992 resultados para generaliserade andra
Resumo:
Population dynamics are generally viewed as the result of intrinsic (purely density dependent) and extrinsic (environmental) processes. Both components, and potential interactions between those two, have to be modelled in order to understand and predict dynamics of natural populations; a topic that is of great importance in population management and conservation. This thesis focuses on modelling environmental effects in population dynamics and how effects of potentially relevant environmental variables can be statistically identified and quantified from time series data. Chapter I presents some useful models of multiplicative environmental effects for unstructured density dependent populations. The presented models can be written as standard multiple regression models that are easy to fit to data. Chapters II IV constitute empirical studies that statistically model environmental effects on population dynamics of several migratory bird species with different life history characteristics and migration strategies. In Chapter II, spruce cone crops are found to have a strong positive effect on the population growth of the great spotted woodpecker (Dendrocopos major), while cone crops of pine another important food resource for the species do not effectively explain population growth. The study compares rate- and ratio-dependent effects of cone availability, using state-space models that distinguish between process and observation error in the time series data. Chapter III shows how drought, in combination with settling behaviour during migration, produces asymmetric spatially synchronous patterns of population dynamics in North American ducks (genus Anas). Chapter IV investigates the dynamics of a Finnish population of skylark (Alauda arvensis), and point out effects of rainfall and habitat quality on population growth. Because the skylark time series and some of the environmental variables included show strong positive autocorrelation, the statistical significances are calculated using a Monte Carlo method, where random autocorrelated time series are generated. Chapter V is a simulation-based study, showing that ignoring observation error in analyses of population time series data can bias the estimated effects and measures of uncertainty, if the environmental variables are autocorrelated. It is concluded that the use of state-space models is an effective way to reach more accurate results. In summary, there are several biological assumptions and methodological issues that can affect the inferential outcome when estimating environmental effects from time series data, and that therefore need special attention. The functional form of the environmental effects and potential interactions between environment and population density are important to deal with. Other issues that should be considered are assumptions about density dependent regulation, modelling potential observation error, and when needed, accounting for spatial and/or temporal autocorrelation.
Resumo:
Life-history theory states that although natural selection would favour a maximisation of both reproductive output and life-span, such a combination can not be achieved in any living organism. According to life-history theory the reason for the fact that not all traits can be maximised simultaneously is that different traits compete with each other for resources. These relationships between traits that constrain the simultaneous evolution of two or more traits are called trade-offs. Therefore, during different life-stages an individual needs to optimise its allocation of resources to life-history components such as growth, reproduction and survival. Resource limitation acts on these traits and therefore investment in one trait, e.g. reproduction, reduces the resources available for investment in another trait, e.g. residual reproduction or survival. In this thesis I study how food resources during different stages of the breeding event affect reproductive decisions in the Ural owl (Strix uralensis) and the consequences of these decisions on parents and offspring. The Ural owl is a suitable study species for such studies in natural populations since they are long-lived, site-tenacious, and feed on voles. The vole populations in Fennoscandia fluctuate in three- to four-year cycles, which create a variable food environment for the Ural owls to cope with. The thesis gives new insight in reproductive costs and their consequences in natural animal populations with emphasis on underlying physiological mechanisms. I found that supplementary fed Ural owl parents invest supplemented food resources during breeding in own self-maintenance instead of allocating those resources to offspring growth. This investment in own maintenance instead of improving current reproduction had carry-over effects to the following year in terms of increased reproductive output. Therefore, I found evidence that reduced reproductive costs improves future reproductive performance. Furthermore, I found evidence for the underlying mechanism behind this carry-over effect of supplementary food on fecundity. The supplementary-fed parents reduced their feeding investment in the offspring compared to controls, which enabled the fed female parents to invest the surplus resources in parasite resistance. Fed female parents had lower blood parasite loads than control females and this effect lasted until the following year when also reproductive output was increased. Hence, increased investment in parasite resistance when resources are plentiful has the potential to mediate positive carry-over effects on future reproduction. I further found that this carry-over effect was only present when potentials for future reproduction were good. The thesis also provides new knowledge on resource limitation on maternal effects. I found that increased resources prior to egg laying improve the condition and health of Ural owl females and enable them to allocate more resources to reproduction than control females. These additional resources are not allocated to increase the number of offspring, but instead to improve the quality of each offspring. Fed Ural owl females increased the size of their eggs and allocated more health improving immunological components into the eggs. Furthermore, the increased egg size had long-lasting effects on offspring growth, as offspring from larger eggs were heavier at fledging. Limiting resources can have different short- and long-term consequences on reproductive decisions that affect both offspring number and quality. In long-lived organisms, such as the Ural owl, it appears to be beneficial in terms of fitness to invest in long breeding life-span instead of additional investment in current reproduction. In Ural owls, females can influence the phenotypic quality of the offspring by transferring additional resources to the eggs that can have long-lasting effects on growth.
Resumo:
The actin cytoskeleton is essential for a large variety of cell biological processes. Actin exists in either a monomeric or a filamentous form, and it is very important for many cellular functions that the local balance between these two actin populations is properly regulated. A large number of proteins participate in the regulation of actin dynamics in the cell, and twinfilin, one of the proteins examined in this thesis, belongs to this category. The second level of regulation involves proteins that crosslink or bundle actin filaments, thereby providing the cell with a certain shape. α-Actinin, the second protein studied, mainly acts as an actin crosslinking protein. Both proteins are conserved in organisms ranging from yeast to mammals. In this thesis, the roles of twinfilin and α-actinin in development were examined using Drosophila melanogaster as a model organism. Twinfilin is an actin monomer binding protein that is structurally related to cofilin. In vitro, twinfilin reduces actin polymerisation by sequestering actin monomers. The Drosophila twinfilin (twf) gene was identified and found to encode a protein functionally similar to yeast and mammalian twinfilins. A strong hypomorphic twf mutation was identified, and flies homozygous for this allele were viable and fertile. The adult twf mutant flies displayed reduced viability, a rough eye phenotype and severely malformed bristles. The shape of the adult bristle is determined by the actin bundles that are regularly spaced around the perimeter of the developing pupal bristles. Examination of the twf pupal bristles revealed an increased level of filamentous actin, which in turn resulted in splitting and displacement of the actin bundles. The bristle defect was rescued by twf overexpression in developing bristles. The Twinfilin protein was localised at sites of actin filament assembly, where it was required to limit actin polymerisation. A genetic interaction between twinfilin and twinstar (the gene encoding Cofilin) was detected, consistent with the model predicting that both proteins act to limit the amount of filamentous actin. α-Actinin has been implicated in several diverse cell biological processes. In Drosophila, the only function for α-actinin yet known is in the organisation of the muscle sarcomere. Muscle and non-muscle cells utilise different α-actinin isoforms, which in Drosophila are produced by alternative splicing of a single gene. In this work, novel α-actinin deletion alleles, including ActnΔ233, were generated, which specifically disrupted the transcript encoding the non-muscle α-actinin isoform. Nevertheless, ActnΔ233 homozygous mutant flies were viable and fertile with no obvious defects. By comparing α-actinin protein distribution in wild type and ActnΔ233 mutant animals, it could be concluded that non-muscle α-actinin is the only isoform expressed in young embryos, in the embryonic central nervous system and in various actin-rich structures of the ovarian germline cells. In the ActnΔ233 mutant, α-actinin was detected not only in muscle tissue, but also in embryonic epidermal cells and in certain follicle cell populations in the ovaries. The population of α-actinin protein present in non-muscle cells of the ActnΔ233 mutant is referred to as FC-α-actinin (Follicle Cell). The follicular epithelium in the Drosophila ovary is a well characterised model system for studies on patterning and morphogenesis. Therefore, α-actinin expression, regulation and function in this tissue were further analysed. Examination of the α-actinin localisation pattern revealed that the basal actin fibres of the main body follicle cells underwent an organised remodelling during the final stages of oogenesis. This involved the assembly of a transient adhesion site in the posterior of the cell, in which α-actinin and Enabled (Ena) accumulated. Follicle cells genetically manipulated to lack all α-actinin isoforms failed to remodel their cytoskeleton and translocate Ena to the posterior of the cell, while the actin fibres as such were not affected. Neither was epithelial morphogenesis disrupted. The reorganisation of the basal actin cytoskeleton was also disturbed following ectopic expression of Decapentaplegic (Dpp) or as a result of a heat shock. At late oogenesis, the main body follicle cells express both non-muscle α-actinin and FC-α-actinin, while the dorsal anterior follicle cells express only non-muscle α-actinin. The dorsal anterior cells are patterned by the Dpp and Epidermal growth factor receptor (EGFR) signalling pathways, and they will ultimately secrete the dorsal appendages of the egg. Experiments involving ectopic activation of EGFR and Dpp signalling showed that FC-α-actinin is negatively regulated by combined EGFR and Dpp signalling. Ubiquitous overexpression of the adult muscle-specific α-actinin isoform induced the formation of aberrant actin bundles in migrating follicle cells that did not normally express FC-α-actinin, provided that the EGFR signalling pathway was activated in the cells. Taken together, this work contributes new data to our knowledge of α-actinin function and regulation in Drosophila. The cytoskeletal remodelling shown to depend on α-actinin function provides the first evidence that α-actinin has a role in the organisation of the cytoskeleton in a non-muscle tissue. Furthermore, the cytoskeletal remodelling constitutes a previously undescribed morphogenetic event, which may provide us with a model system for in vivo studies on adhesion dynamics in Drosophila.
Resumo:
Increased anthropogenic loading of nitrogen (N) and phosphorus (P) has led to an eutrophication problem in the Baltic Sea, and the spring bloom is a key component in the biological uptake of increased nutrient concentrations. The spring bloom in the Baltic Sea is dominated by both diatoms and dinoflagellates. However, the sedimentation of these groups is different: diatoms tend to sink to the sea floor at the end of the bloom, while dinoflagellates to a large degree are been remineralized in the euphotic zone. Understanding phytoplankton competition and species specific ecological strategies is thus of importance for assessing indirect effects of phytoplankton community composition on eutrophication problems. The main objective of this thesis was to describe some basic physiological and ecological characteristics of the main cold-water diatoms and dinoflagellates in the Baltic Sea. This was achieved by specific studies of: (1) seasonal vertical positioning, (2) dinoflagellate life cycle, (3) mixotrophy, (4) primary production, respiration and growth and (5) diatom silicate uptake, using cultures of common cold-water diatoms: Chaetoceros wighamii, C. gracilis, Pauliella taeniata, Thalassiosira baltica, T. levanderi, Melosira arctica, Diatoma tenuis, Nitzschia frigida, and dinoflagellates: Peridiniella catenata, Woloszynskia halophila and Scrippsiella hangoei. The diatoms had higher primary production capacity and lower respiration rate compared with the dinoflagellates. This difference was reflected in the maximum growth rate, which for the examined diatoms range from 0.6 to 1.2 divisions d-1, compared with 0.2 to 0.3 divisions d-1 for the dinoflagellates. Among diatoms there were species specific differences in light utilization and uptake of silicate, and C. wighamii had the highest carbon assimilation capacity and maximum silicate uptake. The physiological properties of diatoms and dinoflagellates were used in a model of the onset of the spring bloom: for the diatoms the model could predict the initiation of the spring bloom; S. hangoei, on the other hand, could not compete successfully and did not obtain positive growth in the model. The other dinoflagellates did not have higher growth rates or carbon assimilation rates and would thus probably not perform better than S. hangoei in the model. The dinoflagellates do, however, have competitive advantages that were not included in the model: motility and mixotrophy. Previous investigations has revealed that the chain-forming P. catenata performs diurnal vertical migration (DVM), and the results presented here suggest that active positioning in the water column, in addition to DVM, is a key element in this species' life strategy. There was indication of mixotrophy in S. hangoei, as it produced and excreted the enzyme leucine aminopeptidase (LAP). Moreover, there was indirect evidence that W. halophila obtains carbon from other sources than photosynthesis when comparing increase in cell numbers with in situ carbon assimilation rates. The results indicate that mixotrophy is a part of the strategy of vernal dinoflagellates in the Baltic Sea. There were also indications that the seeding of the spring bloom is very important for the dinoflagellates to succeed. In mesocosm experiments dinoflagellates could not compete with diatoms when their initial numbers were low. In conclusion, this thesis has provided new information about the basic physiological and ecological properties of the main cold-water phytoplankton in the Baltic Sea. The main phytoplankton groups, diatoms and dinoflagellates, have different physiological properties, which clearly separate their life strategies. The information presented here could serve as further steps towards better prognostic models of the effects of eutrophication in the Baltic Sea.
Resumo:
Herbivorous insects comprise a major part of terrestrial biodiversity, and their interactions with their host plants and natural enemies are of vast ecological importance. A large body of research demonstrates that the ecology and evolution of these insects may be affected by trophic interactions, by abiotic influences, and by intraspecific processes, but so far research on these individual aspects has rarely been combined. This thesis uses the leaf-mining moth Tischeria ekebladella and the pedunculate oak (Quercus robur) as a case study to assess how spatial variation in trophic interactions and the physical distribution of host trees jointly affect the distribution, dynamics and evolution of a host-specific herbivore. With respect to habitat quality, Tischeria ekebladella experiences abundant variation at several spatial scales. Most of this variation occurs at small scales notably among leaves and shoots within individual trees. While hypothetically this could cause moths to evolve an ability to select leaves and shoots of high quality, I did not find any coupling between female preference and offspring performance. Based on my studies on temporal variation in resource quality I therefore propose that unpredictable temporal changes in the relative rankings of individual resource units may render it difficult for females to predict the fate of their developing offspring. With respect to intraspecific processes, my results suggest that limited moth dispersal in relation to the spatial distribution of oak trees plays a key role in determining the regional distribution of Tischeria ekebladella. The distribution of the moth is aggregated at the landscape level, where local leaf miner populations are less likely to be present where oaks are scarce. A modelling exercise based on empirical dispersal estimates revealed that the moth population on Wattkast an island in south-western Finland is spatially structured overall, but that the relative importance of local and regional processes on tree-specific moth dynamics varies drastically across the landscape. To conclude, my work in the oak-Tischeria ekebladella system demonstrates that the local abundance and regional distribution of a herbivore may be more strongly influenced by the spatial location of host trees than by their relative quality. Hence, it reveals the importance of considering spatial context in the study of herbivorous insects, and forms a bridge between the classical fields of plant-insect interactions and spatial ecology.
Resumo:
Interactions among individuals give rise to both cooperation and conflict. Individuals will behave selfishly or altruistically depending on which gives the higher payoff. The reproductive strategies of many animals are flexible and several alternative tactics may be present from which the most suitable one is applied. Generally, alternative reproductive tactics may be defined as a response to competition from individuals of the same sex. These alternative reproductive tactics are means by which individuals may fine-tune their fitness to the reigning circumstances and which are shaped by the environment individuals are occupying as well as by the behaviour of other individuals sharing the environment. By employing such alternative ways of achieving reproductive output, individuals may alleviate competition from others. Conspecific brood parasitism (CBP) is an alternative reproductive strategy found in several egg laying animal groups, and it is especially common among waterfowl. Within this alternative reproductive strategy, four reproductive options can be identified. These four options represent a continuum from low reproductive effort coupled with low fitness returns, to high reproductive effort and consequently high benefits. It may not be evident how individuals should allocate reproductive effort between eggs laid in their own nest vs. in nests of others, however. Limited fecundity will constrain the number of eggs donated by a parasite, but also the tendency for hosts to accept parasitic eggs may affect the allocation decision. Furthermore, kinship, individual quality and the costs of breeding may play a role in complicating the allocation decision. In this thesis, I view the seemingly paradoxical effects of kinship on conflict resolution in the context of alternative reproductive tactics, examining the resulting features of cooperation and conflict. Conspecific brood parasitism sets the stage for investigating these questions. By using both empirical and theoretical approaches, I examine the nature of CBP in a brood parasitic duck, the Barrow's goldeneye (Bucephala islandica). The theoretical chapter of this thesis gives rise to four main conclusions. Firstly, variation in individual quality plays a central role in shaping breeding strategies. Secondly, kinship plays a central role in the evolution of CBP. Thirdly, egg recognition ability may affect the prevalence of parasitism. If egg recognition is perfect, higher relatedness between host and parasite facilitates CBP. Finally, I show that the relative costs of egg laying and post-laying care play a so far underestimated role in determining the prevalence of parasitism. The costs of breeding may outweigh possible inclusive fitness benefits accrued from receiving eggs from relatives. Several of the patterns brought out by the theoretical work are then confirmed empirically in the following chapters. Findings include confirmation of the central role of relatedness in determining the extent of parasitism as well as inducing a counterintuitive host clutch reduction. Furthermore, I demonstrate a cost of CBP inflicted on hosts, as well as results suggesting that host age reflects individual quality, affecting the ability to overcome costs inflicted by CBP. In summary, I demonstrate both theoretically and empirically the presence of cooperation and conflict in the interactions between conspecific parasites and their hosts. The field of CBP research has traditionally been divided, but the first steps have now been taken toward the acceptance of the opposite side of the divide. Especially the theoretical findings of chapter 1 offer the possibility to view seemingly contrasting results of various studies within the same framework, and may direct future research toward more general features underlying differences in the patterns of CBP between populations or species.
Resumo:
Social groups are common across animal species. The reasons for grouping are straightforward when all individuals gain directly from cooperating. However, the situation becomes more complex when helping entails costs to the personal reproduction of individuals. Kin selection theory has offered a fruitful framework to explain such cooperation by stating that individuals may spread their genes not only through their own reproduction, but also by helping related individuals reproduce. However, kin selection theory also implicitly predicts conflicts when groups consist of non-clonal individuals, i.e. relatedness is less than one. Then, individual interests are not perfectly aligned, and each individual is predicted to favour the propagation of their own genome over others. Social insects provide a solid study system to study the interplay between cooperation and conflict. Breeding systems in social insects range from solitary breeding to eusocial colonies displaying complete division of reproduction between the fertile queen and the sterile worker caste. Within colonies, additional variation is provided by the presence of several reproductive individuals. In many species, the queen mates multiply, which causes the colony to consist of half-sib instead of full-sib offspring. Furthermore, in many species colonies contain multiple breeding queens, which further dilutes relatedness between colony members. Evolutionary biology is thus faced with the challenge to answer why such variation in social structure exists, and what the consequences are on the individual and population level. The main part of this thesis takes on this challenge by investing the dynamics of socially polymorphic ant colonies. The first four chapters investigate the causes and consequences of different social structures, using a combination of field studies, genetic analyses and laboratory experiments. The thesis ends with a theoretical chapter focusing on different social interactions (altruism and spite), and the evolution of harming traits. The main results of the thesis show that social polymorphism has the potential to affect the behaviour and traits of both individuals and colonies. For example, we found that genetic polymorphism may increase the phenotypic variation between individuals in colonies, and that socially polymorphic colonies may show different life history patterns. We also show that colony cohesion may be enhanced even in multiple-queen colonies through patterns of unequal reproduction between queens. However, the thesis also demonstrates that spatial and temporal variation between both populations and environments may affect individual and colony traits, to the degree that results obtained in one place or at one time may not be applicable in other situations. This opens up potential further areas of research to explain these differences.
Resumo:
With transplant rejection rendered a minor concern and survival rates after liver transplantation (LT) steadily improving, long-term complications are attracting more attention. Current immunosuppressive therapies, together with other factors, are accompanied by considerable long-term toxicity, which clinically manifests as renal dysfunction, high risk for cardiovascular disease, and cancer. This thesis investigates the incidence, causes, and risk factors for such renal dysfunction, cardiovascular risk, and cancer after LT. Long-term effects of LT are further addressed by surveying the quality of life and employment status of LT recipients. The consecutive patients included had undergone LT at Helsinki University Hospital from 1982 onwards. Data regarding renal function – creatinine and estimated glomerular filtration rate (GFR) – were recorded before and repeatedly after LT in 396 patients. The presence of hypertension, dyslipidemia, diabetes, impaired fasting glucose, and overweight/obesity before and 5 years after LT was determined among 77 patients transplanted for acute liver failure. The entire cohort of LT patients (540 patients), including both children and adults, was linked with the Finnish Cancer Registry, and numbers of cancers observed were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, gender, and calendar time. Health-related quality of life (HRQoL), measured by the 15D instrument, and employment status were surveyed among all adult patients alive in 2007 (401 patients). The response rate was 89%. Posttransplant cardiovascular risk factor prevalence and HRQoL were compared with that in the age- and gender-matched Finnish general population. The cumulative risk for chronic kidney disease increased from 10% at 5 years to 16% at 10 years following LT. GFR up to 10 years after LT could be predicted by the GFR at 1 year. In patients transplanted for chronic liver disease, a moderate correlation of pretransplant GFR with later GFR was also evident, whereas in acute liver failure patients after LT, even severe pretransplant renal dysfunction often recovered. By 5 years after LT, 71% of acute liver failure patients were receiving antihypertensive medications, 61% were exhibiting dyslipidemia, 10% were diabetic, 32% were overweight, and 13% obese. Compared with the general population, only hypertension displayed a significantly elevated prevalence among patients – 2.7-fold – whereas patients exhibited 30% less dyslipidemia and 71% less impaired fasting glucose. The cumulative incidence of cancer was 5% at 5 years and 13% at 10. Compared with the general population, patients were subject to a 2.6-fold cancer risk, with non-melanoma skin cancer (standardized incidence ratio, SIR, 38.5) and non-Hodgkin lymphoma (SIR 13.9) being the predominant malignancies. Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy raised skin-cancer risk. HRQoL deviated clinically unimportantly from the values in the general population, but significant deficits among patients were evident in some physical domains. HRQoL did not seem to decrease with longer follow-up. Although 87% of patients reported improved working capacity, data on return to working life showed marked age-dependency: Among patients aged less than 40 at LT, 70 to 80% returned to work, among those aged 40 to 50, 55%, and among those above 50, 15% to 28%. The most common cause for unemployment was early retirement before LT. Those patients employed exhibited better HRQoL than those unemployed. In conclusion, although renal impairment, hypertension, and cancer are evidently common after LT and increase with time, patients’ quality of life remains comparable with that of the general population.
Resumo:
Exposure to water-damaged buildings and the associated health problems have evoked concern and created confusion during the past 20 years. Individuals exposed to moisture problem buildings report adverse health effects such as non-specific respiratory symptoms. Microbes, especially fungi, growing on the damp material have been considered as potential sources of the health problems encountered in these buildings. Fungi and their airborne fungal spores contain allergens and secondary metabolites which may trigger allergic as well as inflammatory types of responses in the eyes and airways. Although epidemiological studies have revealed an association between damp buildings and health problems, no direct cause-and-effect relationship has been established. Further knowledge is needed about the epidemiology and the mechanisms leading to the symptoms associated with exposure to fungi. Two different approaches have been used in this thesis in order to investigate the diverse health effects associated with exposure to moulds. In the first part, sensitization to moulds was evaluated and potential cross-reactivity studied in patients attending a hospital for suspected allergy. In the second part, one typical mould known to be found in water-damaged buildings and to produce toxic secondary metabolites was used to study the airway responses in an experimental model. Exposure studies were performed on both naive and allergen sensitized mice. The first part of the study showed that mould allergy is rare and highly dependent on the atopic status of the examined individual. The prevalence of sensitization was 2.7% to Cladosporium herbarum and 2.8% to Alternaria alternata in patients, the majority of whom were atopic subjects. Some of the patients sensitized to mould suffered from atopic eczema. Frequently the patients were observed to possess specific serum IgE antibodies to a yeast present in the normal skin flora, Pityrosporum ovale. In some of these patients, the IgE binding was partly found to be due to binding to shared glycoproteins in the mould and yeast allergen extracts. The second part of the study revealed that exposure to Stachybotrys chartarum spores induced an airway inflammation in the lungs of mice. The inflammation was characterized by an influx of inflammatory cells, mainly neutrophils and lymphocytes, into the lungs but with almost no differences in airway responses seen between the satratoxin producing and non-satratoxin producing strain. On the other hand, when mice were exposed to S. chartarum and sensitized/challenged with ovalbumin the extent of the inflammation was markedly enhanced. A synergistic increase in the numbers of inflammatory cells was seen in BAL and severe inflammation was observed in the histological lung sections. In conclusion, the results in this thesis imply that exposure to moulds in water damaged buildings may trigger health effects in susceptible individuals. The symptoms can rarely be explained by IgE mediated allergy to moulds. Other non-allergic mechanisms seem to be involved. Stachybotrys chartarum is one of the moulds potentially responsible for health problems. In this thesis, new reaction models for the airway inflammation induced by S. chartarum have been found using experimental approaches. The immunological status played an important role in the airway inflammation, enhancing the effects of mould exposure. The results imply that sensitized individuals may be more susceptible to exposure to moulds than non-sensitized individuals.
Resumo:
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.
Resumo:
Background: As the human body ages, the arteries gradually lose their elasticity and become stiffer. Although inevitable, this process is influenced by hereditary and environmental factors. Interestingly, many classic cardiovascular risk factors affect the arterial stiffness. During the last decade, accelerated arterial stiffening has been recognized as an important cardiovascular risk factor associated with increased mortality as well as with several chronic disorders. Objectives: This thesis examines the role of arterial stiffness in relation to variations in a physiological feature in healthy individuals. In addition, the effect on arterial stiffness of an acute transitory disease and the effect of a chronic disease are studied. Furthermore, the thesis analyzes the prognostic value of a marker of arterial stiffness in individuals with chronic disease. Finally, a potential method of reducing arterial stiffness is evaluated. Material and study design: The first study examines pulse wave reflection and pulse wave velocity in relation to muscle fibre distribution in healthy middle-aged men. In the second study, pulse wave reflection in women with current or previous preeclampsia is compared to a healthy control group. The effect of aging on the different blood pressure indices in patients with type 1 diabetes is examined in the third study, whereas the fourth paper studies the relation between these blood pressure indices and mortality in type 2 diabetes. The fifth study evaluates how intake of a fermented milk product containing bioactive peptides affects pulse wave reflection in individuals with mild hypertension. Results and conclusions: Muscle fibre type distribution is not an independent determinant of arterial stiffness in middle-aged males. Pulse wave reflection is increased in pregnant women with preeclampsia, but not in previously preeclamptic non-pregnant women. Patients with type 1 diabetes have a higher and more rapidly increasing pulse pressure, which suggests accelerated arterial stiffening. In elderly type 2 diabetic patients, very high and very low levels of pulse pressure are associated with higher mortality. Intake of milk-derived bioactive peptides reduces pulse wave reflection in hypertensive males but not in hypertensive females.
Resumo:
The output of a laser is a high frequency propagating electromagnetic field with superior coherence and brightness compared to that emitted by thermal sources. A multitude of different types of lasers exist, which also translates into large differences in the properties of their output. Moreover, the characteristics of the electromagnetic field emitted by a laser can be influenced from the outside, e.g., by injecting an external optical field or by optical feedback. In the case of free-running solitary class-B lasers, such as semiconductor and Nd:YVO4 solid-state lasers, the phase space is two-dimensional, the dynamical variables being the population inversion and the amplitude of the electromagnetic field. The two-dimensional structure of the phase space means that no complex dynamics can be found. If a class-B laser is perturbed from its steady state, then the steady state is restored after a short transient. However, as discussed in part (i) of this Thesis, the static properties of class-B lasers, as well as their artificially or noise induced dynamics around the steady state, can be experimentally studied in order to gain insight on laser behaviour, and to determine model parameters that are not known ab initio. In this Thesis particular attention is given to the linewidth enhancement factor, which describes the coupling between the gain and the refractive index in the active material. A highly desirable attribute of an oscillator is stability, both in frequency and amplitude. Nowadays, however, instabilities in coupled lasers have become an active area of research motivated not only by the interesting complex nonlinear dynamics but also by potential applications. In part (ii) of this Thesis the complex dynamics of unidirectionally coupled, i.e., optically injected, class-B lasers is investigated. An injected optical field increases the dimensionality of the phase space to three by turning the phase of the electromagnetic field into an important variable. This has a radical effect on laser behaviour, since very complex dynamics, including chaos, can be found in a nonlinear system with three degrees of freedom. The output of the injected laser can be controlled in experiments by varying the injection rate and the frequency of the injected light. In this Thesis the dynamics of unidirectionally coupled semiconductor and Nd:YVO4 solid-state lasers is studied numerically and experimentally.
Resumo:
Black hole X-ray binaries, binary systems where matter from a companion star is accreted by a stellar mass black hole, thereby releasing enormous amounts of gravitational energy converted into radiation, are seen as strong X-ray sources in the sky. As a black hole can only be detected via its interaction with its surroundings, these binary systems provide important evidence for the existence of black holes. There are now at least twenty cases where the measured mass of the X-ray emitting compact object in a binary exceeds the upper limit for a neutron star, thus inferring the presence of a black hole. These binary systems serve as excellent laboratories not only to study the physics of accretion but also to test predictions of general relativity in strongly curved space time. An understanding of the accretion flow onto these, the most compact objects in our Universe, is therefore of great importance to physics. We are only now slowly beginning to understand the spectra and variability observed in these X-ray sources. During the last decade, a framework has developed that provides an interpretation of the spectral evolution as a function of changes in the physics and geometry of the accretion flow driven by a variable accretion rate. This doctoral thesis presents studies of two black hole binary systems, Cygnus~X-1 and GRS~1915+105, plus the possible black hole candidate Cygnus~X-3, and the results from an attempt to interpret their observed properties within this emerging framework. The main result presented in this thesis is an interpretation of the spectral variability in the enigmatic source Cygnus~X-3, including the nature and accretion geometry of its so-called hard spectral state. The results suggest that the compact object in this source, which has not been uniquely identified as a black hole on the basis of standard mass measurements, is most probably a massive, ~30 Msun, black hole, and thus the most massive black hole observed in a binary in our Galaxy so far. In addition, results concerning a possible observation of limit-cycle variability in the microquasar GRS~1915+105 are presented as well as evidence of `mini-hysteresis' in the extreme hard state of Cygnus X-1.
Resumo:
Nucleation is the first step of the process by which gas molecules in the atmosphere condense to form liquid or solid particles. Despite the importance of atmospheric new-particle formation for both climate and health-related issues, little information exists on its precise molecular-level mechanisms. In this thesis, potential nucleation mechanisms involving sulfuric acid together with either water and ammonia or reactive biogenic molecules are studied using quantum chemical methods. Quantum chemistry calculations are based on the numerical solution of Schrödinger's equation for a system of atoms and electrons subject to various sets of approximations, the precise details of which give rise to a large number of model chemistries. A comparison of several different model chemistries indicates that the computational method must be chosen with care if accurate results for sulfuric acid - water - ammonia clusters are desired. Specifically, binding energies are incorrectly predicted by some popular density functionals, and vibrational anharmonicity must be accounted for if quantitatively reliable formation free energies are desired. The calculations reported in this thesis show that a combination of different high-level energy corrections and advanced thermochemical analysis can quantitatively replicate experimental results concerning the hydration of sulfuric acid. The role of ammonia in sulfuric acid - water nucleation was revealed by a series of calculations on molecular clusters of increasing size with respect to all three co-ordinates; sulfuric acid, water and ammonia. As indicated by experimental measurements, ammonia significantly assists the growth of clusters in the sulfuric acid - co-ordinate. The calculations presented in this thesis predict that in atmospheric conditions, this effect becomes important as the number of acid molecules increases from two to three. On the other hand, small molecular clusters are unlikely to contain more than one ammonia molecule per sulfuric acid. This implies that the average NH3:H2SO4 mole ratio of small molecular clusters in atmospheric conditions is likely to be between 1:3 and 1:1. Calculations on charged clusters confirm the experimental result that the HSO4- ion is much more strongly hydrated than neutral sulfuric acid. Preliminary calculations on HSO4- NH3 clusters indicate that ammonia is likely to play at most a minor role in ion-induced nucleation in the sulfuric acid - water system. Calculations of thermodynamic and kinetic parameters for the reaction of stabilized Criegee Intermediates with sulfuric acid demonstrate that quantum chemistry is a powerful tool for investigating chemically complicated nucleation mechanisms. The calculations indicate that if the biogenic Criegee Intermediates have sufficiently long lifetimes in atmospheric conditions, the studied reaction may be an important source of nucleation precursors.
Resumo:
Varttuminen vietnamilaisena Suomessa: 12 vuoden seurantajakso – Vietnamilaisten hyvinvointi ja sosiokulttuurinen sopeutuminen lapsena/nuorena sekä nuorena aikuisena Tämä tutkimus oli määrällinen pitkittäistutkimus lapsena tai nuorena vuosina 1979-1991 Suomeen saapuneiden vietnamilaisten akkulturaatiosta (kulttuurin muutoksista), psyykkisestä hyvinvoinnista ja sosiokulttuurisesta sopeutumisesta. Tutkimukseen osallistui ensimmäisessä vaiheessa (vuonna 1992) 97 satunnaisesti valittua vietnamilaista peruskoululaista ympäri maata, joita verrattin suomalaisiin luokkatovereihin. Seurantavaiheeseen (vuonna 2004) osallistui 59 ensimmäisessä vaiheessa mukana ollutta vietnamilaista, nyt iältään 20 – 31 -vuotiaita. Tutkimuksen tavoitteena oli selvittää mitkä tekijät ennustivat akkulturaation lopputuloksia, samalla huomioiden iän ja ympäristön (kontekstin) vaikutukset psyykkiseen hyvinvointiin ja sosiokulttuuriseen sopeutumiseen. Yksittäiset akkulturaatiodimensiot (kieli, arvot ja identiteetti) osoittautuivat tärkeämmiksi psyykkiselle hyvinvoinnille ja sosiokulttuuriselle sopeutumiselle kuin etniset, kansalliset tai kaksikulttuuriset profiilit, joissa yhdistyivät ao. kieli, arvot ja identiteetti. Identiteettimuutosta tapahtui (etniseen) vietnamilaiseen suuntaan ajan kuluessa, kun taas arvomuutosta tapahtui (kansalliseen) suomalaiseen suuntaan. Sekä suomen että vietnamin kielen taito lisääntyivät ajan myötä, millä oli myönteisiä vaikutuksia sekä psyykkiseen hyvinvointiin että sosiokulttuuriseen sopeutumiseen. Lähtötilanteen psyykkinen hyvinvointi ennusti hyvinvointia (masennuksen puutetta ja itsetuntoa) aikuisena, mutta sosiokulttuurinen sopeutuminen (koulumenestys) lapsena tai nuorena ei ennustanut kouluttautumista aikuisena. Parempi suomen kielen taito ja vähemmän identifioitumista suomalaiseksi aikuisena sekä masentuneisuuden puute ja vähemmän koettua syrjintää lapsena tai nuorena erottelivat psyykkisesti paremmin voivat aikuiset (ei-masentuneet) heistä, jotka olivat masentuneita. Parempaa kouluttautumista aikuisena ennustivat toisaalta vähemmän koettua syrjintää lapsena tai nuorena ja toisaalta aikuisena parempi suomen kielen taito, suurempi kansallisten (suomalaisten) itsenäisyysarvojen kannattaminen, mutta kuitenkin vähemmän identifioitumista suomalaisiin. Koetun syrjinnän merkitys psyykkiselle hyvinvoinnille, erityisesti lapsena tai nuorena, sekä sen pitkäaikaisvaikutukset psyykkiselle hyvinvoinnille ja sosiokulttuuriselle sopeutumiselle aikuisena osoittavat tarpeen puuttua varhain psyykkisiin ongelmiin sekä parantaa etnisten ryhmien välisiä suhteita. Avainsanat: akkulturaatio, psyykkinen hyvinvointi, sosiokultuurinen sopeutuminen, kieli, arvot, identiteetti, vietnamilainen, Suomi, lapset, nuoret, nuoret aikuiset