Eurasian large mammal dynamics in response to changing environments during the Late Neogene

Nisäkkäiden levinneisyyteen, niiden morfologisiin ja ekologisiin piirteisiin vaikuttavat ympäristön sekä lyhyet että pitkäkestoiset muutokset, etenkin ilmaston ja kasvillisuuden vaihtelut. Työssä tutkittiin nisäkkäiden sopeutumista ilmastonmuutoksiin Euraasiassa viimeisen 24 miljoonan vuoden aikana. Tutkimuksessa keskityttiin varsinkin viimeiseen kahteen miljoonaan vuoteen, jonka aikana ilmasto muuttui voimakkaasti ja ihmisen toiminta alkoi tulla merkittäväksi. Tämän takia on usein vaikea erottaa, kummasta em. seikasta jonkin nisäkäslajin sukupuutto tai häviäminen alueelta johtui. Aineistona käytettiin laajaa venäjänkielistä kirjallisuutta, josta löytyvät tiedot ovat kääntämättöminä jääneet aiemmin länsimaisen tutkimuksen ulkopuolelle. Työssä käytettiin myös NOW-tietokantaa, jossa on fossiilisten nisäkkäiden löytöpaikat sekä niiden iät.

ORP1L, a new Rab7 effector and regulator of late endosome functions

Oxysterol binding protein (OSBP) homologues have been found in eukaryotic organisms ranging from yeast to humans. These evolutionary conserved proteins have in common the presence of an OSBP-related domain (ORD) which contains the fully conserved EQVSHHPP sequence motif. The ORD forms a barrel structure that binds sterols in its interior. Other domains and sequence elements found in OSBP-homologues include pleckstrin homology domains, ankyrin repeats and two phenylalanines in an acidic tract (FFAT) motifs, which target the proteins to distinct subcellular compartments. OSBP homologues have been implicated in a wide range of intracellular processes, including vesicle trafficking, lipid metabolism and cell signaling, but little is known about the functional mechanisms of these proteins. The human family of OSBP homologues consists of twelve OSBP-related proteins (ORP). This thesis work is focused on one of the family members, ORP1, of which two variants were found to be expressed tissue-specifically in humans. The shorter variant, ORP1S contains an ORD only. The N-terminally extended variant, ORP1L, comprises a pleckstrin homology domain and three ankyrin repeats in addition to the ORD. The two ORP1 variants differ in intracellular localization. ORP1S is cytosolic, while the ankyrin repeat region of ORP1L targets the protein to late endosomes/lysosomes. This part of ORP1L also has profound effects on late endosomal morphology, inducing perinuclear clustering of late endosomes. A central aim of this study was to identify molecular interactions of ORP1L on late endosomes. The morphological changes of late endosomes induced by overexpressed ORP1L implies involvement of small Rab GTPases, regulators of organelle motility, tethering, docking and/or fusion, in generation of the phenotype. A direct interaction was demonstrated between ORP1L and active Rab7. ORP1L prolongs the active state of Rab7 by stabilizing its GTP-bound form. The clustering of late endosomes/lysosomes was also shown to be linked to the minus end-directed microtubule-based dynein-dynactin motor complex through the ankyrin repeat region of ORP1L. ORP1L, Rab7 and the Rab7-interacting lysosomal protein (RILP) were found to be part of the same effector complex recruiting the dynein-dynactin complex to late endosomes, thereby promoting minus end-directed movement. The proteins were found to be physically close to each other on late endosomes and RILP was found to stabilize the ORP1L-Rab7 interaction. It is possible that ORP1L and RILP bind to each other through their C-terminal and N-terminal regions, respectively, when they are bridged by Rab7. With the results of this study we have been able to place a member of the uncharacterized OSBP-family, ORP1L, in the endocytic pathway, where it regulates motility and possibly fusion of late endosomes through interaction with the small GTPase Rab7.

DNA Packaging and Host Cell Lysis: Late Events in Bacteriophage PRD1 Infection

The object of this study is a tailless internal membrane-containing bacteriophage PRD1. It has a dsDNA genome with covalently bound terminal proteins required for replication. The uniqueness of the structure makes this phage a desirable object of research. PRD1 has been studied for some 30 years during which time a lot of information has accumulated on its structure and life-cycle. The two least characterised steps of the PRD1 life-cycle, the genome packaging and virus release are investigated here. PRD1 shares the main principles of virion assembly (DNA packaging in particular) and host cell lysis with other dsDNA bacteriophages. However, this phage has some fascinating individual peculiarities, such as DNA packaging into a membrane vesicle inside the capsid, absence of apparent portal protein, holin inhibitor and procapsid expansion. In the course of this study we have identified the components of the DNA packaging vertex of the capsid, and determined the function of protein P6 in packaging. We managed to purify the procapsids for an in vitro packaging system, optimise the reaction and significantly increase its efficiency. We developed a new method to determine DNA translocation and were able to quantify the efficiency and the rate of packaging. A model for PRD1 DNA packaging was also proposed. Another part of this study covers the lysis of the host cell. As other dsDNA bacteriophages PRD1 has been proposed to utilise a two-component lysis system. The existence of this lysis system in PRD1 has been proven by experiments using recombinant proteins and the multi-step nature of the lysis process has been established.

Mitochondrial helicase Twinkle in mtDNA copy number regulation and a late-onset disease model

Mitochondrial diseases are caused by disturbances of the energy metabolism. The disorders range from severe childhood neurological diseases to muscle diseases of adults. Recently, mitochondrial dysfunction has also been found in Parkinson s disease, diabetes, certain types of cancer and premature aging. Mitochondria are the power plants of the cell but they also participate in the regulation of cell growth, signaling and cell death. Mitochondria have their own genetic material, mtDNA, which contains the genetic instructions for cellular respiration. Single cell may host thousands of mitochondria and several mtDNA molecules may reside inside single mitochondrion. All proteins needed for mtDNA maintenance are, however, encoded by the nuclear genome, and therefore, mutations of the corresponding genes can also cause mitochondrial disease. We have here studied the function of mitochondrial helicase Twinkle. Our research group has previously identified nuclear Twinkle gene mutations underlying an inherited adult-onset disorder, progressive external ophthalmoplegia (PEO). Characteristic for the PEO disease is the accumulation of multiple mtDNA deletions in tissues such as the muscle and brain. In this study, we have shown that Twinkle helicase is essential for mtDNA maintenance and that it is capable of regulating mtDNA copy number. Our results support the role of Twinkle as the mtDNA replication helicase. No cure is available for mitochondrial disease. Good disease models are needed for studies of the cause of disease and its progression and for treatment trials. Such disease model, which replicates the key features of the PEO disease, has been generated in this study. The model allows for careful inspection of how Twinkle mutations lead to mtDNA deletions and further causes the PEO disease. This model will be utilized in a range of studies addressing the delay of the disease onset and progression and in subsequent treatment trials. In conclusion, in this thesis fundamental knowledge of the function of the mitochondrial helicase Twinkle was gained. In addition, the first model for adult-onset mitochondrial disease was generated.

Late results after paediatric cardiac surgery

Background: Congenital heart defects include a wide range of inborn malformations. Depending on the defect, the life expectancy of a newborn with cardiac anomaly varies from a few days to a normal life span. In most instances surgery, is the only treatment available. The late results of surgery have not been comprehensively investigated. Aims: Mortality, morbidity and the life situation of all Finnish patients who had been operated on for congenital heart defect during childhood were investigated. Methods: Patient and surgical data were gathered from all hospitals that had performed heart surgeries on children. Late mortality and survival data were obtained from the population registry, and the causes of deaths from Statistics Finland. Morbidity of patients operated on during 1953-1989 was assessed by the usage of medicines. The pharmacotherapy data of patients and controls were obtained from the Social Insurance Institute. The life situation of patients was surveyed by mailed questionnaire. Survival, causes of deaths and life situation of patients were compared with those of the general population. Results: A total of 7240 cardiac operations were performed on 6461 children during the first 37 years of cardiac surgery (1953-1989). The number of procedures constantly rose during this period, and the increase continued in later years. The patient material varied over time, as more defects became surgically treatable. During 1953-1989 the operative mortality (death within 30 days of surgery) was 6.9%. In the 1990s a slight rise occurred in early mortality, as increasingly complicated patients were surgically treated. During 2000-2003 practically no defects were beyond the operative range. Thus, the operative mortality of 4.4% was excellent, decreasing even further to 2.0% in 2004-2007. The overall 45-year survival of patients operated on in 1953-1989 was 78%, and the corresponding figure for the general population was 93%. Survival depended on the defect, being worst among patients with univentricular heart. Late survival was also better during the 1990s and at the beginning of the 21st century. Of the 6028 early survivors, 592 died late (>30 days) after surgery. A total of 397 deaths (67%) were related and 185 (31%) unrelated to congenital heart defect. The cause of death was unknown in 10 cases. Of those 5774 patients who survived their first operation and had complete follow-up, 16% were operated on several times. Seventeen percent of patients used medicines for cardiac symptoms (heart failure, arrhythmia, hypertension and coronary disease). Patients risk of using cardiac medicines was 2.16 (Cl 1.97-2.37) times higher than that of controls. Patients also had more genetic syndromes and mental retardation and more often used medicines for asthma and epilepsy. Adult patients who had been operated on as children had coped surprisingly well with their defects. Their level of education was similar and their employment level even higher than expected, and they were living in a steady relationship as often as the general population. Conclusions: Cardiac surgery developed rapidly, and nowadays practically all defects can be treated. The overall survival of all operated patients was 78%, 16% less than that of the general population. However, it was significantly better than the anticipated natural survival. However, many patients had health problems; 16% needed reoperations and 17% cardiac medicines to maintain their condition. Most of the patients assessed their general health as good and lived a normal life.

Sterol-binding proteins in late endosomes : Regulation of endosome motility and lipid metabolism

Despite its bad reputation in the mass media, cholesterol is an indispensable constituent of cellular membranes and vertebrate life. It is, however, also potentially lethal as it may accumulate in the arterial intima causing atherosclerosis or elsewhere in the body due to inherited conditions. Studying cholesterol in cells, and research on how the cell biology of cholesterol affects on system level is essential for a better understanding of the disease states associated with cholesterol and for the development of new therapies for these conditions. On its way to the cell, exogenous cholesterol traverses through endosomes, transport vesicles involved in internalizing material to cells, and needs to be transported out of this compartment. This endosomal pool of cholesterol is important for understanding both the common disorders of metabolism and the more rare hereditary disorders of cholesterol metabolism. The study of cholesterol in cells has been hampered by the lack of bright fluorescent sterol analogs that would resemble cholesterol enough to be used in cellular studies. In the first study of my thesis, we present a new sterol analog, Boron-Dipyrromethene (BODIPY)-cholesterol for visualizing sterols in living cells and organism. This fluorescent cholesterol derivative is shown to behave similarly to cholesterol both by atomic scale computer simulations and biochemical experiments. We characterize its localization inside different types of living cells and show that it can be used to study sterol trafficking in living organisms. Two sterol binding proteins associated with the endosomal membrane; the Niemann-Pick type C disease protein 1 (NPC1) and the Oxysterol Binding Protein Related Protein 1 (ORP1) are the subjects of the rest of this study. Sensing cholesterol on endosomes, transporting lipids away from this compartment and the effects these lipids play on cellular metabolism are considered. In the second study we characterize how the NPC1 protein affects lipid metabolism. We show that this cholesterol binding protein affects synthesis of triglycerides and that genetic polymorphisms or a genetic defect in the NPC1 gene affect triglyceride on the whole body level. These effects take place via regulation of carbon fluxes to different lipid classes in cells. In the third part we characterize the effects of another endosomal sterol binding protein, ORP1L on the function and motility of endosomes. Specifically we elucidate how a mutation in the ability of ORP1L to bind sterols affects its behavior in cells, and how a change in ORP1L levels in cells affects the localization, degradative capacity and motility of endosomes. In addition we show that ORP1L manipulations affect cholesterol balance also in macrophages, a cell type important for the development of atherosclerosis.

Late Svecofennian leucogranites of southern Finland : Chronicles of an orogenic collapse

Leucogranite magmatism occurred in southern Finland during the later stages of the Paleoproterozoic Svecofennian orogeny. The leucogranites are considered to have formed from pre-existing crustal rocks that have undergone anatexis in the extensional stage of the orogeny, following continental collision and resultant crustal thickening. The leucogranites have been studied in the field using petrographic and mineralogical methods, elemental and isotope geochemistry on whole rocks and minerals, and U-Pb geochronology. On outcrop scale, these granites typically form heterogeneous, layered, sheet-like bodies that migmatize their country rocks. All of the leucogranites are peraluminous and rich in SiO2, but otherwise display significant geochemical variation. Their Nd isotope composition ranges from fairly juvenile to very unradiogenic, and the Hf isotope composition of their zircon shows a varying degree of mixing in the source, the zircon populations becoming more heterogeneous and generally less radiogenic towards the east. The leucogranites have been dated using U-Pb isotopic analyses, utilizing thermal ionization mass spectrometry, secondary ion mass spectrometry, and laser ablation multicollector ICP mass spectrometry on zircon and monazite. The results show that the granites were emplaced between 1.85 Ga and 1.79 Ga, which is a considerably longer period than has traditionally been perceived for these rocks. The rocks tend to become younger towards the east. Single crystal data also display a wide array of inherited zircons, especially in the eastern part of the leucogranite belt. The most common inherited age groups are ~2.8 2.5 Ga, ~2.1 2.1 Ga, and ~1.9 Ga. Magmatic zircon and monazite usually record similar ages for any one sample.Thermobarometric calculations indicate that the leucogranites in the Veikkola area of southcentral Finland were formed from relatively low-temperature melts, and emplaced at 17-25 km depth, i.e. at mid-crustal level. It is likely that these conditions apply to the Svecofennian leucogranites in general. Large differences in the Hf and Nd isotope compositions, emplacement ages, and distributions of inherited zircon ages show that these granites were formed from different types of source rocks, which probably included both sedimentary and igneous rocks.

“Empire is a state of mind” – Imagining Eurasia in Russia –

Työssäni tarkastelen venäläistä neo-euraasianistista liikettä ja tapoja joilla liikkeen aktivistit rakentavat Euraasiasta yhtenäistä kokonaisuutta ja imperiumia. Keskeisiä tutkimuskysymyksiäni ovat: Mikä imperiumi on ja mitkä ovat sen keskeisiä motivaatioita ja teemoja? Kuinka imperiumin idea rakentuu tai käsitetään ja tämän voi tulkita? Minkälaisia seurauksia voi tulkita heidän tavallaan Euraasia nähdä olevan? Materiaalina käytän haastatteluja, jotka on kerätty Moskovassa keväällä 2008, ja liikkeen kirjallisia tuotoksia (lehdet ja Internet -sivut). Neo-euraasianistisella liikkeellä tarkoitan tässä työssä Kansainvälistä Euraasianistista liikettä (Meždunarodnoe Evrazijskoe Dviženie) ja sen alahaaraa Euraasianistista Nuorisoliittoa (Evrazijskij Sojuz Molodëži). Liike perustettiin virallisesti 2003, mutta rakentaa vahvasti historiallista yhteyttä 1930 -luvun klassiseen eurasianismiin. Tämän lisäksi sen diskurssissa on paljon neuvostoliittolaisia, fasistisia, uuskonservatiivisia ja nationalistisia piirteitä. Liikkeen johtohahmo on filosofi-geopoliitikko Alexandr Dugin. Työn tausta-ajatuksena minua kiinnostaa etenkin nk. älymystön tai intelligenttien vaikutus nationalismiin tai sosiaalisia ryhmiä määrittelevien diskurssien kehitykseen ja muutokseen.Tarkastelen materiaalia diskurssianalyyttisesta näkökulmasta. Näen diskurssianalyysin sen tutkimisena, miten sosiaalista todellisuutta tuotetaan erilaisissa sosiaalisissa käytännöissä. Samalla näiden diskurssien tutkiminen, foucautlaisen perinteen myötä, tarkastelee kriittisesti niiden tuottamia (aktualisoituneita sekä potentiaalisia) valtasuhteita. Käytän työssäni myös Benedict Andersonin kuvitellun yhteisön (imagined communities) käsitettä, joka auttaa hahmottamaan tapaa, jolla tutkimuskohteeni rakentavat imperiumia yhteisönä. Aktivistien puheessa imperiumi (imperiâ) tulee esiin pääasiallisesti positiivisesti ja ”heidän omanaan,” kun taas termi imperialismi (imperializm) pääosin negatiivisena, liittyen etenkin keskeisenä vihollisena pidettyihin Yhdysvaltoihin. Esiin nousee monta toisiinsa liittyvää teemaa, jotka jaottelen viideksi pääteemaksi. Näistä tarkastelen lähemmin imperiumia ”kaikkien kansojen hyväntekijänä (poliittinen puoli)”, ulkoisen voiman lähteenä (historiallis-geopoliittinen puoli) sekä kollektiivisen subjektin luojana (imperialistis-nationalistinen puoli). Pyrin kontekstualisoimaan diskurssin ja tarkastelemaan tapoja, joilla se ammentaa motiiveja myös historiallis-kulttuurisista tavoista hahmottaa aluetta ja sen asukkaita. Käsittelen myös kansan, kansakunnan, etnoksen ja nationalismin käsitteitä ja sitä, miten ne nousevat neo-eurasianistisessa diskursissa esiin. Imperiaalisen nationalismin (imperskij nacionalizm) käsite auttaa ymmärtämään niitä tapoja, jolla liike tekee sekä pesäeroa nationalismiin että samalla hyödyntää monia nationalistisen diskurssin perusteemoja. Eräs liikkeen diskurssin keskeisistä eroista niin sanottuun nationalismin valtavirtaan on ”kansakunnan (naciâ)” käsitteen vahva negatiivinen konnotaatio. Sen vastakohtana esiin nostetaan vahvasti kansan (narod) käsite. Samalla kuitenkin etnisen venäläisen (russkij) käsitettä käytetään tavallista laajemmin ja kattavammin kuin tavallisesti, ja ennen kaikkea Venäjä nousee imperiumin keskeisimmäksi tekijäksi. Euraasialaiseen imperiumiin liitetyistä positiivistista mielikuvista käsittelen tarkemmin monikansallisuuden ja kansojen kodin ideaa, joka nousee mielestäni huomattavaksi retoriseksi taustaksi kaikessa materiaalissa. Tähän liittyy vahvasti myös saman teeman sivujuonne, eli imperiumin ”vapauttava” rooli. Tulkitsen, että liikkeen imperiumi -diskurssilla on instrumentaalinen luonne: se legitimoi aktivistien vaatimuksia varsinkin entisen Neuvostoliiton alueen suhteen. ”Euraasialaisen kansan” ajatus toimii mahdollisena Euraasiaa yhteisenä tekijänä ”Neuvostokansan” tilalla. Sen taustalla materiaalistani päätellen siintävät kuitenkin enemmänkin Venäjä ja venäläis -spesifit vaateet kuin koko Euraasia. Pohdin myös kansakunnan (nation) hyljeksimisen syitä ja käsitteen sopivuutta Venäjälle, kuten myös venäläisyyden käsitteiden kerrostuneisuutta. Kokonaisuudessaan imperiumi tuli esiin abstraktina, utopistisena ja ”totaalisena” kokonaisuutena.

Evil Gods and Reckless Saviours : Adaptation and Appropriation in Late Twentieth Century Jesus-Novels

Late twentieth century Jesus-novels search after a completely new picture of Jesus. Novels written for instance by Norman Mailer, José Saramago, Michèle Roberts, Marianne Fredriksson, and Ki Longfellow provide an inversive revision of the canonic Gospels. They read the New Testament in terms of the present age. In their adaptation the story turns often into a critique of the whole Christian history. The investigated contrast-novels end up with an appropriation that is based on prototypical rewriting. They aim at the rehabilitation of Judas, and some of them make Mary Magdalane the key figure of Christianity. Saramago describes God as a blood thirsty tyrant, and Mailer makes God combat with the Devil in a manichean sense as with an equal. Such ideas are familiar both from poststructuralist philosophy and post-metaphysical death-of-God theology. The main result of the intertextual analysis is that these scholars have adopted Nietzschean ideas in their writing. Quite unlike earlier Jesus-novels, these more recent novels present a revision that produces discontinuity with the original source text, the New Testament. The intertextual strategy is based on contradiction. The reader wittnesses contesting and challenging, the authors attack Biblical beliefs and attempt to dissolve Christian doctrines. An attack on Biblical slave morality and violent concept of God deprives Jesus of his Jewish Messianic identity, makes Old Testament law a contradiction of life, calls sacrificial soteriology a violent pattern supporting oppression, and presents God as a cruel monster who enslaves people under his commandments and wishes their death. The new Jesus-figure contests Mosaic Law, despises orthodox Judaism, abandons Jewish customs and even questions Old Testament monotheism. In result, the novels intentionally transfer Jesus out of Judaism. Furthermore, Jewish faith appears in a negative light. Such an intertextual move is not open anti-Semitism but it cannot avoid attacking Jewish worship. Why? One reason that explains these attitudes is that Western culture still carries anti-Judaic attitudes beneath the surface covered with sentiments of equality and tolerance. Despite the evident post-holocaust consciousness present in the novels, they actually adopt an arrogant and ironical refutation of Jewish beliefs and Old Testament faith. In these novels, Jesus is made a complete opposite and antithesis to Judaism. Key words: Jesus-novel, intertextuality, adaptation, slave morality, Nietzsche, theodicy, patriarchy.

Late-industrial sawmill customers.

The methods of secondary wood processing are assumed to evolve over time and to affect the requirements set for the wood material and its suppliers. The study aimed at analysing the industrial operating modes applied by joinery and furniture manufacturers as sawnwood users. Industrial operating mode was defined as a pattern of important decisions and actions taken by a company which describes the company's level of adjustment in the late-industrial transition. A non-probabilistic sample of 127 companies was interviewed, including companies from Denmark, Germany, the Netherlands, and Finland. Fifty-two of the firms were furniture manufacturers and the other 75 were producing windows and doors. Variables related to business philosophy, production operations, and supplier choice criteria were measured and used as a basis for a customer typology; variables related to wood usage and perceived sawmill performance were measured to be used to profile the customer types. Factor analysis was used to determine the latent dimensions of industrial operating mode. Canonical correlations analysis was applied in developing the final base for classifying the observations. Non-hierarchical cluster analysis was employed to build a five-group typology of secondary wood processing firms; these ranged from traditional mass producers to late-industrial flexible manufacturers. There is a clear connection between the amount of late-industrial elements in a company and the share of special and customised sawnwood it uses. Those joinery or furniture manufacturers that are more late-industrial also are likely to use more component-type wood material and to appreciate customer-oriented technical precision. The results show that the change is towards the use of late-industrial sawnwood materials and late-industrial supplier relationships.