Mediated music makers : Constructing author images in popular music

The subject of the thesis is the mediated construction of author images in popular music. In the study, the construction of images is treated as a process in which artists, the media and the members of the audience participate. The notions of presented, mediated and compiled author images are used in explaining the mediation process and the various authorial roles of the agents involved. In order to explore the issue more closely, I analyse the author images of a group of popular music artists representing the genres of rock, pop and electronic dance music. The analysed material consists mostly of written media texts through which the artists authorial roles and creative responsibilities are discussed. Theoretically speaking, the starting points for the examination lie in cultural studies and discourse analysis. Even though author images may be conceived as intertextual constructions, the artist is usually presented as a recognizable figure whose purpose is to give the music its public face. This study does not, then, deal with musical authors as such, but rather with their public images and mediated constructions. Because of the author-based functioning of popular music culture and the idea of the artist s individual creative power, the collective and social processes involved in the making of popular music are often superseded by the belief in a single, originating authorship. In addition to the collective practices of music making, the roles of the media and the marketing machinery complicate attempts to clarify the sharing of authorial contributions. As the case studies demonstrate, the differences between the examined author images are connected with a number of themes ranging from issues of auteurism and stardom to the use of masked imagery and the blending of authorial voices. Also the emergence of new music technologies has affected not only the ways in which music is made, but also how the artist s authorial status and artistic identity is understood. In the study at hand, the author images of auteurs, stars, DJs and sampling artists are discussed alongside such varied topics as collective authorship, evaluative hierarchies, visual promotion and generic conventions. Taken altogether, the examined case studies shed light on the functioning of popular music culture and the ways in which musical authorship is (re)defined.

Intercultural Learning and Hybridity in the Culture Laboratory

The number of immigrant students in vocational education and training is steadily increasing in Finland. This poses challenges for teachers and schools. This research focuses on emerging questions of intercultural learning in the context of immigrant training, and on a method the Culture Laboratory that was developed in an attempt to respond to the challenges. The main methodological and theoretical framework lies in cultural-historical activity theory, developmental work research, and in the concepts of the intercultural and hybridity. The empirical material consists of videotaped recordings of discussions in the Culture Laboratory. The five main research questions focused on the strengths and limitations of the Culture Laboratory as a tool for intercultural learning, the significance of disturbances in it, the potential of suggestions for intercultural learning, paper as a mediating artifact , and the concept of intercultural space. The findings showed that the Culture Laboratory offered a solid background for developing intercultural learning. The disturbances manifested revealed a multitude of scripts and activities. It was also suggested that the structure of expansive learning could start from externalization instead of internalization. The suggestions the participants made opened up a hybrid learning space for intercultural development, and offered a good springboard for new ideas. Learning in Paperland posed both challenges and opportunities for immigrant students, and different paper trails emerged. Intercultural space in the Culture Laboratory was a developmental zone in which a hybrid process of observing, comparing, and creating took place. Key words: intercultural learning, immigrant training, cultural-historical activity theory, developmental work research,

Beasts on Fields. Human-Wildlife Conflicts in Nature-Culture Borderlands

Human-wildlife conflicts are today an integral part of the rural development discourse. In this research, the main focus is on the spatial explanation which is not a very common approach in the reviewed literature. My research hypothesis is based on the assumption that human-wildlife conflicts occur when a wild animal crosses a perceived borderline between the nature and culture and enters into the realms of the other. The borderline between nature and culture marks a perceived division of spatial content in our senses of place. The animal subject that crosses this border becomes a subject out of place meaning that the animal is then spatially located in a space where it should not be or where it does not belong according to tradition, custom, rules, law, public opinion, prevailing discourse or some other criteria set by human beings. An appearance of a wild animal in a domesticated space brings an uncontrolled subject into that space where humans have previously commanded total control of all other natural elements. A wild animal out of place may also threaten the biosecurity of the place in question. I carried out a case study in the Liwale district in south-eastern Tanzania to test my hypothesis during June and July 2002. I also collected documents and carried out interviews in Dar es Salaam in 2003. I studied the human-wildlife conflicts in six rural villages, where a total of 183 persons participated in the village meetings. My research methods included semi-structured interviews, participatory mapping, questionnaire survey and Q- methodology. The rural communities in the Liwale district have a long-history of co-existing with wildlife and they still have traditional knowledge of wildlife management and hunting. Wildlife conservation through the establishment of game reserves during the colonial era has escalated human-wildlife conflicts in the Liwale district. This study shows that the villagers perceive some wild animals differently in their images of the African countryside than the district and regional level civil servants do. From the small scale subsistence farmers point of views, wild animals continue to challenge the separation of the wild (the forests) and the domestics spaces (the cultivated fields) by moving across the perceived borders in search of food and shelter. As a result, the farmers may loose their crops, livestock or even their own lives in the confrontations of wild animals. Human-wildlife conflicts in the Liwale district are manifold and cannot be explained simply on the basis of attitudes or perceived images of landscapes. However, the spatial explanation of these conflicts provides us some more understanding of why human-wildlife conflicts are so widely found across the world.

Relocating the American Dream : The America of the 1960s as Portrayed by the New Journalists Norman Mailer, Hunter S. Thompson, and Tom Wolfe

The concept of the American Dream was subject to a strong re-evaluation process in the 1960s, as counterculture became a prominent force in American society. A massive generation of young people, moved by the Vietnam War, the hippie movement, and psychedelic experimentation, created substantial social turbulence in their efforts to break out of conventional patterns and to create a new kind of society. This thesis outlines and analyses the concept of the American Dream in popular imagination through three works of new journalism. My primary data consists of Tom Wolfe’s The Electric Kool-Aid Acid Test (1967), Hunter S. Thompson’s Fear and Loathing in Las Vegas: A Savage Journey to the Heart of the American Dream (1971), and Norman Mailer’s Armies of the Night: History as a Novel, the Novel as History (1968). In defining the American Dream, I discuss the history of the concept as well as its manifestations in popular culture. Because of its elusive and amorphous nature, the concept of the American Dream can only be examined in cultural texts that portray the values, sentiments, and customs of a certain era. I have divided the analytical section of my thesis into three parts. In the first part I examine how the authors discuss the American society of their time in relation to ideology, capitalism, and the media. In the second part I focus on the Vietnam War and the controversy it creates in relation to the notions of freedom and patriotism. In the third part I discuss how the authors portray the countercultural visions of a better America that challenged the traditional interpretations of the American Dream. I also discuss the dark side of the new dream: the problems and disillusions that came with the effort to change the world. This thesis is an effort to trace the relocation of the American Dream in the context of the 1960s counterculture and new journalism. It hopes to provide a valuable addition to the cultural history of the sixties and to the effort of conceptualizing the American Dream.

Nainen, mies, rakkaus, seksi : Heterosuhteen kulku, kulttuurinen malli ja sitä selittävät diskurssit kahden omaelämäkerta-aineiston valossa

The subject matter of this study is the cultural knowledge concerning romantic male-female relationships in autobiographies written by so called ordinary Finnish men and women born between 1901 and 1965. The research data (98 autobiographies) is selected from two collections by the Finnish Literature Society s folklore archives in the early 1990 s. Autobiographies are cultural representations where negotiation of shared cultural models and personal meanings given to hetero-relationship is evident in an interesting manner. In this research I analyze autobiographies as a written folklore genre. Information concerning male-female relationships is being analyzed using theoretically informed close readings thematic analysis, intertextual reading and reflexive reading. Theoretical implications stem from cognitive anthropology (the idea of cultural models) and an adaptation of discourse theory inspired by Michel Foucault. The structure of the analysis follows the structure of the shared knowledge concerning romantic male-female relationship: the first phase of analysis presents the script of a hetero-relationship and then moves into the actual structure, the cultural model of a relationship. The components of the model of relationship are, as mentioned in the title of the research, woman, man, love and sex. The research shows that all the writers share this basic knowledge concerning a heterosexual relationship despite their age, background or gender. Also the conflicts described and experienced in the relationships of the writers were similar throughout the timespan of the early 1900 s to 1990 s: lack of love, inability to reconcile sexual desires, housework, sharing the responsibility of childcare and financial problems. The research claims that the conflicts in relationships are a major cause for the binary view on gender. When relationships are harmonious, there seems to be no need to see men and women as opposites. The research names five important discourses present in the meaning giving processes of autobiographers. In doing so, the stabile cultural model of male-female relationship widens to show the complexity and variation in data. In this way it is possible to detect some age and gender specific shifts and emphasis. The discourses give meaning to the components of the cultural model and determine the contents of womanhood, manhood, sexuality and love. The way these discourses are spread and their authority are different: the romantic discourse evident in the autobiographies appeal to the authority of love supreme love is the purpose of male-female relationship and it justifies sexuality. In this discourse sex can be the place for confluence of genders. The ideas of romantic love are widely spread in popular culture. Popular scientific discourse defines a relationship as a site to become a man and a woman either from a psychological or a biological point of view. Genders are seen as opposites. These ideas are often presented in media and their authority in science which is seen as infallible. The Christian discourse defines men and women: both should work for the benefit of the nuclear family under the undisputed authority of God. Marital love is based on Christian virtues and within marriage sexuality is acceptable. The discourse I ve named folk tradition defines women and men as guardians of home and offspring. The authority of folk tradition comes from universal truth based in experience and truths known to the mediators of this discourse grandparents, parents and other elders or peers. Societal discourse defines the hetero relationship as the mainstay of society. The authority in societal discourse stems from the laws and regulations that control relationship practices.

Rhetoric and Representation : Exploring the Cultural Meaning of the Natural Sciences in Contemporary Popular Science Writing and Literature

Kirjallisuuden- ja kulttuurintutkimus on viimeisten kolmen vuosikymmenen aikana tullut yhä enenevässä määrin tietoiseksi tieteen ja taiteen suhteen monimutkaisesta luonteesta. Nykyään näiden kahden kulttuurin tutkimus muodostaa oman kenttänsä, jolla niiden suhdetta tarkastellaan ennen kaikkea dynaamisena vuorovaikutuksena, joka heijastaa kulttuurimme kieltä, arvoja ja ideologisia sisältöjä. Toisin kuin aiemmat näkemykset, jotka pitävät tiedettä ja taidetta toisilleen enemmän tai vähemmän vastakkaisina pyrkimyksinä, nykytutkimus lähtee oletuksesta, jonka mukaan ne ovat kulttuurillisesti rakentuneita diskursseja, jotka kohtaavat usein samankaltaisia todellisuuden mallintamiseen liittyviä ongelmia, vaikka niiden käyttämät metodit eroavatkin toisistaan. Väitöskirjani keskittyy yllä mainitun suhteen osa-alueista popularisoidun tietokirjallisuuden (muun muassa Paul Davies, James Gleick ja Richard Dawkins) käyttämän kielen ja luonnontieteistä ideoita ammentavan kaunokirjallisuuden (muun muassa Jeanette Winterson, Tom Stoppard ja Richard Powers) hyödyntämien keinojen tarkasteluun nojautuen yli 30 teoksen kattavaa aineistoa koskevaan tyylin ja teemojen tekstianalyysiin. Populaarin tietokirjallisuuden osalta tarkoituksenani on osoittaa, että sen käyttämä kieli rakentuu huomattavassa määrin sellaisille rakenteille, jotka tarjoavat mahdollisuuden esittää todellisuutta koskevia argumentteja mahdollisimman vakuuttavalla tavalla. Tässä tehtävässä monilla klassisen retoriikan määrittelemillä kuvioilla on tärkeä rooli, koska ne auttavat liittämään sanotun sisällön ja muodon tiukasti toisiinsa: retoristen kuvioiden käyttö ei näin ollen edusta pelkkää tyylikeinoa, vaan se myös usein kiteyttää argumenttien taustalla olevat tieteenfilosofiset olettamukset ja auttaa vakiinnuttamaan argumentoinnin logiikan. Koska monet aikaisemmin ilmestyneistä tutkimuksista ovat keskittyneet pelkästään metaforan rooliin tieteellisissä argumenteissa, tämä väitöskirja pyrkii laajentamaan tutkimuskenttää analysoimalla myös toisenlaisten kuvioiden käyttöä. Osoitan myös, että retoristen kuvioiden käyttö muodostaa yhtymäkohdan tieteellisiä ideoita hyödyntävään kaunokirjallisuuteen. Siinä missä popularisoitu tiede käyttää retoriikkaa vahvistaakseen sekä argumentatiivisia että kaunokirjallisia ominaisuuksiaan, kuvaa tällainen sanataide tiedettä tavoilla, jotka usein heijastelevat tietokirjallisuuden kielellisiä rakenteita. Toisaalta on myös mahdollista nähdä, miten kaunokirjallisuuden keinot heijastuvat popularisoidun tieteen kerrontatapoihin ja kieleen todistaen kahden kulttuurin dynaamisesta vuorovaikutuksesta. Nykyaikaisen populaaritieteen retoristen elementtien ja kaunokirjallisuuden keinojen vertailu näyttää lisäksi, kuinka tiede ja taide osallistuvat keskusteluun kulttuurimme tiettyjen peruskäsitteiden kuten identiteetin, tiedon ja ajan merkityksestä. Tällä tavoin on mahdollista nähdä, että molemmat ovat perustavanlaatuisia osia merkityksenantoprosessissa, jonka kautta niin tieteelliset ideat kuin ihmiselämän suuret kysymyksetkin saavat kulttuurillisesti rakentuneen merkityksensä.

Approaching Sacred Pregnancy : The Cult of the Visitation and Narrative Altarpieces in Late Fifteenth-Century Florence

The study focuses on the Visitation as a narrative subject of altarpieces in late fifteenth-century Florence. Although the Visitation was a well-known story in both verbal and visual representations since the early medieval period, it became a popular subject of altarpieces only towards the end of the fifteenth century. In this study, the first part provides an overview of the complex religious and historical background to an emerging cult of the Visitation. Devotional practices focusing on the Visitation belong in a context of late medieval Marian devotion and in 1389 a new feast of the Visitation was introduced into the liturgical calendar of the Catholic Church. Because of the ongoing schism within the Catholic Church, the feast was not unanimously accepted across Western Europe until the later part of the fifteenth century. Contrary to a widely disseminated view, the feast of the Visitation cannot be associated with Franciscan spirituality, but was rather a clearly defined Dominican project that primarily emphasised the importance of peace and unity within the Christian Church. Simultaneously with the gradual acceptance of the new feast, visual representations of the Visitation began to appear at the centre of altarpieces. The Visitation exemplifies an increasing preference for narrative subjects within the genre of the altarpiece. The second part of the study presents an analysis of the concept of the narrative altarpiece and highlights the complexities involved in combining a narrative content with the traditional devotional function of the altarpiece. In detailed case studies some prominent art works produced in Florence between 1490 and 1503 are discussed within a framework of contextual analysis, narrative theory and iconography. Altarpieces by Domenico Ghirlandaio, Piero di Cosimo and Mariotto Albertinelli represent visual manifestations of a cult of the Visitation with roots in late medieval devotional practices. At the same time, the altarpieces highlight the multiple functions of altarpieces in a culture where art works responded to a variety of social and religious needs. Building on earlier studies, each case study presents new insights and evidence not considered in previous art historical research.

Lost in translation? : Translating allusions in two of Reginald Hill's Dalziel & Pascoe novels

This study examines strategies used to translate various thematic and character delineating allusions in two of Reginald Hill's detective novels, The Wood Beyond and On Beulah Height and their Swedish translations Det mörka arvet and Dalen som dränktes. In this study, thematic allusions and allusions used in character delineation are regarded as intertextual networks. Intertextual networks comprise all the texts that are in one way or another embedded into a text, all the texts referred to in it and even the texts somehow rejected from a text's own canon. Studying allusions as intertextual networks makes it warranted to pay minute attention to even the smallest of details. Seen together, these little details form extensive networks of meaning that readers use to interpret the text. Allusion can be defined as a reference, often covert or indirect, to another text in a way that brings into the text some of the associations of that other text. A text is here understood broadly, hence sources of allusions include all cultural texts from literature and history to cinema and televisions serials. Allusions are culture bound and each culture tends to allude to its own cultural products. The set of transcultural allusions is therefore fairly small. Translation strategies are translatorial ways of solving translation problems. Being culture-bound, allusions are potential translation problems. In order to transmit the thoughts evoked by the allusions in source text readers to the target text readers translators may add guidance to the translated text. Often guidance is not added, which may result in changes in handling of themes or character delineation, clear in the source text but confusing or incomprehensible in the target text. However, norms in target culture may not always allow the translators the possibility to make the text comprehensible. My analyses of translation strategies show that in the two translated novels studied minimum change is a very frequently used strategy. This results in themes and character delineation losing some of the effect they have in the source texts. Perhaps surprisingly, the result is very much the same even where it is possible to discern that the two translators have had differing translation principles. Keywords: allusions, intertextuality, literary translation, translation strategies, norms, crime fiction, Hill, Reginald

Ylirajaisia suhteita : Helsingin olympialaiset, Armi Kuusela ja ylikansallinen historia

In 1952 Helsinki hosted the Summer Olympic Games and Armi Kuusela, the current “Maiden of Finland”, was at the same time crowned Miss Universe. In popular history writing, these events have been designated as a crucial turning point – the end of an era marked by war and deprivation and the beginning of a modern, Western nation. Symptomatically, both events were marked by Finnish women’s sexual relationships with foreign men. The Olympics were shadowed by a concern over Finnish women’s “undue friendliness” with the Olympic guests, and Armi Kuusela's world tour was cut short by her surprise marriage in Tokyo and subsequent emigration to the Philippines. This study is an inquiry into the Helsinki Olympics and the public persona of Armi Kuusela from the point of view of transnational heterosexuality and the constitution of Finnish national identity. Methodologically the two main components of the study are intersectionality, defined here as a focus on the mutual histories and effects of discourses of gender, sexuality, race and nation; and transnational history as a way of exploring the ways that both nations and sexual subjects are embedded in global relations of power. The analysis proceeds by way of contextual and intertextual readings of various sources. Part one, centering on the Olympics, involves a campaign mounted by certain women’s organizations before the Games in order to educate young women about the potential dangers of the forthcoming international event as well as magazine and newspaper articles published during and after the Games concerning the encounter between young Finnish women and foreign, especially “Southern,” men. It places the debates during the Olympics within the framework of wartime understandings of women’s sexuality; the history of the concept of decency (siveellisyys); post-war population policy; the intersectional histories of conceptions pertaining to race and sexuality; and finally, the post-war concerns over women’s migration from rural areas to the capital city and their potential emigration abroad. Part two deals with the persona of Armi Kuusela and the public reception of her world tour and marriage, based on material from both Finland and the Philippines (newspapers, magazines, advertisements, books and films). It examines the persona of Armi Kuusela as a figure of national import in terms of the East/West divide; the racialized images of different geographic climates and Oriental “Others;” the meaning of whiteness in the Philippines; the significance of class and colonial history for the domestication of sexual and racial transgressions implied by an unconventional transnational marriage; as well as the cultural logics of transnational desire and its possible meanings for women in 1950s Finland. The study develops two arguments. First, it suggests that instead of being purely oppositional to national discourses, transnational desire may also be viewed as a product of these very discourses. Second, it claims that the national significance of both the Olympics and the persona of Armi Kuusela was due to the new points of comparison they both offered for national identity construction. In comparison with the sexualized Southern men at the Olympics and the racialized Orient in the representations of Armi Kuusela’s travels and marriage, Finland emerged as part of the civilized North, placed firmly within the perimeters of Western Europe. As such, both events mark a “whitening” of the Finnish people as well as a distancing from their previous designations in racial hierarchies. At the same time, however, the process of becoming a white nation inevitably meant complying with and reproducing racial hierarchies, rather than simply abolishing them.

Probiotic activity of Lactobacillus delbrueckii subsp. bulgaricus in the oral cavity

Yogurt consumption has been related to longevity of some populations living on the Balkans. Yogurt starter L. delbrueckii subsp. bulgaricus and Str. thermophilus have been recognized as probiotics with verified beneficial health effects. The oral cavity emerges as a arget for probiotic applications. Probiotics have demonstrated promising results in controlling dental diseases and oral yeast infections. However, L. bulgaricus despite its broad availability in dairy products has not been evaluated for probiotic activity in the mouth. These series of studies investigated in vitro properties of L. bulgaricus to outline its potential as an oral probiotic. Prerequisite probiotic properties in the mouth are resistance to oral defense mechanisms, adherence to saliva-coated surfaces, and inhibition of oral pathogens. L. bulgaricus strains showed a strain-dependent inhibition of oral streptococci and Aggregatibacter actinomycetemcomitans, whereas none of the dairy starter strains could affect growth of Porphyromonas gingivalis and Fusobacterium nucleatum. Adhesion is a factor contributing to colonization of the species at the target site. Radiolabeled L. bulgaricus strains and L. rhamnosus GG were tested for their ability to adhere to saliva-coated surfaces. The effects of lysozyme on adhesion and adhesion of Streptococcus sanguinis after lactobacilli pretreatment were also assessed. Adhesion of L. bulgaricus remained lower in comparison to L. rhamnosus GG. One L. bulgaricus strain showed binding frequency comparable to S. sanguinis. Lysozyme pretreatment significantly increased Lactobacillus adhesion. Low gelatinolytic activity was observed for all strains and no conversion of proMMP-9 to its active form was induced by L. bulgaricus. Safety assessment ruled out deleterious effects of L. bulgaricus on extracellular matrix structures. Cytokine response of oral epithelial cells was assessed by measuring IL-8 and TNF-α in cell culture supernatants. The effect of P. gingivalis on cytokine secretion after lactobacilli pretreatment was also assessed. A strain- and time-dependent induction of IL-8 was observed with live bacteria inducing the highest levels of cytokine secretion. Levels of TNF-α were low and only one of ten L. bulgaricus strains stimulated TNF-α secretion similar to positive control. The addition of P. gingivalis produced immediate reduction of cytokine levels within the first hours of incubation irrespective of lactobacilli strains co-cultured with epithelial cells. According to these studies strains among the L. delbrueckii subsp. bulgaricus species may have beneficial probiotic properties in the mouth. Their potential in prevention and management of common oral infectious diseases needs to be further studied.

In vitro development of islets from human adult pancreatic tissues

Transplantation of isolated islets from cadaver pancreas is a promising possibility for the optimal treatment of type 1 diabetes. The lack of islets is a major problem. Here we have investigated the possibility of generating islets in tissue culture of human pancreatic cells. We first reproduced a previously reported method of in vitro generation of endocrine cells from human adult pancreatic tissue. By tracing the bromodeoxyuridine-labeled cells in differentiated islet buds, we found that the pancreatic progenitor cells represented a subpopulation of cytokeratin 19 (CK19)-positive ductal cells. Serum-free medium and Matrigel overlay were essential for the endocrine differentiation. We then examined the involvement of preexisting islet cells in islet neogenesis. About 6-10% of endocrine cells dedifferentiated and acquired a transitional phenotype by coexpressing CK19. Significant cell proliferation was only observed in CK19-positive cells, but not in chromogranin A-positive endocrine cells. The in vitro-derived human islets were morphologically and functionally immature when compared with normal islets. Their insulin mRNA levels were only 4-5% of that found in fresh human islets, and glucose-stimulated insulin release was 3 times lower than that of control islets. Moreover, some immature endocrine cells coexpressed insulin and glucagon. After transplantation in nude mice, the in vitro-generated islets became mature with one type of hormone per endocrine cell. In addition, we also found that also in both fresh islet transplants many cells coexpressed endocrine markers and ductal marker CK19 as a sign of ductal to endocrine cell transition. Finally, we studied the effects of clinically used immunosuppressive drugs on precursor cell proliferation and differentiation. Mycophenolate mofetil (MMF) severely hampered duct-cell proliferation, and significantly reduced the total DNA content indicating its antiproliferative effect on the precursors. Tacrolimus mainly affected differentiated beta cells by decreasing the insulin content per DNA as well as the proportion of insulin-positive cells. Sirolimus and daclizumab did not show any individual or synergistic side effects suggesting that these drugs are amenable for use in clinical islet transplantation. In summary, we confirm the capacity of endocrine differentiation from progenitors present in the adult human pancreas. The plasticity of differentiated cell types of human pancreas may be a potential mechanism of human pancreas regeneration. Ductal cell differentiation into endocrine cells in transplanted islets may be an important factor in sustaining the long-term function of islet transplants. The immunosuppressive protocol is likely to be an important determinant of long-term clinical islet graft function. Moreover, these results provide new information on the mechanisms of pancreatic islet regeneration and provide the basis for the development of new strategies for the treatment of insulin deficient diabetes mellitus.

Fibroblast nemosis in malignant progression of epithelial cells

Paracrine regulation between the components of the tumour microenvironment cancer cells, activated fibroblasts, immune and endothelial cells is under intense investigation. The signals between the different cell types are mediated by soluble factors, such as growth factors, proinflammatory cytokines and proteolytic enzymes. Nemosis is an experimental in vitro model of fibroblast activation, leading to increased production of such mediators. Nemotic activation of fibroblasts occurs as they are forced to cluster thereby forming a multicellular spheroid. The aim of the present studies was to elucidate the mechanisms underlying the nemotic response of cancer-associated fibroblasts (CAF) and the role of nemosis in paracrine regulation between activated fibroblasts and benign and malignant epithelial cells. The results presented in this thesis demonstrate that the nemotic response of CAFs and normal fibroblasts differs, and inter-individual variations exist between fibroblast populations. In co-culture experiments, fibroblasts increased colony formation of squamous cell carcinoma (SCC) cells, and CAFs further augmented this, highlighting the tumour-evolving properties of CAFs. Furthermore, fibroblast monolayers in those co-cultures started to cluster spontaneously. This kind of spontaneous nemosis response might take place also in vivo, although more direct evidence of this still needs to be obtained. The HaCaT skin carcinoma progression model was used to study the effects of benign and malignant keratinocytes on fibroblast nemosis. Benign HaCaT cells inhibited fibroblast nemosis, observed as inhibition of cyclooxygenase 2 (COX-2) induction in nemotic spheroids. In contrast, malignant HaCaTs further augmented the nemotic response by increasing expression of COX-2 and the growth factors hepatocyte growth factor / scatter factor (HGF/SF) and vascular endothelial growth factor (VEGF), as well as causing a myofibroblastic differentiation of nemotic fibroblasts into fibroblasts resembling CAFs. On the other side of this reciprocal signalling, factors secreted into conditioned medium by the nemotic fibroblasts promoted proliferation and motility of the HaCaT cell lines. Notably, the nemotic fibroblast medium increased the expression of p63, a transcription factor linked to carcinogenesis, also in the highly metastatic HaCaT cells. These results emphasize the paracrine role of factors secreted by activated fibroblasts in driving tumour progression. We also investigated the epithelial-mesenchymal transition (EMT) of the HaCaT clones in response to transforming growth factor β (TGF-β), which is a well-characterized inducer of EMT. TGF-β caused growth arrest and loss of epithelial cell junctions in the HaCaT derivatives, but mesenchymal markers were not induced, suggesting a partial, but not complete EMT response. Inflammation induced by COX-2 has been proposed to be a key mechanism in EMT of benign cells. Corroborating this notion, COX-2 was induced only in benign, not in malignant HaCaT derivatives. Furthermore, in cells in which TGF-β caused COX-2 induction, migration was clearly augmented. The concept of treating cancer is changing from targeting solely the cancer cells to targeting the whole microenvironment. The results of this work emphasise the role of activated fibroblasts in cancer progression and that CAFs should also be taken into consideration in the treatment of cancer. The results from these studies suggests that nemosis could be used as a diagnostic tool to distinguish in vitro activated fibroblasts from tumour stroma and also in studying the paracrine signalling that is mediated to other cell types via soluble factors.

VEGF-C and angiopoietins in lymphangiogenesis

Angiogenesis and lymphangiogenesis occur during development as the result of tightly coordinated signalling programs to generate two hierarchically organised vascular systems. All tissues and organs are dependent on a functional blood vasculature for oxygen and nutrients, whereas the lymphatic vasculature functions to collect excess tissue fluid, passing it through lymph nodes for immune surveillance, and returning it to the blood circulation. Effectors that control developmental angiogenesis and lymphangiogenesis are also involved in pathological settings, and therefore potential targets for therapy. Vascular endothelial growth factor (VEGF) and angiopoietin (Ang) growth factors, signalling through endothelial VEGFR and Tie receptors, have been established as key regulators of angiogenic and lymphangiogenic processes in development and disease. In this study, we aimed to obtain a clearer understanding of the vascular effects of stimulation by VEGF-C, Ang1 and Ang2, all known to be involved in lymphangiogenesis. In cell culture models, we found that both intrinsic and microenvironmental regulatory mechanisms are involved in the regulation of endothelial cell phenotypes, and distinct responses to VEGF signalling are induced by specific receptor pathways in different endothelial cell types. Surprisingly, we also found that Ang1 induces sprouting lymphangiogenesis in vivo by a VEGFR-3 dependent mechanism, establishing Ang1 as a novel lymphangiogenic factor. Using inducible transgenic mouse models, we found that VEGF-C-induced lymphatic hyperplasia persisted independently of the growth factor, indicating that short pro-lymphangiogenic therapy could lead to lasting improvements in tissue oedema. While VEGF-C had blood vessel effects in embryos, no angiogenic side effects were observed in adult tissues. Furthermore, inducible transgenic expression of Ang2 during embryonic development confirmed Ang2 as an important regulator of lymphatic remodelling and mural cell contacts. The unexpected similarity of the lymphatic maturation defects caused by excess Ang2 to those observed in Ang2 deficient mice demonstrated that correct doses of Ang2 are crucial for the control of lymphatic development. Unlike Ang1, Ang2 did not induce lymphatic sprouting. Although Ang1 has been shown to be able to substitute for Ang2 during developmental lymphangiogenesis, their lymphatic effects are not identical. These findings further our understanding of the basic mechanisms of angiogenesis and lymphangiogenesis, important for the future development of targeted therapies for vascular diseases such as cancer, inflammation, lymphoedema and ischemia. VEGF-C and Ang1 especially emerged as promising candidates for pro-lymphangiogenic therapy.

Tropical dryland agroforestry on clay soils: : Analysis of systems based on Acacia senegal in the Blue Nile region, Sudan

Acacia senegal, the gum arabic producing tree, is the most important component in traditional dryland agroforestry systems in the Blue Nile region, Sudan. The aim of the present study was to provide new knowledge on the potential use of A. senegal in dryland agroforestry systems on clay soils, as well as information on tree/crop interaction, and on silvicultural and management tools, with consideration on system productivity, nutrient cycling and sustainability. Moreover, the aim was also to clarify the intra-specific variation in the performance of A. senegal and, specifically, the adaptation of trees of different origin to the clay soils of the Blue Nile region. In agroforestry systems established at the beginning of the study, tree and crop growth, water use, gum and crop yields, nutrient cycling and system performance were investigated for a period of four years (1999 to 2002). Trees were grown at 5 x 5 m and 10 x 10 m spacing alone or in mixture with sorghum or sesame; crops were also grown in sole culture. The symbiotic biological N2 fixation by A. senegal was estimated using the 15N natural abundance (δ15N) procedure in eight provenances collected from different environments and soil types of the gum arabic belt and grown in clay soil in the Blue Nile region. Balanites aegyptiaca (a non-legume) was used as a non-N-fixing reference tree species, so as to allow 15N-based estimates of the proportion of the nitrogen in trees derived from the atmosphere. In the planted acacia trees, measurements were made on shoot growth, water-use efficiency (as assessed by the δ13C method) and (starting from the third year) gum production. Carbon isotope ratios were obtained from the leaves and branch wood samples. The agroforestry system design caused no statistically significant variation in water use, but the variation was highly significant between years, and the highest water use occurred in the years with high rainfall. No statistically significant differences were found in sorghum or sesame yields when intercropping and sole crop systems were compared (yield averages were 1.54 and 1.54 ha-1 for sorghum and 0.36 and 0.42 t ha-1 for sesame in the intercropped and mono-crop plots, respectively). Thus, at an early stage of agroforestry system management, A. senegal had no detrimental effect on crop yield, but the pattern of resource capture by trees and crops may change as the system matures. Intercropping resulted in taller trees and larger basal and crown diameters as compared to the development of sole trees. It also resulted in a higher land equivalent ratio. When gum yields were analysed it was found that a significant positive relationship existed between the second gum picking and the total gum yield. The second gum picking seems to be a decisive factor in gum production and could be used as an indicator for the total gum yield in a particular year. In trees, the concentrations of N and P were higher in leaves and roots, whereas the levels of K were higher in stems, branches and roots. Soil organic matter, N, P and K contents were highest in the upper soil stratum. There was some indication that the P content slightly increased in the topsoil as the agroforestry plantations aged. At a stocking of 400 trees ha-1 (5 x 5 m spacing), A. senegal accumulated in the biomass a total of 18, 1.21, 7.8 and 972 kg ha-1of N, P, K and OC, respectively. Trees contributed ca. 217 and 1500 kg ha-1 of K and OC, respectively, to the top 25-cm of soil over the first four years of intercropping. Acacia provenances of clay plain origin showed considerable variation in seed weight. They also had the lowest average seed weight as compared to the sandy soil (western) provenances. At the experimental site in the clay soil region, the clay provenances were distinctly superior to the sand provenances in all traits studied but especially in basal diameter and crown width, thus reflecting their adaptation to the environment. Values of δ13C, indicating water use efficiency, were higher in the sand soil group as compared to the clay one, both in leaves and in branch wood. This suggests that the sand provenances (with an average value of -28.07 ) displayed conservative water use and high drought tolerance. Of the clay provenances, the local one (Bout) displayed a highly negative (-29.31 ) value, which indicates less conservative water use that resulted in high productivity at this particular clay-soil site. Water use thus appeared to correspond to the environmental conditions prevailing at the original locations for these provenances. Results suggest that A. senegal provenances from the clay part of the gum belt are adapted for a faster growth rate and higher biomass and gum productivity as compared to provenances from sand regions. A strong negative relationship was found between the per-tree gum yield and water use efficiency, as indicated by δ13C. The differences in water use and gum production were greater among provenance groups than within them, suggesting that selection among rather than within provenances would result in distinct genetic gain in gum yield. The relative δ15N values ( ) were higher in B. aegyptiaca than in the N2-fixing acacia provenances. The amount of Ndfa increased significantly with age in all provenances, indicating that A. senegal is a potentially efficient nitrogen fixer and has an important role in t agroforestry development. The total above-ground contribution of fixed N to foliage growth in 4-year-old A. senegal trees was highest in the Rahad sand-soil provenance (46.7 kg N ha-1) and lowest in the Mazmoom clay-soil provenance (28.7 kg N ha-1). This study represents the first use of the δ15N method for estimating the N input by A. senegal in the gum belt of Sudan. Key words: Acacia senegal, agroforestry, clay plain, δ13C, δ15N, gum arabic, nutrient cycling, Ndfa, Sorghum bicolor, Sesamum indicum

Lignin biosynthesis in Norway spruce: from a model system to the tree

Lignin is a hydrophobic polymer that is synthesised in the secondary cell walls of all vascular plants. It enables water conduction through the stem, supports the upright growth habit and protects against invading pathogens. In addition, lignin hinders the utilisation of the cellulosic cell walls of plants in pulp and paper industry and as forage. Lignin precursors are synthesised in the cytoplasm through the phenylpropanoid pathway, transported into the cell wall and oxidised by peroxidases or laccases to phenoxy radicals that couple to form the lignin polymer. This study was conducted to characterise the lignin biosynthetic pathway in Norway spruce (Picea abies (L.) Karst.). We focused on the less well-known polymerisation stage, to identify the enzymes and the regulatory mechanisms that are involved. Available data for lignin biosynthesis in gymnosperms is scarce and, for example, the latest improvements in precursor biosynthesis have only been verified in herbaceous plants. Therefore, we also wanted to study in detail the roles of individual gene family members during developmental and stress-induced lignification, using EST sequencing and real-time RT-PCR. We used, as a model, a Norway spruce tissue culture line that produces extracellular lignin into the culture medium, and showed that lignin polymerisation in the tissue culture depends on peroxidase activity. We identified in the culture medium a significant NADH oxidase activity that could generate H2O2 for peroxidases. Two basic culture medium peroxidases were shown to have high affinity to coniferyl alcohol. Conservation of the putative substrate-binding amino acids was observed when the spruce peroxidase sequences were compared with other peroxidases with high affinity to coniferyl alcohol. We also used different peroxidase fractions to produce synthetic in vitro lignins from coniferyl alcohol; however, the linkage pattern of the suspension culture lignin could not be reproduced in vitro with the purified peroxidases, nor with the full complement of culture medium proteins. This emphasised the importance of the precursor radical concentration in the reaction zone, which is controlled by the cells through the secretion of both the lignin precursors and the oxidative enzymes to the apoplast. In addition, we identified basic peroxidases that were reversibly bound to the lignin precipitate. They could be involved, for example, in the oxidation of polymeric lignin, which is required for polymer growth. The dibenzodioxocin substructure was used as a marker for polymer oxidation in the in vitro polymerisation studies, as it is a typical substructure in wood lignin and in the suspension culture lignin. Using immunolocalisation, we found the structure mainly in the S2+S3 layers of the secondary cell walls of Norway spruce tracheids. The structure was primarily formed during the late phases of lignification. Contrary to the earlier assumptions, it appears to be a terminal structure in the lignin macromolecule. Most lignin biosynthetic enzymes are encoded for by several genes, all of which may not participate in lignin biosynthesis. In order to identify the gene family members that are responsible for developmental lignification, ESTs were sequenced from the lignin-forming tissue culture and developing xylem of spruce. Expression of the identified lignin biosynthetic genes was studied using real-time RT-PCR. Candidate genes for developmental lignification were identified by a coordinated, high expression of certain genes within the gene families in all lignin-forming tissues. However, such coordinated expression was not found for peroxidase genes. We also studied stress-induced lignification either during compression wood formation by bending the stems or after Heterobasidion annosum infection. Based on gene expression profiles, stress-induced monolignol biosynthesis appeared similar to the developmental process, and only single PAL and C3H genes were specifically up-regulated by stress. On the contrary, the up-regulated peroxidase genes differed between developmental and stress-induced lignification, indicating specific responses.