The role of cyclase-associated protein (CAP) in actin dynamics during cell motility and morphogenesis

The highly dynamic remodeling of the actin cytoskeleton is responsible for most motile and morphogenetic processes in all eukaryotic cells. In order to generate appropriate spatial and temporal movements, the actin dynamics must be under tight control of an array of actin binding proteins (ABPs). Many proteins have been shown to play a specific role in actin filament growth or disassembly of older filaments. Very little is known about the proteins affecting recycling i.e. the step where newly depolymerized actin monomers are funneled into new rounds of filament assembly. A central protein family involved in the regulation of actin turnover is cyclase-associated proteins (CAP, called Srv2 in budding yeast). This 50-60 kDa protein was first identified from yeast as a suppressor of an activated RAS-allele and a factor associated with adenylyl cyclase. The CAP proteins harbor N-terminal coiled-coil (cc) domain, originally identified as a site for adenylyl cyclase binding. In the N-terminal half is also a 14-3-3 like domain, which is followed by central proline-rich domains and the WH2 domain. In the C-terminal end locates the highly conserved ADP-G-actin binding domain. In this study, we identified two previously suggested but poorly characterized interaction partners for Srv2/CAP: profilin and ADF/cofilin. Profilins are small proteins (12-16 kDa) that bind ATP-actin monomers and promote the nucleotide exchange of actin. The profilin-ATP-actin complex can be directly targeted to the growth of the filament barbed ends capped by Ena/VASP or formins. ADF/cofilins are also small (13-19 kDa) and highly conserved actin binding proteins. They depolymerize ADP-actin monomers from filament pointed ends and remain bound to ADP-actin strongly inhibiting nucleotide exchange. We revealed that the ADP-actin-cofilin complex is able to directly interact with the 14-3-3 like domain at the N-terminal region of Srv2/CAP. The C-terminal high affinity ADP-actin binding site of Srv2/CAP competes with cofilin for an actin monomer. Cofilin can thus be released from Srv2/CAP for the subsequent round of depolymerization. We also revealed that profilin interacts with the first proline-rich region of Srv2/CAP and that the binding occurs simultaneously with ADP-actin binding to C-terminal domain of Srv2/CAP. Both profilin and Srv2/CAP can promote nucleotide exchange of actin monomer. Because profilin has much higher affinity to ATP-actin than Srv2/CAP, the ATP-actin-profilin complex is released for filament polymerization. While a disruption of cofilin binding in yeast Srv2/CAP produces a severe phenotype comparable to Srv2/CAP deletion, an impairment of profilin binding from Srv2/CAP results in much milder phenotype. This suggests that the interaction with cofilin is essential for the function of Srv2/CAP, whereas profilin can also promote its function without direct interaction with Srv2/CAP. We also show that two CAP isoforms with specific expression patterns are present in mice. CAP1 is the major isoform in most tissues, while CAP2 is predominantly expressed in muscles. Deletion of CAP1 from non-muscle cells results in severe actin phenotype accompanied with mislocalization of cofilin to cytoplasmic aggregates. Together these studies suggest that Srv2/CAP recycles actin monomers from cofilin to profilin and thus it plays a central role in actin dynamics in both yeast and mammalian cells.

Invertebrate predation and trophic cascades in a pelagic food web : The multiple roles of Chaoborus flavicans (Meigen) in a clay-turbid lake

In lake ecosystems, both fish and invertebrate predators have dramatic effects on their prey communities. Fish predation selects large cladocerans while invertebrate predators prefer prey of smaller size. Since invertebrate predators are the preferred food items for fish, their occurrence at high densities is often connected with the absence or low number of fish. It is generally believed that invertebrate predators can play a significant role only if the density of planktivorous fish is low. However, in eutrophic clay-turbid Lake Hiidenvesi (southern Finland), a dense population of predatory Chaoborus flavicans larvae coexists with an abundant fish population. The population covers the stratifying area of the lake and attains a maximum population density of 23000 ind. m-2. This thesis aims to clarify the effects of Chaoborus flavicans on the zooplankton community and the environmental factors facilitating the coexistence of fish and invertebrate predators. In the stratifying area of Lake Hiidenvesi, the seasonal succession of cladocerans was exceptional. The spring biomass peak of cladocerans was missing and the highest biomass occurred in midsummer. In early summer, the consumption rate by chaoborids clearly exceeded the production rate of cladocerans and each year the biomass peak of cladocerans coincided with the minimum chaoborid density. In contrast, consumption by fish was very low and each study year cladocerans attained maximum biomass simultaneously with the highest consumption by smelt (Osmerus eperlanus). The results indicated that Chaoborus flavicans was the main predator of cladocerans in the stratifying area of Lake Hiidenvesi. The clay turbidity strongly contributed to the coexistence of chaoborids and smelt at high densities. Turbidity exceeding 30 NTU combined with light intensity below 0.1 μE m-2 s-1provides an efficient daytime refuge for chaoborids, but turbidity alone is not an adequate refuge unless combined with low light intensity. In the non-stratifying shallow basins of Lake Hiidenvesi, light intensity exceeds this level during summer days at the bottom of the lake, preventing Chaoborus forming a dense population in the shallow parts of the lake. Chaoborus can be successful particularly in deep, clay-turbid lakes where they can remain high in the water column close to their epilimnetic prey. Suspended clay alters the trophic interactions by weakening the link between fish and Chaoborus, which in turn strengthens the effect of Chaoborus predation on crustacean zooplankton. Since food web management largely relies on manipulations of fish stocks and the cascading effects of such actions, the validity of the method in deep clay-turbid lakes may be questioned.

Genetic background of bipolar disorder and related cognitive impairments

Bipolar disorder (BP) is a complex psychiatric disorder characterized by episodes of mania and depression. BP affects approximately 1% of the world’s population and shows no difference in lifetime prevalence between males and females. BP arises from complex interactions among genetic, developmental and environmental factors, and it is likely that several predisposing genes are involved in BP. The genetic background of BP is still poorly understood, although intensive and long-lasting research has identified several chromosomal regions and genes involved in susceptibility to BP. This thesis work aims to identify the genetic variants that influence bipolar disorder in the Finnish population by candidate gene and genome-wide linkage analyses in families with many BP cases. In addition to diagnosis-based phenotypes, neuropsychological traits that can be seen as potential endophenotypes or intermediate traits for BP were analyzed. In the first part of the thesis, we examined the role of the allelic variants of the TSNAX/DISC1 gene cluster to psychotic and bipolar spectrum disorders and found association of distinct allelic haplotypes with these two groups of disorders. The haplotype at the 5’ end of the Disrupted-in-Schizophrenia-1 gene (DISC1) was over-transmitted to males with psychotic disorder (p = 0.008; for an extended haplotype p = 0.0007 with both genders), whereas haplotypes at the 3’ end of DISC1 associated with bipolar spectrum disorder (p = 0.0002; for an extended haplotype p = 0.0001). The variants of these haplotypes also showed association with different cognitive traits. The haplotypes at the 5’ end associated with perseverations and auditory attention, while the variants at the 3’ end associated with several cognitive traits including verbal fluency and psychomotor processing speed. Second, in our complete set of BP families with 723 individuals we studied six functional candidate genes from three distinct signalling systems: serotonin-related genes (SLC6A4 and TPH2), BDNF -related genes (BDNF, CREB1 and NTRK2) and one gene related to the inflammation and cytokine system (P2RX7). We replicated association of the functional variant Val66Met of BDNF with BP and better performance in retention. The variants at the 5’ end of SLC6A4 also showed some evidence of association among males (p = 0.004), but the widely studied functional variants did not yield any significant results. A protective four-variant haplotype on P2RX7 showed evidence of association with BP and executive functions: semantic and phonemic fluency (p = 0.006 and p = 0.0003, respectively). Third, we analyzed 23 bipolar families originating from the North-Eastern region of Finland. A genome-wide scan was performed using the 6K single nucleotide polymorphism (SNP) array. We identified susceptibility loci at chromosomes 7q31 with a LOD score of 3.20 and at 9p13.1 with a LOD score of 4.02. We followed up both linkage findings in the complete set of 179 Finnish bipolar families. The finding on chromosome 9p13 was supported (maximum LOD score of 3.02), but the susceptibility gene itself remains unclarified. In the fourth part of the thesis, we wanted to test the role of the allelic variants that have associated with bipolar disorder in recent genome-wide association studies (GWAS). We could confirm findings for the DFNB31, SORCS2, SCL39A3, and DGKH genes. The best signal in this study comes from DFNB31, which remained significant after multiple testing corrections. Two variants of SORCS2 were allelic replications and presented the same signal as the haplotype analysis. However, no association was detected with the PALB2 gene, which was the most significantly associated region in the previous GWAS. Our results indicate that BP is heterogeneous and its genetic background may accordingly vary in different populations. In order to fully understand the allelic heterogeneity that underlies common diseases such as BP, complete genome sequencing for many individuals with and without the disease is required. Identification of the specific risk variants will help us better understand the pathophysiology underlying BP and will lead to the development of treatments with specific biochemical targets. In addition, it will further facilitate the identification of environmental factors that alter risk, which will potentially provide improved occupational, social and psychological advice for individuals with high risk of BP.

Bone Stress Injuries of the Foot and Ankle

Bone stress injuries of the foot have been known for more than 150 years. For a century, their primary diagnostic imaging tool has been radiography. However, currently the golden standard for establishing the diagnosis of stress injuries is magnetic resonance imaging (MRI). Although the injury type has been fairly well documented in the earlier literature, little information is available on the healing of stress injuries located in e.g. the talus and calcaneus. The current study retrospectively evaluated the stress injuries of the foot and ankle treated at the Central Military Hospital over a period of eight years in patients who underwent MRI for stress injury of the foot. The imaging studies of the patients were reevaluated to determine the exact nature of the stress injury. Moreover, the hospital records of the patients were reviewed to determine the healing of stress injuries of the talus and calcaneus. Patients with a stress fracture in the talus were recalled for a follow-up examination and MRI scan one to six years after the initial injury to determine if the fracture had completely healed, clinically and radiologically. The bone stress injuries of the foot were found to affect more than one bone in a majority of the cases. The talus and the calcaneus were the bones most commonly affected. In the talus, the most common site for the injuries was the head of the bone, and in the calcaneus, the posterior part of the bone. The injuries in these bones were associated with injuries in the surrounding bones. Stress injuries in the calcaneus seemed to heal well. No complications were seen in the primary healing process. The patients were, however, sometimes compelled to refrain from physical training for up to months. In the talus, minor degenerative findings of the articular surface were seen in half of the patients who participated in a follow-up MRI scan and radiographs taken one to six years after the initial injury. Half of the patients also reported minor exercise related symptoms in the follow-up. The symptoms were, however, not noticeable in everyday life.

Studies of Earth Dynamics with the Superconducting Gravimeter

The superconducting (or cryogenic) gravimeter (SG) is based on the levitation of a super­conducting sphere in a stable magnetic field created by current in superconducting coils. Depending on frequency, it is capable of detecting gravity variations as small as 10-11ms-2. For a single event, the detection threshold is higher, conservatively about 10-9 ms-2. Due to its high sensitivity and low drift rate, the SG is eminently suitable for the study of geodynamical phenomena through their gravity signatures. I present investigations of Earth dynamics with the superconducting gravimeter GWR T020 at Metsähovi from 1994 to 2005. The history and key technical details of the installation are given. The data processing methods and the development of the local tidal model at Metsähovi are presented. The T020 is a part of the worldwide GGP (Global Geodynamics Project) network, which consist of 20 working station. The data of the T020 and of other participating SGs are available to the scientific community. The SG T020 have used as a long-period seismometer to study microseismicity and the Earth s free oscillation. The annual variation, spectral distribution, amplitude and the sources of microseism at Metsähovi were presented. Free oscillations excited by three large earthquakes were analyzed: the spectra, attenuation and rotational splitting of the modes. The lowest modes of all different oscillation types are studied, i.e. the radial mode 0S0, the "football mode" 0S2, and the toroidal mode 0T2. The very low level (0.01 nms-1) incessant excitation of the Earth s free oscillation was detected with the T020. The recovery of global and regional variations in gravity with the SG requires the modelling of local gravity effects. The most important of them is hydrology. The variation in the groundwater level at Metsähovi as measured in a borehole in the fractured bedrock correlates significantly (0.79) with gravity. The influence of local precipitation, soil moisture and snow cover are detectable in the gravity record. The gravity effect of the variation in atmospheric mass and that of the non-tidal loading by the Baltic Sea were investigated together, as sea level and air pressure are correlated. Using Green s functions it was calculated that a 1 metre uniform layer of water in the Baltic Sea increases the gravity at Metsähovi by 31 nms-2 and the vertical deformation is -11 mm. The regression coefficient for sea level is 27 nms-2m-1, which is 87% of the uniform model. These studies are associated with temporal height variations using the GPS data of Metsähovi permanent station. Results of long time series at Metsähovi demonstrated high quality of data and correctly carried out offsets and drift corrections. The superconducting gravimeter T020 has been proved to be an eminent and versatile tool in studies of the Earth dynamics.

Irradiation-mediated tailoring of carbon nanotubes

The ever-increasing demand for faster computers in various areas, ranging from entertaining electronics to computational science, is pushing the semiconductor industry towards its limits on decreasing the sizes of electronic devices based on conventional materials. According to the famous law by Gordon E. Moore, a co-founder of the world s largest semiconductor company Intel, the transistor sizes should decrease to the atomic level during the next few decades to maintain the present rate of increase in the computational power. As leakage currents become a problem for traditional silicon-based devices already at sizes in the nanometer scale, an approach other than further miniaturization is needed to accomplish the needs of the future electronics. A relatively recently proposed possibility for further progress in electronics is to replace silicon with carbon, another element from the same group in the periodic table. Carbon is an especially interesting material for nanometer-sized devices because it forms naturally different nanostructures. Furthermore, some of these structures have unique properties. The most widely suggested allotrope of carbon to be used for electronics is a tubular molecule having an atomic structure resembling that of graphite. These carbon nanotubes are popular both among scientists and in industry because of a wide list of exciting properties. For example, carbon nanotubes are electronically unique and have uncommonly high strength versus mass ratio, which have resulted in a multitude of proposed applications in several fields. In fact, due to some remaining difficulties regarding large-scale production of nanotube-based electronic devices, fields other than electronics have been faster to develop profitable nanotube applications. In this thesis, the possibility of using low-energy ion irradiation to ease the route towards nanotube applications is studied through atomistic simulations on different levels of theory. Specifically, molecular dynamic simulations with analytical interaction models are used to follow the irradiation process of nanotubes to introduce different impurity atoms into these structures, in order to gain control on their electronic character. Ion irradiation is shown to be a very efficient method to replace carbon atoms with boron or nitrogen impurities in single-walled nanotubes. Furthermore, potassium irradiation of multi-walled and fullerene-filled nanotubes is demonstrated to result in small potassium clusters in the hollow parts of these structures. Molecular dynamic simulations are further used to give an example on using irradiation to improve contacts between a nanotube and a silicon substrate. Methods based on the density-functional theory are used to gain insight on the defect structures inevitably created during the irradiation. Finally, a new simulation code utilizing the kinetic Monte Carlo method is introduced to follow the time evolution of irradiation-induced defects on carbon nanotubes on macroscopic time scales. Overall, the molecular dynamic simulations presented in this thesis show that ion irradiation is a promisingmethod for tailoring the nanotube properties in a controlled manner. The calculations made with density-functional-theory based methods indicate that it is energetically favorable for even relatively large defects to transform to keep the atomic configuration as close to the pristine nanotube as possible. The kinetic Monte Carlo studies reveal that elevated temperatures during the processing enhance the self-healing of nanotubes significantly, ensuring low defect concentrations after the treatment with energetic ions. Thereby, nanotubes can retain their desired properties also after the irradiation. Throughout the thesis, atomistic simulations combining different levels of theory are demonstrated to be an important tool for determining the optimal conditions for irradiation experiments, because the atomic-scale processes at short time scales are extremely difficult to study by any other means.

KAUPPAKESKUS OSANA KESTÄVÄÄ KAUPUNKIRAKENNETTA - Kauppakeskustoimijoiden näkemyksiä kauppakeskusten sijoittumisen kestävyydestä

The location and location guidance of shopping centers has been under much public discussion in Finland in the recent years. The Ministry of the Environment has expressed concern over the sustainability of ‘out-of-town’ shopping centers. Shopping centers outside the urban form are seen to cause more traffic, thus contributing to climate change by increasing carbon dioxide emissions. The sustainability of urban form has been researched in several studies and factors like urban density, public transport and a comfortable living environment were found to be the most important. This study presents the views of Finnish shopping center stakeholders on the sustainability of shopping center locations. These views were gathered using focus groups. Stakeholders included managers, consultants, investors, developers, architects and tenants of shopping centers and public sector actors dealing with shopping industry. As one theme in the discussions, participants were asked to present their views on the sustainability of shopping centers’ current locations. The study is part of the Aalto University of Technology KOKKKA project, which has its main focus upon shopping centers and sustainability. Shopping centers were seen to affect sustainability mainly through their location. A sustainable location was thought of as one that involved locating in an economically successful place, inside the urban form. A sustainable location was also easily accessible, with good access via public transport and the shopping center also had to create comfortable living environment in its surroundings. The views of the focus groups participants are similar to the views in sustainable urban structure theories and, inter alia, Finland’s national sustainable development strategy.

Valkoinen läiskä kartalla : Perusvärinnimet ja niiden merkityskentät unkarin- ja suomenkielisissä idiomeissa

Työni tavoitteena on vertailla unkarilaisia ja suomalaisia idiomeja, joissa esiintyy jokin perusvärinnimi. Perusvärinnimiä ovat fehér (valkoinen), fekete (musta), szürke (harmaa), piros tai vörös (punainen), zöld (vihreä), sárga (keltainen), kék (sininen) ja barna (ruskea). Erityisesti pyrin ottamaan selvää käytetäänkö samaa värinnimeä molemmissa kielissä samasta asiasta vai onko värinnimien käytössä tarkasteltujen kielten välillä eroja. Vertailen unkarilaisia idiomeja suomalaisiin ja käytän vertailussa Tamás Forgácsin esittämää mallia ekvivalenssin lajeista. Aineisto on kerätty unkarin- ja suomenkielisistä fraasi- ja idiomisanakirjoista sekä yleissanakirjoista. Idiomi on yksi fraseologismien alaryhmistä. Idiomi koostuu vähintään kahdesta lekseemistä, jotka voidaan kirjoittaa joko yhteen tai erikseen. Idiomi on puhtaimmillaan opaakki, kiteytynyt sanaliitto, mutta idiomi voi olla myös osittain sananmukaisesti tulkittavissa. Idiomaattisuuden ja metaforisuuden aste on jatkumo, jonka toisessa päässä ovat täysin läpinäkymättömät ja toisessa transparentit sanaliitot. Idiomit ovat puhtaimmillaan tiettyyn kieleen sidottuja. Idiomit voivat olla kuitenkin laajalevikkisiä, koska niitä on lainattu eri kieliin suoraan kääntämällä esimerkiksi Raamatusta tai antiikin teksteistä. Viime vuosisatojen ja vuosikymmenten idiomit ovat hypoteettisesti useimmiten käännöslainoja jostain Euroopan valtakielestä. Värinnimitutkimuksen tunnetuimpia teorioita on Berlinin ja Kayn teoria kielessä esiintyvien värinnimien järjestyksestä. Heidän mukaansa musta, valkoinen ja punainen esiintyvät maailman kielissä kaikista yleisimmin, sininen, ruskea ja harmaa puolestaan esiintyvät vain korkeakulttuureissa, eivät esimerkiksi luonnonkansojen kielissä. Hypoteesini on, että aineistossa esiintyvien värinnimien lukumäärä korreloi jossain määrin Berlinin ja Kayn esittämän värinnimien järjestyksen kanssa. Täysin identtisiä idiomeja sanastoltaan ja merkitykseltään löytyy aineistosta suhteellisen paljon, useimmat näistä ovat valkoisen, mustan tai harmaan värin sisältäviä idiomeja. Täysin toisiaan vastaavista idiomeista suurin osa on tullut unkariin ja suomeen Raamatusta tai lainattu sellaisenaan englannista, saksasta tai ranskasta. Osittaisessa vastaavuussuhteessa ja funktionaalisessa vastaavuussuhteessa löytyy värinnimien kannalta mielenkiintoisimmat idiomit: keltainen ja vihreä esiintyvät parissa idiomissa ristikkäin. Pääasiassa idiomeissa esiintyvät värinnimet ovat unkarin ja suomen välillä identtisiä, mikäli unkarilaiselle idiomille löytyy vastine suomen kielestä. Idiomit ilman vastinetta ovat aineiston suurin ja samalla myös kirjavin ryhmä analysoitavaksi, pienin ryhmä puolestaan ovat leksikaalisen vastaavuuden ryhmään kuuluvat idiomit. Suurin osa unkarilaisista idiomeista on työssä analysoitu, mutta suomenkieliset vastineettomat idiomit jäävät vähäiselle huomiolle tutkimusongelman näkökulmasta johtuen. Aineiston 143 unkarilaisesta idiomista noin puolet sijoittuu nollaekvivalenssin eli vastineettomien idiomien ryhmään. Täydellisen ekvivalenssin ryhmä on toiseksi suurin, leksikaalisen vastaavuuden ryhmä pienin. Idiomeissa esiintyvistä väreistä yleisimpiä ovat musta, valkoinen, punainen ja vihreä. Ruskeaa väriä ei esiinny unkarilaisissa idiomeissa lainkaan, suomalaisissa idiomeissa viidessä. Unkarin ja suomen värien merkityskentät vastaavat pitkälti toisiaan. Ainoastaan keltainen ja vihreä esiintyivät selkeästi ristikkäin: unkariksi kateus on keltaista ja suomeksi vihreää, tulokkaaseen liitetään unkarissa vihreä, suomessa keltainen väri.

Systems between information and knowledge : In a memory management model of an extended enterprise

The research question of this thesis was how knowledge can be managed with information systems. Information systems can support but not replace knowledge management. Systems can mainly store epistemic organisational knowledge included in content, and process data and information. Certain value can be achieved by adding communication technology to systems. All communication, however, can not be managed. A new layer between communication and manageable information was named as knowformation. Knowledge management literature was surveyed, together with information species from philosophy, physics, communication theory, and information system science. Positivism, post-positivism, and critical theory were studied, but knowformation in extended organisational memory seemed to be socially constructed. A memory management model of an extended enterprise (M3.exe) and knowformation concept were findings from iterative case studies, covering data, information and knowledge management systems. The cases varied from groups towards extended organisation. Systems were investigated, and administrators, users (knowledge workers) and managers interviewed. The model building required alternative sets of data, information and knowledge, instead of using the traditional pyramid. Also the explicit-tacit dichotomy was reconsidered. As human knowledge is the final aim of all data and information in the systems, the distinction between management of information vs. management of people was harmonised. Information systems were classified as the core of organisational memory. The content of the systems is in practice between communication and presentation. Firstly, the epistemic criterion of knowledge is not required neither in the knowledge management literature, nor from the content of the systems. Secondly, systems deal mostly with containers, and the knowledge management literature with applied knowledge. Also the construction of reality based on the system content and communication supports the knowformation concept. Knowformation belongs to memory management model of an extended enterprise (M3.exe) that is divided into horizontal and vertical key dimensions. Vertically, processes deal with content that can be managed, whereas communication can be supported, mainly by infrastructure. Horizontally, the right hand side of the model contains systems, and the left hand side content, which should be independent from each other. A strategy based on the model was defined.

Ortodonttien alueellinen jakautuminen Suomessa

Tutkimuksen tavoitteena oli selvittää ortodonttien tilannetta Suomessa: ikä- ja sukupuolijakaumaa, pää- ja sivutyöpaikkojen alueellista jakautumista kunta- ja sairaanhoitopiiritasolla, ortodonttien työssäkäyntialueita sekä sitä, oliko syntymä- ja koulutuspaikkakunnalla merkitystä myöhemmän työskentelypaikkakunnan valinnassa. Tutkimuksessa tarvittavat tiedot kerättiin aineiston pohjana olevaan listaan Suomen työikäisistä oikomishoidon erikoishammaslääkäreistä. Tutkimusaineistoa analysoitiin ja käsiteltiin tilastollisin keinoin. Tulokset havainnollistettiin teemakarttojen, diagrammien sekä taulukoiden avulla. Vuonna 2010 Suomessa toimi 159 ortodonttia, joista 75 prosenttia oli yli 45-vuotiaita. Eniten ortodontteja oli sijoittunut hammaslääketieteen koulutusta antavien yliopistokaupunkien, Helsingin, Turun ja Oulun, läheisyyteen. Vähiten ortodontteja työskenteli Itä- ja Pohjois-Suomen kunnissa. Jokaisessa sairaanhoitopiirissä ortodonttien määrä suhteessa väestöön oli liian pieni. 40 prosentilla ortodonteista sivutyöpaikka sijaitsi yli 50 kilometrin päässä päätyön paikkakunnasta ja 19 prosentilla yli 100 kilometrin päässä päätyön paikkakunnasta. Syntymä- ja ylioppilaaksitulon paikkakunnalla oli vaikutusta siihen, minne hakeuduttiin perustutkintoa opiskelemaan. Perustutkinnon suorittaneista keskimäärin 40 prosenttia jäi töihin samaan sairaanhoitopiiriin, jossa koulutusta antanut yliopisto sijaitsi. Yli puolet ortodonteista teki erikoistumisopinnot samassa yliopistossa kuin perusopinnot ja suurin osa jäi myös saman sairaanhoitopiirin alueelle töihin erikoistuttuaan.

Learning Challenges in Biogas Production for Sustainability : An activity theoretical study of a network from a swine industry chain

This study is about the challenges of learning in the creation and implementation of new sustainable technologies. The system of biogas production in the Programme of Sustainable Swine Production (3S Programme) conducted by the Sadia food processing company in Santa Catarina State, Brazil, is used as a case example for exploring the challenges, possibilities and obstacles of learning in the use of biogas production as a way to increase the environmental sustainability of swine production. The aim is to contribute to the discussion about the possibilities of developing systems of biogas production for sustainability (BPfS). In the study I develop hypotheses concerning the central challenges and possibilities for developing systems of BPfS in three phases. First, I construct a model of the network of activities involved in the BP for sustainability in the case study. Next, I construct a) an idealised model of the historically evolved concepts of BPfS through an analysis of the development of forms of BP and b) a hypothesis of the current central contradictions within and between the activity systems involved in BP for sustainability in the case study. This hypothesis is further developed through two actual empirical analyses: an analysis of the actors senses in taking part in the system, and an analysis of the disturbance processes in the implementation and operation of the BP system in the 3S Programme. The historical analysis shows that BP for sustainability in the 3S Programme emerged as a feasible solution for the contradiction between environmental protection and concentration, intensification and specialisation in swine production. This contradiction created a threat to the supply of swine to the food processing company. In the food production activity, the contradiction was expressed as a contradiction between the desire of the company to become a sustainable company and the situation in the outsourced farms. For the swine producers the contradiction was expressed between the contradictory rules in which the market exerted pressure which pushed for continual increases in scale, specialisation and concentration to keep the production economically viable, while the environmental rules imposed a limit to this expansion. Although the observed disturbances in the biogas system seemed to be merely technical and localised within the farms, the analysis proposed that these disturbances were formed in and between the activity systems involved in the network of BPfS during the implementation. The disturbances observed could be explained by four contradictions: a) contradictions between the new, more expanded activity of sustainable swine production and the old activity, b) a contradiction between the concept of BP for carbon credits and BP for local use in the BPfS that was implemented, c) contradictions between the new UNFCCC1 methodology for applying for carbon credits and the small size of the farms, and d) between the technologies of biogas use and burning available in the market and the small size of the farms. The main finding of this study relates to the zone of proximal development (ZPD) of the BPfS in Sadia food production chain. The model is first developed as a general model of concepts of BPfS and further developed here to the specific case of the BPfS in the 3S Programme. The model is composed of two developmental dimensions: societal and functional integration. The dimension of societal integration refers to the level of integration with other activities outside the farm. At one extreme, biogas production is self-sufficient and highly independent and the products of BP are consumed within the farm, while at the other extreme BP is highly integrated in markets and networks of collaboration, and BP products are exchanged within the markets. The dimension of functional integration refers to the level of integration between products and production processes so that economies of scope can be achieved by combining several functions using the same utility. At one extreme, BP is specialised in only one product, which allows achieving economies of scale, while at the other extreme there is an integrated production in which several biogas products are produced in order to maximise the outcomes from the BP system. The analysis suggests that BP is moving towards a societal integration, towards the market and towards a functional integration in which several biogas products are combined. The model is a hypothesis to be further tested through interventions by collectively constructing the new proposed concept of BPfS. Another important contribution of this study refers to the concept of the learning challenge. Three central learning challenges for developing a sustainable system of BP in the 3S Programme were identified: 1) the development of cheaper and more practical technologies of burning and measuring the gas, as well as the reduction of costs of the process of certification, 2) the development of new ways of using biogas within farms, and 3) the creation of new local markets and networks for selling BP products. One general learning challenge is to find more varied and synergic ways of using BP products than solely for the production of carbon credits. Both the model of the ZPD of BPfS and the identified learning challenges could be used as learning tools to facilitate the development of biogas production systems. The proposed model of the ZPD could be used to analyse different types of agricultural activities that face a similar contradiction. The findings could be used in interventions to help actors to find their own expansive actions and developmental projects for change. Rather than proposing a standardised best concept of BPfS, the idea of these learning tools is to facilitate the analysis of local situations and to help actors to make their activities more sustainable.

Metsän rakenteen muutokset ja liito-oravan esiintyminen Tampereen kaupunkialueella vuosina 1966–2004

Liito-orava (Pteromys volans) on havumetsävyöhykkeen varttuneissa sekametsissä esiintyvä pieni yöaktiivinen nisäkäs. Suomen liito-oravakannan on arvioitu taantuneen viimeisten vuosikymmenien aikana ja laji on luokiteltu Suomessa vaarantuneeksi. EU:n luontodirektiivissä liito-orava on mainittu erityistä suojelua vaativana lajina, jonka lisääntymis- tai levähdyspaikkoja ei saa hävittää. Liito-oravan suosimat varttuneet kuusivaltaiset sekametsät ovat yleisiä useiden suomalaisten kaupunkien taajama-asutusten tuntumissa. Näihin metsiin kohdistuu suuri kaavoituspaine. Tutkimuksen tarkoituksena on selvittää metsämaiseman rakenteen muutoksen vaikutusta liito-oravaan ja arvioida eroavatko kaupunki- ja metsätalousalueet liito-oravan elinympäristönä. Selvitin Tampereen kaupungin ja Kangasalan kunnan alueella sijaitsevan tutkimusalueen metsärakenteen muutokset vuosina 1966—2004 ja liito-oravaesiintymät vuonna 2004. Tarkoituksena on selvittää miten metsärakenteen muutos on vaikuttanut alueen liito-oravakantaan ja liito-oravien esiintymiseen. Ilmakuvatulkinnalla rajasin 52 km2 kokoisen tutkimusalueen metsät niiden rakenteen perusteella metsäkuvioihin. Keväällä 2004 kartoitettiin tutkimusalueen liito-oravaesiintymiä ja kirjasin metsäkuvioiden tärkeimmät puustotiedot. Luokittelin kaikki metsäkuviot neljään, liito-oravalle soveltuvuuteen perustuvaan luokkaan. Paikkatieto-ohjelmassa annoin kullekin kuvioluokalle eri värin ja lopputuloksena oli monivärinen kartta josta pystyy helposti havaitsemaan liito-oravalle soveltuvat, sopimattomat sekä liikkumiseen soveltuvat alueet. Ilmakuvatulkinnalla tein vastaavia karttoja myös vuosille 1966, 1979, 1987 ja 1995. Metsäkuviotietojen perusteella laskin eri vuosille pirstoutumista kuvaavan läheisyysindeksin. Aiemmin Etelä-Suomesta saatuja liito-orava radiopantatutkimustuloksia ja monivuotisia kartoitustuloksia vertailuaineistona käyttäen tein arvion liito-oravaesiintymien määrän kehityksestä vuosina 1966–2004. Tutkimusalueen liito-oravakartoituksessa löysin 318 papanahavaintopaikkaa. Papanahavainnoista 78 % olivat enintään 500 m päässä lähimmästä ihmisasutuksesta. Tampereen kaupungin alueen havainnoista 73 % sijaitsevat Tampereen kaupungin omistamilla alueilla. Liito-oravalle sopivien metsien pinta-ala on vuosina 1966–2004 laskenut 48,8 %. ja liito-oravalle sopimattomien alueiden pinta-ala on kasvanut 22 %. Liikkumiselle soveltuva metsäpinta-ala on kasvanut 46,3 %. Liito-oravalle sopivien laikkujen keskikoko on laskenut 13,1 hehtaarista 4,7 hehtaariin ja alue on voimakkaasti pirstoutunut. Arvion mukaan Tampereen tutkimusalueen asuttujen liito-orava elinpiirien määrä on laskenut vuosina 1966–2004 yli 59 %. Tutkimusalueen metsiköiden kehitys on ollut vastaava kuin muilla metsätalousalueilla eteläisessä Suomessa. Kaupungin läheisyys ei ole merkittävästi vaikuttanut kehitykseen. Metsänhakkuiden ja asutuksen pirstomassa maisemassa viherkäytävien merkitys korostuu. Kuitenkin suuri osa liito-oravaesiintymistä sijaitsee kaupungin mailla ja jäljellä oleva soveltuvan metsän määrä on niin pieni ja pirstoutunut, että tulevaisuuden kaavoitustoimilla ja metsänkäsittelyllä tulee olemaan suuri vaikutus paikalliseen liito-oravakantaan.

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.