Paleomagnetic and rock magnetic study with emphasis on the Precambrian intrusions and impact structures in Fennoscandia and South Africa

The importance of supercontinents in our understanding of the geological evolution of the planet Earth has been recently emphasized. The role of paleomagnetism in reconstructing lithospheric blocks in their ancient paleopositions is vital. Paleomagnetism is the only quantitative tool for providing ancient latitudes and azimuthal orientations of continents. It also yields information of content of the geomagnetic field in the past. In order to obtain a continuous record on the positions of continents, dated intrusive rocks are required in temporal progression. This is not always possible due to pulse-like occurrences of dykes. In this work we demonstrate that studies of meteorite impact-related rocks may fill some gaps in the paleomagnetic record. This dissertation is based on paleomagnetic and rock magnetic data obtained from samples of the Jänisjärvi impact structure (Russian Karelia, most recent 40Ar-39Ar age of 682 Ma), the Salla diabase dyke (North Finland, U-Pb 1122 Ma), the Valaam monzodioritic sill (Russian Karelia, U-Pb 1458 Ma), and the Vredefort impact structure (South Africa, 2023 Ma). The paleomagnetic study of Jänisjärvi samples was made in order to obtain a pole for Baltica, which lacks paleomagnetic data from 750 to ca. 600 Ma. The position of Baltica at ca. 700 Ma is relevant in order to verify whether the supercontinent Rodinia was already fragmented. The paleomagnetic study of the Salla dyke was conducted to examine the position of Baltica at the onset of supercontinent Rodinia's formation. The virtual geomagnetic pole (VGP) from Salla dyke provides hints that the Mesoproterozoic Baltica - Laurentia unity in the Hudsonland (Columbia, Nuna) supercontinent assembly may have lasted until 1.12 Ga. Moreover, the new VGP of Salla dyke provides new constraint on the timing of the rotation of Baltica relative to Laurentia (e.g. Gower et al., 1990). A paleomagnetic study of the Valaam sill was carried out in order to shed light into the question of existence of Baltica-Laurentia unity in the supercontinent Hudsonland. Combined with results from dyke complex of the Lake Ladoga region (Schehrbakova et al., 2008) a new robust paleomagnetic pole for Baltica is obtained. This pole places Baltica on a latitude of 10°. This low latitude location is supported also by Mesoproterozoic 1.5 1.3 Ga red-bed sedimentation (for example the Satakunta sandstone). The Vredefort impactite samples provide a well dated (2.02 Ga) pole for the Kaapvaal Craton. Rock magnetic data reveal unusually high Koenigsberger ratios (Q values) in all studied lithologies of the Vredefort dome. The high Q values are now first time also seen in samples from the Johannesburg Dome (ca. 120 km away) where there is no impact evidence. Thus, a direct causative link of high Q values to the Vredefort impact event can be ruled out.

Direct and Inverse Scattering for Beltrami Fields

We consider an obstacle scattering problem for linear Beltrami fields. A vector field is a linear Beltrami field if the curl of the field is a constant times itself. We study the obstacles that are of Neumann type, that is, the normal component of the total field vanishes on the boundary of the obstacle. We prove the unique solvability for the corresponding exterior boundary value problem, in other words, the direct obstacle scattering model. For the inverse obstacle scattering problem, we deduce the formulas that are needed to apply the singular sources method. The numerical examples are computed for the direct scattering problem and for the inverse scattering problem.

The community of medium-sized carnivores: the interactions between species, habitats and rabies

The composition of the carnivore community influences the different forms of inter-specific interactions. Furthermore, inter-specific interactions of carnivores have important implications for intra-guild competition, epidemiology and strategies of species-specific population management. Zoonooses, such as rabies, are diseases that can be transmitted from wildlife to people. Knowing the ecological characteristics of the species helps us to choose the right preventive actions and to time them accurately. In this thesis, I have studied how raccoon dogs Nyctereutes procyonoides, European badgers Meles meles, red foxes Vulpes vulpes and domestic cats Felis silvestris catus act as members of carnivore community, and how these interactions relate to the transmission risk of rabies. In the study area, these species form a community of medium-sized and rather generalist predators. They live in the same areas, in spatially and temporally overlapping home ranges and use the same habitats and dens and even have similar diets. However, there is no direct evidence of competition. Shared dens point to good tolerance of other species. Numerous observations of animals moving in each other’s proximity give similar clues. However, overlapping home ranges and similar habitat preferences lead to frequent inter-specific contacts, which increase the risk of possible rabies transmission. Also, the new insight of habitat use gained by this study illustrates the similar favouring of deciduous forests and fields by these sympatric medium-sized carnivores, creating a basis for contact zones, i.e. risky habitats for rabies transmission and spread. This study is so far the only simultaneous radio tracking study of raccoon dogs, badgers, foxes and cats. These results give new insight of the interactions in the carnivore community, as well as of the behaviour of each individual species. Also, these results have significant implications for the planning of rabies control. In order to reach viable management decisions, not only one or two species should be taken into consideration, but the whole community. In particular, this changes the perspective to inter-specific contacts, animal densities, densities of individuals susceptible to diseases and the magnitude of preventive actions. Rabies should be considered as a multi-vector disease, at least in Finland and the Baltic states. It is of interest for disease management to be able to model an epizootic with local parameters to reflect the real situation and also to suite best the local management needs.

Role of HMGB1 in cells of the circulation

The matrix of blood is a liquid plasma that transports molecules and blood cells within vessels lined by endothelial cells. High-mobility group B1 (HMGB1) is a protein expressed in blood cells. Under normal circumstances, HMGB1 is virtually absent from plasma, but during inflammation or trauma its level in plasma is increased. In resting and quiescent cells, HMGB1 is usually localized in the intracellular compartment, with the exception of motile cells that express HMGB1 on their outer surface to mediate cell migration. During cell transformation or immune cell activation HMGB1 can be actively secreted outside of the cell. Further, when a cell is damaged, HMGB1 can passively leak into extracellular environment. Extracellular HMGB1 can then participate in regulation of the immune response and under some conditions it can mediate lethality in systemic inflammatory response. The aim of this study was to evaluate the expression and functions of HMGB1 in cells of the vascular system and to investigate the prognostic value of circulating HMGB1 in severe sepsis and septic shock. HMGB1 was detected in platelets, leukocytes, and endothelial cells. HMGB1 was released from platelets and leukocytes, and it was found to mediate their adhesive and migratory functions. During severe infections the plasma levels of HMGB1 were elevated; however, no direct correlation with lethality was found. Further, the analysis of proinflammatory mechanisms suggested that HMGB1 forms complexes with other molecules to activate the immune system. In conclusion, HMGB1 is expressed in the cells of the vascular system, and it participates in inflammatory mechanisms by activating platelets and leukocytes and by mediating monocyte migration.

The life cycle and genetic structure of the red alga Furcellaria lumbricalis on a salinity gradient

The life cycle and genetic diversity of the red alga Furcellaria lumbricalis (Hudson) Lamouroux were investigated in 15 populations in northern Europe. The occurrence of different life cycle phases and seasonality of reproduction were studied in four brackish populations in the northern Baltic Sea. Furthermore, a new method, based on genome screening with ISSR markers combined with a restriction-ligation method, was developed to discover microsatellite markers for population genetic analyses. The mitochondrial DNA cox2-3 spacer sequence and four microsatellite markers were used to examine the genetic diversity and differentiation of red algal populations in northern Europe. In addition, clonality and small-scale genetic structure of one Irish and four Baltic Sea populations were studied with microsatellite markers. It was discovered that at the low salinities of the northern Baltic Sea, only tetrasporophytes and males were present in the populations of F. lumbricalis and that winter was the main season for tetrasporangial production. Furthermore, the population occurring at the lowest salinity (3.6 practical salinity units, psu) did not produce spores. The size of the tetraspores was smaller in the Baltic Sea populations than that in the Irish population, and there were more deformed spores in the Baltic Sea populations than in the Irish populations. Studies with microsatellite markers indicated that clonality is a common phenomenon in the Baltic Sea populations of F. lumbricalis, although the proportion of clonal individuals varied among populations. Some genetic divergence occurred within locations both in Ireland and in the northern Baltic Sea. Even though no carpogonia were detected in the field samples during the study, the microsatellite data indicated that sexual reproduction occurs at least occasionally in the northern Baltic Sea. The genetic diversity of F. lumbricalis was highest in Brittany, France. Since no variation was discovered in the mtDNA cox2-3 spacer sequence, which is generally regarded as an informative phylogeographic marker in red algae, it can be assumed that the studied populations probably share the same origin.

Ecological communities in variable environments : dynamics and diversity under coloured environmental stochasticity

While environmental variation is an ubiquitous phenomenon in the natural world which has for long been appreciated by the scientific community recent changes in global climatic conditions have begun to raise consciousness about the economical, political and sociological ramifications of global climate change. Climate warming has already resulted in documented changes in ecosystem functioning, with direct repercussions on ecosystem services. While predicting the influence of ecosystem changes on vital ecosystem services can be extremely difficult, knowledge of the organisation of ecological interactions within natural communities can help us better understand climate driven changes in ecosystems. The role of environmental variation as an agent mediating population extinctions is likely to become increasingly important in the future. In previous studies population extinction risk in stochastic environmental conditions has been tied to an interaction between population density dependence and the temporal autocorrelation of environmental fluctuations. When populations interact with each other, forming ecological communities, the response of such species assemblages to environmental stochasticity can depend, e.g., on trophic structure in the food web and the similarity in species-specific responses to environmental conditions. The results presented in this thesis indicate that variation in the correlation structure between species-specific environmental responses (environmental correlation) can have important qualitative and quantitative effects on community persistence and biomass stability in autocorrelated (coloured) environments. In addition, reddened environmental stochasticity and ecological drift processes (such as demographic stochasticity and dispersal limitation) have important implications for patterns in species relative abundances and community dynamics over time and space. Our understanding of patterns in biodiversity at local and global scale can be enhanced by considering the relevance of different drift processes for community organisation and dynamics. Although the results laid out in this thesis are based on mathematical simulation models, they can be valuable in planning effective empirical studies as well as in interpreting existing empirical results. Most of the metrics considered here are directly applicable to empirical data.

Laboratory analyses for evaluation of platelet disorders and platelet concentrates

High quality of platelet analytics requires specialized knowledge and skills. It was applied to analyze platelet activation and aggregation responses in a prospective controlled study of patients with Finnish type of amyloidosis. The 20 patients with AGel amyloidosis displayed a delayed and more profound platelet shape change than healthy siblings and healthy volunteers, which may be related to altered fragmentation of mutated gelsolin during platelet activation. Alterations in platelet shape change have not been reported in association with platelet disorders. In the rare Bernard-Soulier syndrome with Asn45Ser mutation of glycoprotein (GP) IX, the diagnostic defect in the expression of GPIb-IX-V complex was characterized in seven Finnish patients, also an internationally exceptionally large patient series. When measuring thrombopoietin in serial samples of amniotic fluid and cord blood of 15 pregnant women with confirmed or suspected fetal alloimmune thrombocytopenia, the lower limit of detection could be extended. The results approved that thrombopoietin is present already in amniotic fluid. The application of various non-invasive means for diagnosing thrombocytopenia (TP) revealed that techniques for estimating the proportion of young, i.e. large platelets, such as direct measurement of reticulated platelets and the mean platelet size, would be useful for evaluating platelet kinetics in a given patient. Due to different kinetics between thrombopoietin and increase of young platelets in circulation, these measurements may have most predictive value when measured from simultaneous samples. Platelet autoantibodies were present not only in isolated autoimmune TP but also in patients without TP where disappearance of platelets might be compensated by increased production. The autoantibodies may also persist after TP has been cured. Simultaneous demonstration of increased young platelets (or increased mean platelet volume) in peripheral blood and the presence of platelet associated IgG specificities to major glycoproteins (GPIb-IX and GPIIb-IIIa) may be considered diagnostic for autoimmune TP. Measurement of a soluble marker as a sign of thrombin activation and proceeding deterioration of platelet components was applied to analyze the alterations under several stress factors (storage, transportation and lack of continuous shaking under controlled conditions) of platelet products. The GPV measured as a soluble factor in platelet storage medium showed good correlation with an array of other measurements commonly applied in characterization of stored platelets. The benefits of measuring soluble analyte in a quantitative assay were evident.

Molecular mediators linking stroke and carotid artery disease

Carotid artery disease is the most prevalent etiologic precursor of ischemic stroke, which is a major health hazard and the second most common cause of death in the world. If a patient presents with a symptomatic high-grade (>70%) stenosis in the internal carotid artery, the treatment of choice is carotid endarterectomy. However, the natural course of radiologically equivalent carotid lesions may be clinically quite diverse, and the reason for that is unknown. It would be of utmost importance to develop molecular markers that predict the symptomatic phenotype of an atherosclerotic carotid plaque (CP) and help to differentiate vulnerable lesions from stable ones. The aim of this study was to investigate the morphologic and molecular factors that associate with stroke-prone CPs. In addition to immunohistochemistry, DNA microarrays were utilized to identify molecular markers that would differentiate between symptomatic and asymptomatic CPs. Endothelial adhesion molecule expression (ICAM-1, VCAM-1, P-selectin, and E-selectin) did not differ between symptomatic and asymptomatic patients. Denudation of endothelial cells was associated with symptom-generating carotid lesions, but in studies on the mechanism of decay of endothelial cells, markers of apoptosis (TUNEL, activated caspase 3) were found to be decreased in the endothelium of symptomatic lesions. Furthermore, markers of endothelial apoptosis were directly associated with those of cell proliferation (Ki-67) in all plaques. FasL expression was significantly increased on the endothelium of symptomatic CPs. DNA microarray analysis revealed prominent induction of specific genes in symptomatic CPs, including those subserving iron and heme metabolism, namely HO-1, and hemoglobin scavenger receptor CD163. HO-1 and CD163 proteins were also increased in symptomatic CPs and associated with intraplaque iron deposits, which, however, did not correlate with symptom status itself. ADRP, the gene for adipophilin, was also overexpressed in symptomatic CPs. Adipophilin expression was markedly increased in ulcerated CPs and colocalized with extravasated red blood cells and cholesterol crystals. Taken together, the phenotypic characteristics and the numerous possible molecular mediators of the destabilization of carotid plaques provide potential platforms for future research. The denudation of the endothelial lining observed in symptomatic CPs may lead to direct thromboembolism and maintain harmful oxidative and inflammatory processes, predispose to plaque microhemorrhages, and contribute to lipid accumulation into the plaque, thereby making it vulnerable to rupture.

Hematopoietic Stem Cell Development and Transcriptional Regulation

The continuous production of blood cells, a process termed hematopoiesis, is sustained throughout the lifetime of an individual by a relatively small population of cells known as hematopoietic stem cells (HSCs). HSCs are unique cells characterized by their ability to self-renew and give rise to all types of mature blood cells. Given their high proliferative potential, HSCs need to be tightly regulated on the cellular and molecular levels or could otherwise turn malignant. On the other hand, the tight regulatory control of HSC function also translates into difficulties in culturing and expanding HSCs in vitro. In fact, it is currently not possible to maintain or expand HSCs ex vivo without rapid loss of self-renewal. Increased knowledge of the unique features of important HSC niches and of key transcriptional regulatory programs that govern HSC behavior is thus needed. Additional insight in the mechanisms of stem cell formation could enable us to recapitulate the processes of HSC formation and self-renewal/expansion ex vivo with the ultimate goal of creating an unlimited supply of HSCs from e.g. human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPS) to be used in therapy. We thus asked: How are hematopoietic stem cells formed and in what cellular niches does this happen (Papers I, II)? What are the molecular mechanisms that govern hematopoietic stem cell development and differentiation (Papers III, IV)? Importantly, we could show that placenta is a major fetal hematopoietic niche that harbors a large number of HSCs during midgestation (Paper I)(Gekas et al., 2005). In order to address whether the HSCs found in placenta were formed there we utilized the Runx1-LacZ knock-in and Ncx1 knockout mouse models (Paper II). Importantly, we could show that HSCs emerge de novo in the placental vasculature in the absence of circulation (Rhodes et al., 2008). Furthermore, we could identify defined microenvironmental niches within the placenta with distinct roles in hematopoiesis: the large vessels of the chorioallantoic mesenchyme serve as sites of HSC generation whereas the placental labyrinth is a niche supporting HSC expansion (Rhodes et al., 2008). Overall, these studies illustrate the importance of distinct milieus in the emergence and subsequent maturation of HSCs. To ensure proper function of HSCs several regulatory mechanisms are in place. The microenvironment in which HSCs reside provides soluble factors and cell-cell interactions. In the cell-nucleus, these cell-extrinsic cues are interpreted in the context of cell-intrinsic developmental programs which are governed by transcription factors. An essential transcription factor for initiation of hematopoiesis is Scl/Tal1 (stem cell leukemia gene/T-cell acute leukemia gene 1). Loss of Scl results in early embryonic death and total lack of all blood cells, yet deactivation of Scl in the adult does not affect HSC function (Mikkola et al., 2003b. In order to define the temporal window of Scl requirement during fetal hematopoietic development, we deactivated Scl in all hematopoietic lineages shortly after hematopoietic specification in the embryo . Interestingly, maturation, expansion and function of fetal HSCs was unaffected, and, as in the adult, red blood cell and platelet differentiation was impaired (Paper III)(Schlaeger et al., 2005). These findings highlight that, once specified, the hematopoietic fate is stable even in the absence of Scl and is maintained through mechanisms that are distinct from those required for the initial fate choice. As the critical downstream targets of Scl remain unknown, we sought to identify and characterize target genes of Scl (Paper IV). We could identify transcription factor Mef2C (myocyte enhancer factor 2 C) as a novel direct target gene of Scl specifically in the megakaryocyte lineage which largely explains the megakaryocyte defect observed in Scl deficient mice. In addition, we observed an Scl-independent requirement of Mef2C in the B-cell compartment, as loss of Mef2C leads to accelerated B-cell aging (Gekas et al. Submitted). Taken together, these studies identify key extracellular microenvironments and intracellular transcriptional regulators that dictate different stages of HSC development, from emergence to lineage choice to aging.