part of the thesis starts out with a discussion of the general framework of the European Union's cohesion policy and places the Interreg IV Alpenrhein-Bodensee-Hochrhein programme in this general context. The main analysis is based on eleven interviews which were conducted with different individuals, participating in the programme on different levels. The selection of interview partners aimed at maximising heterogeneity through including individuals from all parts of the programme region, obtaining different functions within the programme. The analysis reveals interesting aspects pertaining to the implementation and routine aspects of work within initiatives conducted under the heading of the EU cohesion policy. The central aspects of an Interreg IV Alpenrhein-Bodensee-Hochrhein – governmentality are sketched out. This includes a positive perception of the work atmosphere, administrative/professional characterisation of the selves and a de-politicization of the programme. Characteristic is the experience of tensions by interview partners and the use of discoursive strategies to resolve them. Negative perceptions play an important role for the specific governmental rationality. The thesis contributes to a better understanding of the local dimension of the European Union cohesion policy and questions established ways of thinking about governmental activity. It provides an insight into the working of power mechanisms in the constitution of fields of discourse and points out matters of practical importance as well as subsequent research questions.

Quest for authenticity - representation of the Sami image in Christmas tourism

Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.

Väkivalta, antisemitismi ja konflikti Mel Gibsonin elokuvassa The Passion of The Christ

Tutkielman tarkoituksena on tutkia Mel Gibsonin elokuvaa The Passion of the Christ. Tarkastelussa mukana on myös Gibsonin muu tuotanto. Tutkielma edustaa poikkitieteellistä lähestymistapaa käyttäen eksegetiikan apuvälineitä kuten lähdekritiikkiä, mutta myös elokuvatutkimuksen välineitä. Tutkimuskysymyksiä nousee lähinnä kaksi, joista seuraa kolmas kysymys: 1. Onko elokuva juutalaisvastainen? Tarkastelen lähdekritiikin avulla mitä evankeliumeja Gibson on käyttänyt elokuvassaan. Mitä muita lähteitä hän on käyttänyt? Mikä on Gibsonin omaa ilmaisua? 2. Miksi elokuva on väkivaltainen? Mitä väkivalta palvelee elokuvassa? 3. Millainen on elokuvamaailman konflikti? Pohdin elokuvamaailman sisälle rakennettua konfliktia, mutta viittaan sillä myös konfliktiin, jonka elokuva itsessään synnytti. Kysymysten ratkaisu vaatii elokuvassa käytettyjen lähteiden tutkimista, mutta myös kysymysten tarkastelua osana laajempaa kokonaisuutta, jossa on mukana koko Gibsonin elokuvatuotanto. On myös selvää, ettei Gibson ole yhtä kuin hänen elokuvansa, mutta toisaalta hänen elokuviaan ei voi tarkastella irrotettuna ohjaajasta itsestään. Ensimmäisessä luvussa tarkastelen elokuvaa ilmiönä ja elokuvasta käytyä ennakkokeskustelua. Luvussa kaksi tarkastelen Gibsonin taustaa. Millaisista lähtökohdista Gibson lähti tekemään elokuvaa? Luvussa kolme esittelen käsikirjoituksesta alkavan elokuvan yleisen tuotantoprosessin. Tutkielman päälähteenä olen käyttänyt Brentanon kirjaa The Dolorous Passion of Our Lord Jesus Christ. Kirja pohjautuu 1800-luvulla eläneen katolisen nunnan, Anne Catherine Emmerichin näkyihin. Luvussa neljä tarkastelen Gibsonin muuta tuotantoa, ja tuon keskusteluun mukaan Scorsesen elokuvan Jeesuksesta. Gibsonin muu tuotanto on jäänyt tutkijoilta liian vähälle huomiolle. Elokuva The Passion of the Christ on nähtävä osana Gibsonin muuta tuotantoa. Näin ollen elokuvaa The Passion of the Christ voidaan ymmärtää paremmin. Luvussa viisi käyn elokuvan The Passion of the Christ läpi kappale kerrallaan tutkimalla, mitä lähteitä Gibson on käyttänyt elokuvassaan. Mitä hän on ottanut evankeliumeista, mitä Emmerichiltä ja mikä on hänen omaa ilmaisuaan? Luvussa kuusi käyn läpi elokuvan vastaanottoa niin raamatuntutkijoiden kuin suuren yleisön parissa. Tutkielmassa todetaan, ettei Gibson ole antisemitisti, vaan ksenofobinen rasisti. Hänen elokuvansa ovat ksenofobisesti rasistisia. Gibsonin kaikista elokuvista on löydettävissä itseään toistavia piirteitä, joissa esiintyy muukalaiskammoa ja väkivaltaa. Gibsonin nimittäminen antisemitistiksi ei tekisi Gibsonille oikeutta. Juutalaiset ovat vain osa laajempaa kokonaisuutta. Väkivalta palvelee kaikissa elokuvissa uuden, Jumalan valtakunnan syntymistä. Konflikti syntyy uuden ja vanhan valtakunnan kansalaisten välillä. Uhrien veren kautta syntyy Jumalan valtakunta. Johtopäätöksillä on merkitystä niin Gibsonin kuin hänen elokuviensa ymmärtämiselle. Elokuvan The Passion of the Christ tulevissa tutkimuksissa on otettava huomioon, ei vain Gibsonin tausta ja lähteet, vaan myös Gibsonin muu elokuvatuotanto.

Victims of the White War or Rebellions of the Green Revolution? Bolivian Indigenous Women Prisoners' Position in the "War on Drugs" Explored through a Criminological Gaze

Tässä tutkielmassa tarkastellaan Bolivialaisten naisvankien (alkuperäisväestön) ja globaalin huumesodan ("War on Drugs") välistä yhteyttä. Keskustelu sijoitetaan laajemmin kokan viljelyn politiikkaan ja alkuperäisväestön kulttuuriin. Kokaa viljeleviä köyhiä maalaisia, joista huomattava osa on naisia, on vangittu Boliviassa kiihtyvää tahtia viime vuosikymmeninä. Moni naisista on kokan tuotannossa ja kaupassa mukana, sillä se on monesti ainoa keino taloudelliseen selviämiseen. Yleisesti ottaen naisvangit ja naisrikolliset ovat marginaalinen ilmiö. Kansainvälisesti tarkasteltuna naisvankien suhteellinen osuus koko vankilaväestöstä on noin 5,2 % (keskiarvo). Boliviassa osuus on vaihdellut 6,1 %:n ja 17,1 %:n välillä vuosina 2000-2008. Naisvankien määrä yleisesti ottaen on ollut rajussa kasvussa, suurin syy naisten vangitsemiseen on huumausaineisiin liittyvät rikokset. Näyttää myös siltä että vähemmistöt ja etnisen taustan omaavat henkilöt ovat yliedustettuina vankilaväestössä. Bolivia seuraa tätä kansainvälistä trendiä. Tämä tutkielma on rajattu kysymyksiin Bolivian intiaaniperäisten naisten osuudesta maan huumerikollisuudessa, sekä heidän suhteellisen korkeaa vangitsemisastetta selittäviin yhteiskunnallisiin tekijöihin. Kysymykset sukupuolesta, etnisyydestä ja kokan viljelyn politiikasta ovat keskiössä. Yleisiä kriminologisia teorioita peilataan kriittisesti suhteessa aineistoon ja Bolivian kontekstiin. Huumesodan ja Bolivian ankaran huumelainsäädännön seurauksista keskustellaan kriittisesti, sekä pohditaan köyhän alkuperäisväestön massavangitsemisen tarpeellisuutta. Tutkimuskysymykseni ovat: mitkä tekijät selittävät kohtuullisen korkean intiaaniperäisten naisvankien määrän Boliviassa, ja mikä on heidän asemansa globaalissa huumesodassa? Tutkielmassa on analysoitu kvantitatiivista ja kvalitatiivista aineistoa. Päälähteenä on ollut Bolivian tilastokeskuksen tuottamat rikostilastot. Tutkielman tärkeimpänä löydöksenä voidaan pitää havaintoa, että vastoin tiettyjä olettamuksia, intiaaniperäiset naiset ovat hyvinkin aktiivisia perinteisesti miehisiksi käsitetyillä aloilla kuten rikollisuudessa ja politiikassa. Tutkielmassa osoitetaan myös, että pidätysten määrät ovat moninkertaistuneet muutamassa vuosikymmenessä. Koska kokan viljelyssä on kyse pääasiallisesti taloudellisesta toimeentulosta, tämä tutkielma kysyy, onko hengissä pysyminen rikos?

Functional imaging of peripheral vision and dorsal stream function in the human cerebral cortex

Visual information processing in brain proceeds in both serial and parallel fashion throughout various functionally distinct hierarchically organised cortical areas. Feedforward signals from retina and hierarchically lower cortical levels are the major activators of visual neurons, but top-down and feedback signals from higher level cortical areas have a modulating effect on neural processing. My work concentrates on visual encoding in hierarchically low level cortical visual areas in human brain and examines neural processing especially in cortical representation of visual field periphery. I use magnetoencephalography and functional magnetic resonance imaging to measure neuromagnetic and hemodynamic responses during visual stimulation and oculomotor and cognitive tasks from healthy volunteers. My thesis comprises six publications. Visual cortex forms a great challenge for modeling of neuromagnetic sources. My work shows that a priori information of source locations are needed for modeling of neuromagnetic sources in visual cortex. In addition, my work examines other potential confounding factors in vision studies such as light scatter inside the eye which may result in erroneous responses in cortex outside the representation of stimulated region, and eye movements and attention. I mapped cortical representations of peripheral visual field and identified a putative human homologue of functional area V6 of the macaque in the posterior bank of parieto-occipital sulcus. My work shows that human V6 activates during eye-movements and that it responds to visual motion at short latencies. These findings suggest that human V6, like its monkey homologue, is related to fast processing of visual stimuli and visually guided movements. I demonstrate that peripheral vision is functionally related to eye-movements and connected to rapid stream of functional areas that process visual motion. In addition, my work shows two different forms of top-down modulation of neural processing in the hierachically lowest cortical levels; one that is related to dorsal stream activation and may reflect motor processing or resetting signals that prepare visual cortex for change in the environment and another local signal enhancement at the attended region that reflects local feed-back signal and may perceptionally increase the stimulus saliency.