Roles of forced nicotine exposure and Comt gene disruption in the development of addiction-related behavioural and neurochemical changes in mice

Activation of midbrain dopamine systems is thought to be critically involved in the addictive properties of abused substances. Drugs of abuse increase dopamine release in the nucleus accumbens and dorsal striatum, which are the target areas of mesolimbic and nigrostriatal dopamine pathways, respectively. Dopamine release in the nucleus accumbens is thought to mediate the attribution of incentive salience to rewards, and dorsal striatal dopamine release is involved in habit formation. In addition, changes in the function of prefrontal cortex (PFC), the target area of mesocortical dopamine pathway, may skew information processing and memory formation such that the addict pays an abnormal amount of attention to drug-related cues. In this study, we wanted to explore how long-term forced oral nicotine exposure or the lack of catechol-O-methyltransferase (COMT), one of the dopamine metabolizing enzymes, would affect the functioning of these pathways. We also wanted to find out how the forced nicotine exposure or the lack of COMT would affect the consumption of nicotine, alcohol, or cocaine. First, we studied the effect of forced chronic nicotine exposure on the sensitivity of dopamine D2-like autoreceptors in microdialysis and locomotor activity experiments. We found that the sensitivity of these receptors was unchanged after forced oral nicotine exposure, although an increase in the sensitivity was observed in mice treated with intermittent nicotine injections twice daily for 10 days. Thus, the effect of nicotine treatment on dopamine autoreceptor sensitivity depends on the route, frequency, and time course of drug administration. Second, we investigated whether the forced oral nicotine exposure would affect the reinforcing properties of nicotine injections. The chronic nicotine exposure did not significantly affect the development of conditioned place preference to nicotine. In the intravenous self-administration paradigm, however, the nicotine-exposed animals self-administered nicotine at a lower unit dose than the control animals, indicating that their sensitivity to the reinforcing effects of nicotine was enhanced. Next, we wanted to study whether the Comt gene knock-out animals would be a suitable model to study alcohol and cocaine consumption or addiction. Although previous work had shown male Comt knock-out mice to be less sensitive to the locomotor-activating effects of cocaine, the present study found that the lack of COMT did not affect the consumption of cocaine solutions or the development of cocaine-induced place preference. However, the present work did find that male Comt knock-out mice, but not female knock-out mice, consumed ethanol more avidly than their wild-type littermates. This finding suggests that COMT may be one of the factors, albeit not a primary one, contributing to the risk of alcoholism. Last, we explored the effect of COMT deficiency on dorsal striatal, accumbal, and prefrontal cortical dopamine metabolism under no-net-flux conditions and under levodopa load in freely-moving mice. The lack of COMT did not affect the extracellular dopamine concentrations under baseline conditions in any of the brain areas studied. In the prefrontal cortex, the dopamine levels remained high for a prolonged time after levodopa treatment in male, but not female, Comt knock-out mice. COMT deficiency induced accumulation of 3,4-dihydroxyphenylacetic acid, which increased further under levodopa load. Homovanillic acid was not detectable in Comt knock-out animals either under baseline conditions or after levodopa treatment. Taken together, the present results show that although forced chronic oral nicotine exposure affects the reinforcing properties of self-administered nicotine, it is not an addiction model itself. COMT seems to play a minor role in dopamine metabolism and in the development of addiction under baseline conditions, indicating that dopamine function in the brain is well-protected from perturbation. However, the role of COMT becomes more important when the dopaminergic system is challenged, such as by pharmacological manipulation.

Changing Lived Worlds of Contemporary Amazonian Native Young People : Manchineri Youths in the Reserve and the City, Brazil-Acre

This thesis discusses the contemporary construction of the lived worlds of indigenous Amazonian youths. Today’s native peoples are considerably affected by the processes of globalization and urbanization, which have led to new ways of relating to their cultural traditions. This work presents a case study of Manchineri youngsters aged between 14 and 24 years old living in Acre state in Brazilian Amazonia. The Arawak-speaking Manchineri number some 1,000 people; their legally demarcated reserve is situated next to the River Yaco. The research is based on ethnographic material collected in the Mamoadate reserve and in the state capital, Rio Branco. By comparing the youth in different physical and social environments (the reserve and the city), my attempt has been to search for the most typical elements maintained, altered and created in the current lived worlds of Manchineri youths. Fieldwork methods included interviews, participant observation, photographs, video recordings, and drawings. The material was analyzed within the multidisciplinary framework of the social and cultural construction of knowledge. The study applies the concepts of social field, symbolic capital, and habitus as they have been used by Pierre Bourdieu; perspective as developed recently in Amazonian ethnology; the sacred as a cultural category as understood in the study of religion; and individual and person as concepts central to anthropology and sociology. Additionally, the study can be contextualized within youth studies, Latin American studies, and urban studies. The results of the study show that the everyday lives of young Amazonian native people are formed by a complex mixture of ‘modernity’ and ‘tradition’, fragmentation, and transitions between different conceptual frameworks. Part II discusses the ethnographic material in depth and shows that indigenous adolescents act from a variety of social perspectives: the native youth’s own ethnic group, divided into sub-groups, especially into urban residents and those living in the reserve; ancestors, super-human agents and spirits; other indigenous groups and non-natives. Consequently, besides the traditional initiation ritual, we find various contemporary rites of passage to adulthood: state-education, learning traditional practices, shamanism, matrimony, and transitions between the reserve and urban areas. According to these results, new social roles, political organization, responsibilities, and in general the desire to be respected, require both ‘modern’ and ‘traditional’ abilities. In Part III, the study shows that the current power relations constituted by new social contacts, ethnic recognition, and cooperation with different institutions have resulted in the formation of new social fields: youth cultures, the ethnic group, shamanic practices, the ethnopolitical movement, and indigenous students. The capacity of young Amazonian Indians to act in contemporary social fields produces them as full persons. The study also argues that the elements of the lived worlds can be divided into these social fields. When focusing on these fields, it became evident that these comprise the strategies adopted by young Indians to break through social and cultural barriers.

A Literary Turn : Rethinking the Roles of Generalization and Theory in Anglo-American Moral Philosophy

This work investigates the role of narrative literature in late-20th century and contemporary Anglo-American moral philosophy. It aims to show the trend of reading narrative literature for purposes of moral philosophy from the 1970 s and early 80 s to the present day as a part of a larger movement in Anglo-American moral philosophy, and to present a view of its significance for moral philosophy overall. Chapter 1 provides some preliminaries concerning the view of narrative literature which my discussion builds on. In chapter 2 I give an outline of how narrative literature is considered in contemporary Anglo-American moral philosophy, and connect this use to the broad trend of neo-Aristotelian ethics in this context. In chapter 3 I connect the use of literature to the idea of the non-generalizability of moral perception and judgment, which is central to the neo-Aristotelian trend, as well as to a range of moral particularisms and anti-theoretical positions of late 20th century and contemporary ethics. The joint task of chapters 2 and 3 is to situate the trend of reading narrative literature for the purposes of moral philosophy in the present context of moral philosophy. In the following two chapters, 4 and 5, I move on from the particularizing power of narrative literature, which is emphasized by neo-Aristotelians and particularists alike, to a broader under-standing of the intellectual potential of narrative literature. In chapter 4 I argue that narrative literature has its own forms of generalization which are enriching for our understanding of the workings of ethical generalizations in philosophy. In chapter 5 I discuss Iris Murdoch s and Martha Nussbaum s respective ways of combining ethical generality and particularity in a philosophical framework where both systematic moral theory and narrative literature are taken seriously. In chapter 6 I analyse the controversy between contemporary anti-theoretical conceptions of ethics and Nussbaum s refutation of these. I present my suggestion for how the significance of the ethics/literature discussion for moral philosophy can be understood if one wants to overcome the limitations of both Nussbaum s theory-centred, equilibrium-seeking perspective, and the anti-theorists repudiation of theory. I call my position the inclusive approach .

Arkkitehti Aarne Ervin kaupunkisuunnittelu pääkaupunkiseudulla : Suomalaisen suurkaupungin kaavoitusta toisen maailmansodan jälkeen

The Modern City Planning of Architect Aarne Ervi in the Helsinki Metropolitan Area: The Planning of the Finnish Capital after the Second World War This study focuses on the city planning of architect Aarne Ervi (1910-1977) in the Helsinki metropolitan area, which includes the cities of Helsinki, Espoo, Kauniainen and Vantaa, from the 1940s to the end of the 1960s. Ervi succeeded in several major architectural competitions in Finland, acted as the main designer of the "New Town" of Tapiola and of the suburb of Vantaanpuisto in the metropolitan area, and worked as the first director of the city planning department of Helsinki from 1965-1969. This study belongs to the field of planning history in which the art historical study of architecture blends with the history of Finnish society. I examine architect Aarne Ervi and his city planning architecture through the concept of "modern". I link the theoretical literature of modernism in architecture and the modernization of society with historical documents and empirical archival research. I examine Ervi's professional career, the teamwork characteristic of his office, and the collegial community in which Ervi serves different vocational roles as an architect. The postwar development of planning legislation and of municipal and state planning organisations provides the necessary context for urban planning. I also discuss the municipal development of Espoo and Vantaa and the regionalization process that occured in Helsinki during the decades in question. The main results of this study relate to the collective and cooperative group nature of work in architectural design, to the introduction of an alternative approach to the question of modernism in Finnish architectural discourse, and to the post-war planning history of legislative and institutional organisations in Finland. Furthermore, the study includes new historical research about the city planning department of the city of Helsinki, the planning of Tapiola and Vantaanpuisto, and the operations of the main developers of these two suburban areas: the Asuntosäästäjät Society and the Asuntosäätiö Foundation.

Women, environmental changes and forestry-related development : Gender-affected roles of rural people in land degradation and environmental rehabilitation in a dry region of Sudan

The purpose of the present study was to increase understanding of the interaction of rural people and, specifically, women with the environment in a dry area in Sudan. The study that included both nomadic pastoralists and farmers aimed at answering two main research questions, namely: What kinds of roles have the local people, and the women in particular, had in land degradation in the study area and what kinds of issues would a gender-sensitive, forestry-related environmental rehabilitation intervention need to consider there? The study adopted the definition of land degradation as proposed by the United Nations Convention to Combat Desertification (UNCCD), which describes land degradation as reduction or loss the biological or economic productivity and complexity of land in arid, semi-arid and dry sub-humid areas. The Convention perceives desertification as land degradation. The dry study area in Sudan, South of the Sahara, has been the subject of land degradation or desertification discussions since the 1970s, and other studies have been also conducted to assess the degradation in the area. Nevertheless, the exact occurrence, scale and local significance of land degradation in the area is still unclear. This study explored how the rural population whose livelihood depended on the area, perceived environmental changes occurring there and compared their conceptions with other sources of information of the area such as research reports. The main fieldwork methods included interviews with open-ended questions and observation of people and the environment. The theoretical framework conceptualised the rural population as land users whose choices of environmental activities are affected by multiple factors in the social and biophysical contexts in which they live. It was emphasised that these factors have their own specific characteristics in different contexts, simultaneously recognising that there are also factors that generally affect environmental practices in various areas such as the land users' environmental literacy (conceptions of the environment), gender and livelihood needs. The people studied described that environmental changes, such as reduced vegetation cover and cropland production, had complicated the maintenance of their livelihoods in the study area. Some degraded sites were also identified through observations during the fieldwork. Whether a large-scale reduction of cropland productivity had occurred in the farmers' croplands remained, however, unclear. The study found that the environmental impact of the rural women's activities varied and was normally limited. The women's most significant environmental impact resulted from their cutting of trees, which was likely to contribute, at least in some places, to land degradation, affecting the environment together with climate and livestock. However, when a wider perspective is taken, it becomes questionable whether the women have really played roles in land degradation, since gender, poverty and the need to maintain livelihood had caused them to conduct environmentally harmful activities. The women have had, however, no power to change the causes of their activities. The findings further suggested that an inadequate availability of food was the most critical problem in the study area. Therefore, an environmental programme in the area was suggested to include technical measures to increase the productivity of croplands, opportunities for income generation and readiness to co-operate with other programmes to improve the local people's abilities to maintain their livelihoods. In order to protect the environment and alleviate the women's work burden, the introduction of fuel-saving stoves was also suggested. Furthermore, it was suggested that increased planting of trees on homesteads would be supported by an easy availability of tree seedlings. Planting trees on common property land was, however, perceived as extremely demanding in the study area, due to scarcity of such land. In addition, it became apparent that the local land users, and women in particular, needed to allocate their labour to maintain the immediate livelihood of their families and were not motivated to allocate their labour solely for environmental rehabilitation. Nonetheless, from the point of view of the existing social structures, women's active participation in a community-based environmental programme would be rather natural, particularly among the farmer women who had already formed a women's group and participated in communal decision making. Forming of a women group or groups was suggested to further support both the farmer women's and pastoral women's active participation within an environmental programme and their general empowerment. An Environmental programme would need to acknowledge that improving rural people's well-being and maintaining their livelihood in the study area requires development and co-operation with various sectors in Sudan.

What was behind the bark? : An assessment of decay among urban Tilia, Betula and Acer trees felled as hazardous in the Helsinki City area

Old trees growing in urban environments are often felled due to symptoms of mechanical defects that could be hazardous to people and property. The decisions concerning these removals are justified by risk assessments carried out by tree care professionals. The major motivation for this study was to determine the most common profiles of potential hazard characteristics for the three most common urban tree genera in Helsinki City: Tilia, Betula and Acer, and in this way improve management practices and protection of old amenity trees. For this research, material from approximately 250 urban trees was collected in cooperation with the City of Helsinki Public Works Department during 2001 - 2004. From the total number of trees sampled, approximately 70% were defined as hazardous. The tree species had characteristic features as potential hazard profiles. For Tilia trees, hollowed heartwood with low fungal activity and advanced decay caused by Ganoderma lipsiense were the two most common profiles. In Betula spp., the primary reason for tree removal was usually lowered amenity value in terms of decline of the crown. Internal cracks, most often due to weak fork formation, were common causes of potential failure in Acer spp. Decay caused by Rigidoporus populinus often increased the risk of stem breakage in these Acer trees. Of the decay fungi observed, G. lipsiense was most often the reason for the increased risk of stem collapse. Other fungi that also caused extensive decay were R. populinus, Inonotus obliquus, Kretzschmaria deusta and Phellinus igniarius. The most common decay fungi in terms of incidence were Pholiota spp., but decay caused by these species did not have a high potential for causing stem breakage, because it rarely extended to the cambium. The various evaluations used in the study suggested contradictions in felling decisions based on trees displaying different stages of decay. For protection of old urban trees, it is crucial to develop monitoring methods so that tree care professionals could better analyse the rate of decay progression towards the sapwood and separate those trees with decreasing amounts of sound wood from those with decay that is restricted to the heartwood area.

Urban energy fluxes in Helsinki and their high frequency spectral corrections

Inadvertent climate modification has led to an increase in urban temperatures compared to the surrounding rural area. The main reason for the temperature rise is the altered energy portioning of input net radiation to heat storage and sensible and latent heat fluxes in addition to the anthropogenic heat flux. The heat storage flux and anthropogenic heat flux have not yet been determined for Helsinki and they are not directly measurable. To the contrary, turbulent fluxes of sensible and latent heat in addition to net radiation can be measured, and the anthropogenic heat flux together with the heat storage flux can be solved as a residual. As a result, all inaccuracies in the determination of the energy balance components propagate to the residual term and special attention must be paid to the accurate determination of the components. One cause of error in the turbulent fluxes is the fluctuation attenuation at high frequencies which can be accounted for by high frequency spectral corrections. The aim of this study is twofold: to assess the relevance of high frequency corrections to water vapor fluxes and to assess the temporal variation of the energy fluxes. Turbulent fluxes of sensible and latent heat have been measured at SMEAR III station, Helsinki, since December 2005 using the eddy covariance technique. In addition, net radiation measurements have been ongoing since July 2007. The used calculation methods in this study consist of widely accepted eddy covariance data post processing methods in addition to Fourier and wavelet analysis. The high frequency spectral correction using the traditional transfer function method is highly dependent on relative humidity and has an 11% effect on the latent heat flux. This method is based on an assumption of spectral similarity which is shown not to be valid. A new correction method using wavelet analysis is thus initialized and it seems to account for the high frequency variation deficit. Anyhow, the resulting wavelet correction remains minimal in contrast to the traditional transfer function correction. The energy fluxes exhibit a behavior characteristic for urban environments: the energy input is channeled to sensible heat as latent heat flux is restricted by water availability. The monthly mean residual of the energy balance ranges from 30 Wm-2 in summer to -35 Wm-2 in winter meaning a heat storage to the ground during summer. Furthermore, the anthropogenic heat flux is approximated to be 50 Wm-2 during winter when residential heating is important.

Chemical and source characterisation of size-segregated urban air particulate matter

Recent epidemiological studies have shown a consistent association of the mass concentration of urban air thoracic (PM10) and fine (PM2.5) particles with mortality and morbidity among cardiorespiratory patients. However, the chemical characteristics of different particulate size ranges and the biological mechanisms responsible for these adverse health effects are not well known. The principal aims of this thesis were to validate a high volume cascade impactor (HVCI) for the collection of particulate matter for physicochemical and toxicological studies, and to make an in-depth chemical and source characterisation of samples collected during different pollution situations. The particulate samples were collected with the HVCI, virtual impactors and a Berner low pressure impactor in six European cities: Helsinki, Duisburg, Prague, Amsterdam, Barcelona and Athens. The samples were analysed for particle mass, common ions, total and water-soluble elements as well as elemental and organic carbon. Laboratory calibration and field comparisons indicated that the HVCI can provide a unique large capacity, high efficiency sampling of size-segregated aerosol particles. The cutoff sizes of the recommended HVCI configuration were 2.4, 0.9 and 0.2 μm. The HVCI mass concentrations were in a good agreement with the reference methods, but the chemical composition of especially the fine particulate samples showed some differences. This implies that the chemical characterization of the exposure variable in toxicological studies needs to be done from the same HVCI samples as used in cell and animal studies. The data from parallel, low volume reference samplers provide valuable additional information for chemical mass closure and source assessment. The major components of PM2.5 in the virtual impactor samples were carbonaceous compounds, secondary inorganic ions and sea salt, whereas those of coarse particles (PM2.5-10) were soil-derived compounds, carbonaceous compounds, sea salt and nitrate. The major and minor components together accounted for 77-106% and 77-96% of the gravimetrically-measured masses of fine and coarse particles, respectively. Relatively large differences between sampling campaigns were observed in the organic carbon content of the PM2.5 samples as well as the mineral composition of the PM2.5-10 samples. A source assessment based on chemical tracers suggested clear differences in the dominant sources (e.g. traffic, residential heating with solid fuels, metal industry plants, regional or long-range transport) between the sampling campaigns. In summary, the field campaigns exhibited different profiles with regard to particulate sources, size distribution and chemical composition, thus, providing a highly useful setup for toxicological studies on the size-segregated HVCI samples.

Controls on trace metals in urban stream sediments : implications for pollution monitoring using sediment chemistry data

Contamination of urban streams is a rising topic worldwide, but the assessment and investigation of stormwater induced contamination is limited by the high amount of water quality data needed to obtain reliable results. In this study, stream bed sediments were studied to determine their contamination degree and their applicability in monitoring aquatic metal contamination in urban areas. The interpretation of sedimentary metal concentrations is, however, not straightforward, since the concentrations commonly show spatial and temporal variations as a response to natural processes. The variations of and controls on metal concentrations were examined at different scales to increase the understanding of the usefulness of sediment metal concentrations in detecting anthropogenic metal contamination patterns. The acid extractable concentrations of Zn, Cu, Pb and Cd were determined from the surface sediments and water of small streams in the Helsinki Metropolitan region, southern Finland. The data consists of two datasets: sediment samples from 53 sites located in the catchment of the Stream Gräsanoja and sediment and water samples from 67 independent catchments scattered around the metropolitan region. Moreover, the sediment samples were analyzed for their physical and chemical composition (e.g. total organic carbon, clay-%, Al, Li, Fe, Mn) and the speciation of metals (in the dataset of the Stream Gräsanoja). The metal concentrations revealed that the stream sediments were moderately contaminated and caused no immediate threat to the biota. However, at some sites the sediments appeared to be polluted with Cu or Zn. The metal concentrations increased with increasing intensity of urbanization, but site specific factors, such as point sources, were responsible for the occurrence of the highest metal concentrations. The sediment analyses revealed, thus a need for more detailed studies on the processes and factors that cause the hot spot metal concentrations. The sediment composition and metal speciation analyses indicated that organic matter is a very strong indirect control on metal concentrations, and it should be accounted for when studying anthropogenic metal contamination patterns. The fine-scale spatial and temporal variations of metal concentrations were low enough to allow meaningful interpretation of substantial metal concentration differences between sites. Furthermore, the metal concentrations in the stream bed sediments were correlated with the urbanization of the catchment better than the total metal concentrations in the water phase. These results suggest that stream sediments show true potential for wider use in detecting the spatial differences in metal contamination of urban streams. Consequently, using the sediment approach regional estimates of the stormwater related metal contamination could be obtained fairly cost-effectively, and the stability and reliability of results would be higher compared to analyses of single water samples. Nevertheless, water samples are essential in analysing the dissolved concentrations of metals, momentary discharges from point sources in particular.

Middleware for Mobile Sensing Applications in Urban Environments

Sensor networks represent an attractive tool to observe the physical world. Networks of tiny sensors can be used to detect a fire in a forest, to monitor the level of pollution in a river, or to check on the structural integrity of a bridge. Application-specific deployments of static-sensor networks have been widely investigated. Commonly, these networks involve a centralized data-collection point and no sharing of data outside the organization that owns it. Although this approach can accommodate many application scenarios, it significantly deviates from the pervasive computing vision of ubiquitous sensing where user applications seamlessly access anytime, anywhere data produced by sensors embedded in the surroundings. With the ubiquity and ever-increasing capabilities of mobile devices, urban environments can help give substance to the ubiquitous sensing vision through Urbanets, spontaneously created urban networks. Urbanets consist of mobile multi-sensor devices, such as smart phones and vehicular systems, public sensor networks deployed by municipalities, and individual sensors incorporated in buildings, roads, or daily artifacts. My thesis is that "multi-sensor mobile devices can be successfully programmed to become the underpinning elements of an open, infrastructure-less, distributed sensing platform that can bring sensor data out of their traditional close-loop networks into everyday urban applications". Urbanets can support a variety of services ranging from emergency and surveillance to tourist guidance and entertainment. For instance, cars can be used to provide traffic information services to alert drivers to upcoming traffic jams, and phones to provide shopping recommender services to inform users of special offers at the mall. Urbanets cannot be programmed using traditional distributed computing models, which assume underlying networks with functionally homogeneous nodes, stable configurations, and known delays. Conversely, Urbanets have functionally heterogeneous nodes, volatile configurations, and unknown delays. Instead, solutions developed for sensor networks and mobile ad hoc networks can be leveraged to provide novel architectures that address Urbanet-specific requirements, while providing useful abstractions that hide the network complexity from the programmer. This dissertation presents two middleware architectures that can support mobile sensing applications in Urbanets. Contory offers a declarative programming model that views Urbanets as a distributed sensor database and exposes an SQL-like interface to developers. Context-aware Migratory Services provides a client-server paradigm, where services are capable of migrating to different nodes in the network in order to maintain a continuous and semantically correct interaction with clients. Compared to previous approaches to supporting mobile sensing urban applications, our architectures are entirely distributed and do not assume constant availability of Internet connectivity. In addition, they allow on-demand collection of sensor data with the accuracy and at the frequency required by every application. These architectures have been implemented in Java and tested on smart phones. They have proved successful in supporting several prototype applications and experimental results obtained in ad hoc networks of phones have demonstrated their feasibility with reasonable performance in terms of latency, memory, and energy consumption.

Use of ecological information in urban planning

Urbanization leads to irreversible land-use change, which has ecological consequences such as the loss and fragmentation of green areas, and structural and functional changes in terrestrial and aquatic ecosystems. These consequences diminish ecosystem services important for human populations living in urban areas. All this results in a conflict situation: how to simultaneously meet the needs of city growth and the principles of sustainable development, and especially conserve important green areas within and around built-up areas? Urban planners and decisionmakers have an important role in this, since they must use the ecological information mainly from species and biotope inventories and biodiversity impact assessments in determining the conservation values of green areas. The main aim of this thesis was to study the use of ecological information in the urban land-use planning and decisionmaking process in the Helsinki Metropolitan Area, Finland. At first, the literature on ecological-social systems linkages related to urban planning was reviewed. Based on the review, a theoretical and conceptual framework for the research on Finnish urban setting was adapted. Secondly, factors determining the importance and effectiveness of incorporation of ecological information into the urban planning process, and the challenges related to the use of ecological information were studied. Thirdly, the importance and use of Local Ecological Knowledge in urban planning were investigated. Then, factors determining the consideration of urban green areas and related ecological information in political land-use decisionmaking were studied. Finally, in a case study illustrating the above considerations, the importance of urban stream ecosystems in the land-use planning was investigated. This thesis demonstrated that although there are several challenges in using ecological information effectively, it is considered as an increasingly important part of the basic information used in urban planning and decisionmaking process. The basic determinants for this are the recent changes in environmental legislation, but also the increasing appreciation of green areas and their conservation values by all the stakeholders. In addition, Local Ecological Knowledge in its several forms can be a source of ecological information for planners if incorporated effectively into the process. This study also showed that rare or endangered species and biotopes, and related ecological information receive priority in the urban planning process and usually pass through the decisionmaking system. Furthermore, the stream Rekolanoja case indicates that planners and residents see the value of urban stream ecosystem as increasingly important for the local health and social values, such as recreation and stress relief.

Bending the Rules of Cell Protrusions : Molecular Mechanisms and Biological Roles of Inverse-BAR Proteins in Cell Morphogenesis

Plasma membrane adopts myriad of different shapes to carry out essential cellular processes such as nutrient uptake, immunological defence mechanisms and cell migration. Therefore, the details how different plasma membrane structures are made and remodelled are of the upmost importance. Bending of plasma membrane into different shapes requires substantial amount of force, which can be provided by the actin cytoskeleton, however, the molecules that regulate the interplay between the actin cytoskeleton and plasma membrane have remained elusive. Recent findings have placed new types of effectors at sites of plasma membrane remodelling, including BAR proteins, which can directly bind and deform plasma membrane into different shapes. In addition to their membrane-bending abilities, BAR proteins also harbor protein domains that intimately link them to the actin cytoskeleton. The ancient BAR domain fold has evolved into at least three structurally and functionally different sub-groups: the BAR, F-BAR and I-BAR domains. This thesis work describes the discovery and functional characterization of the Inverse-BAR domains (I-BARs). Using synthetic model membranes, we have shown that I-BAR domains bind and deform membranes into tubular structures through a binding-surface composed of positively charged amino acids. Importantly, the membrane-binding surface of I-BAR domains displays an inverse geometry to that of the BAR and F-BAR domains, and these structural differences explain why I-BAR domains induce cell protrusions whereas BAR and most F-BAR domains induce cell invaginations. In addition, our results indicate that the binding of I-BAR domains to membranes can alter the spatial organization of phosphoinositides within membranes. Intriguingly, we also found that some I-BAR domains can insert helical motifs into the membrane bilayer, which has important consequences for their membrane binding/bending functions. In mammals there are five I-BAR domain containing proteins. Cell biological studies on ABBA revealed that it is highly expressed in radial glial cells during the development of the central nervous system and plays an important role in the extension process of radial glia-like C6R cells by regulating lamellipodial dynamics through its I-BAR domain. To reveal the role of these proteins in the context of animals, we analyzed MIM knockout mice and found that MIM is required for proper renal functions in adult mice. MIM deficient mice displayed a severe urine concentration defect due to defective intercellular junctions of the kidney epithelia. Consistently, MIM localized to adherens junctions in cultured kidney epithelial cells, where it promoted actin assembly through its I-BAR andWH2 domains. In summary, this thesis describes the mechanism how I-BAR proteins deform membranes and provides information about the biological role of these proteins, which to our knowledge are the first proteins that have been shown to directly deform plasma membrane to make cell protrusions.