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  • Kähkönen, Mika A. (Helsingin yliopisto, 2003)
  • Auvinen, Ari-Pekka (Helsingin yliopisto, 2006)
    The goal of this study has been to compile and to further develop a collection of biodiversity indicators for Finland. Biodiversity indicators aim at bringing forth information related to biodiversity change and the factors causing it in a condensed and easy to understand manner. The factual information which indicators provide is supposed to appeal to the reader's intellect and thus to have an influence on her opinions and behavior. Biodiversity indicators also aim at influencing biodiversity related politics. Being successful at this, biodiversity indicators can make a strong contribution towards reaching the most important goal of nature conservation the perpetuation of natural variety. The study is divided into two parts. The first part presents a preliminary collection of 75 biodiversity indicators. These indicators are based on the biodiversity monitoring and research data as well as other statistical data which were readily available at the time of their composition. In addition to the statistics and literature reviewed the study is based on interviews of numerous experts. The collection of 75 biodiversity indicators enables a reasonably comprehensive assessment of the major factors effect-ing biodiversity as well as of the state and development of some components of biodiversity (e.g. endangered species). It, however, contains too few indicators on the state and development of common species and on many important characteristics of ecosystems. The data for such indicators were not available. The second part of the study consists of a review of some European national biodiversity monitoring schemes, international biodiversity indicator development projects as well as Finnish national biodiversity monitoring field programs. Based on the review, recommendations for the further development of the indicator based biodiversity information system are made. The second part of the study concludes with a proposal for an expanded biodiversity indicator collection which contains 31 new indicators. The expanded biodiversity indicator collection could provide a sound factual foundation on which comprehensive assessments of state and development of biodiversity could be based. Such assessments are needed when the effects of biodiversity related politics are evaluated and decisions concerning where to focus conservation efforts are made. At the end of this study possible applications of the expanded biodiversity indicator collection are examined in the light of four different conservation objectives
  • Söderman, Tarja (Helsingin yliopisto, 2012)
    Ecological impact assessment focuses both on spatially bound biophysical environment and biodiversity as composition, structure, and key processes and on benefits of biodiversity gained through ecosystem services. It deals with allocation of space in complex situations characterised by uncertainty and conflicting values of actors. In the process of ecological impact assessment that forms part of environmental impact assessment (EIA) and strategic environmental assessment (SEA), the whole proposal of a project, plan, or programme; its targets; alternative options and their acceptability from a biodiversity standpoint; and knowledge of the biodiversity and ecosystem services it provides are shaped. The analyses in this thesis examine the current practices of Finnish ecological impact assessment with respect to its substantive and procedural features and the roles of actors. The analyses utilise qualitative and semi-quantitative data from EIA and Natura 2000 appropriate assessment reports, statements of environmental authorities, other data produced via assessment processes, and actors views related to ecological impact assessment. After analysis of the present shortcomings, constraints, and development needs, a tool taking into account fully current understanding and ecosystem services is developed to improve prevailing impact assessment practices. The results of the analyses demonstrate that the knowledge base for the comprehensive ecological impact assessment in EIA, Natura 2000 appropriate assessment, and municipal land-use planning SEA is far from adequate. Impact assessments fail to identify the biodiversity at stake, what is affected, and how, and, as a consequence, the selection of biodiversity elements for assessment is unsystematic, superficial, or focused on the most obvious strictly protected species. The connection between baseline studies and impact prediction is loose; consequently, the predictive value of baseline studies is low, preventing effective mitigation and monitoring. There is also a tendency toward unnecessary detail at the expense of a broader treatment of biodiversity that would address ecosystem processes, interactions, and trends. Substantive treatment of biodiversity is often restricted to compositional diversity and at the species and habitat type level. Finnish ecological impact assessment does not take into account the value-laden nature of impact assessment. It is baseline-oriented and often seen as external and parallel to the actual planning and decision-making. Scoping practices reflect this separateness by outsourcing important value-bound significance determinations to individual ecology consultants instead of considering them an integral part of the planning process. Cumulative effects are hardly ever considered in Finnish ecological impact assessment practices. The use of more sophisticated methods and tools than expert judgements and matrices is almost non-existent in Finnish ecological impact assessment practices, because of the planning environment lacking the time, resources, and skills for it. In addition, often a highly detailed treatment of biodiversity elements with complex tools is not necessary for achieving a holistic picture of the targets and impacts of an initiative. Therefore, an objective set for improvement in the knowledge grounding of ecological impact assessment has been the development of a relatively simple tool utilising already available data. Ecosystem services criteria and indicators were developed for target-setting, impact prediction, and monitoring, and these were tested in three processes of local master planning and regional planning. Timing constraints of data delivery; obstacles in data availability, quality, and consistency; and relative closeness of planning processes hampered the use of indicators, but the tool nonetheless was experienced as beneficial by the testing teams overall. The future challenges facing use of the tool involve its independent utilisation by planners without support from researchers on different planning scales, collaboration and commitment of actors in setting targets for ecosystem services, and versatile use of data. The other challenges in improvement of today s ecological impact assessment practices comprise finding a balance between broad-brush and detailed information individually for each planning situation; utilising, sharing, and mediating both knowledge within ecosystem-service-generating units and users and beneficiaries views of valued and prioritised ecosystem services; shifting from parallel linkage of impact assessment and planning towards planning- and decision-making-centred environmental assessment; supplying the necessary substantive and procedural requirements for ecological impact assessment in the EIA, nature conservation, and land-use and building legislation; placing stronger emphasis on scoping by strengthening the guiding role of authorities and reserving more time and resources for scoping by proponents and planners; generating specific cumulative impact assessment in EIA and SEA and improving that employed in Natura 2000 appropriate assessment by creating an iterative link; and fostering work-sharing between project- and plan/programme-level actors in identification of cumulative impacts.
  • Wacklin, Pirjo (Helsingin yliopisto, 2006)
    Currently, the classification used for cyanobacteria is based mainly on morphology. In many cases the classification is known to be incongruent with the phylogeny of cyanobacteria. The evaluation of this classification is complicated by the fact that numerous strains are only described morphologically and have not been isolated. Moreover, the phenotype of many cyanobacterial strains alters during prolonged laboratory cultivation. In this thesis, cyanobacterial strains were isolated from lakes (mainly Lake Tuusulanjärvi) and both morphology and phylogeny of the isolates were investigated. The cyanobacterial community composition in Lake Tuusulanjärvi was followed for two years in order to relate the success of cyanobacterial phenotypes and genotypes to environmental conditions. In addition, molecular biological methods were compared with traditional microscopic enumeration and their ability and usefulness in describing the cyanobacterial diversity was evaluated. The Anabaena, Aphanizomenon, and Trichormus strains were genetically heterogeneous and polyphyletic. The phylogenetic relationships of the heterocytous cyanobacteria were not congruent with their classification. In contrast to heterocytous cyanobacteria, the phylogenetic relationships of the Snowella and Woronichinia strains, which had not been studied before this thesis, reflected the morphology of strains and followed their current classification. The Snowella strains formed a monophyletic cluster, which was most closely related to the Woronichinia strain. In addition, a new cluster of thin, filamentous cyanobacterial strains identified as Limnothrix redekei was revealed. This cluster was not closely related to any other known cyanobacteria. The cyanobacterial community composition in Lake Tuusulanjärvi was studied with molecular methods [denaturant gradient gel electrophoresis (DGGE) and cloning of the 16S rRNA gene], through enumerations of cyanobacteria under microscope, and by strain isolations. Microcystis, Anabaena/Aphanizomenon, and Synechococcus were the major groups in the cyanobacterial community in Lake Tuusulanjärvi during the two-year monitoring period. These groups showed seasonal succession, and their success was related to different environmental conditions. The major groups of the cyanobacterial community were detected by all used methods. However, cloning gave higher estimates than microscopy for the proportions of heterocytous cyanobacteria and Synechococcus. The differences were probably caused by the high 16S rRNA gene copy numbers in heterotrophic cyanobacteria and by problems in the identification and detection of unicellular cyanobacteria.
  • Eerola, Essi (1999)
    The government must explicitly consider how to value the welfare of different groups in the society when making interventions in order to correct externalities. The welfare effects of government policies create political tensions, which are especially clearly seen in the formation of forest policy. This is because forests are used for timber production, but they are also valuable for other purposes, such as recreation. These different uses are often in conflict, and the trade-off manifests itself in political struggles over the formation of forest policy. In order to address the effects of lobbying on the forest policy, I consider a specific policy issue, namely the conservation of biological diversity in the forests. It is an issue on which forest industry, forest owners and forest activists have very different views concerning the role and responsibility of the government. In my Thesis, I concentrate on two main questions on interest group influence in the context of forest policy, namely to what direction groups affected by the policy seek to push the policy, and what welfare implications successful lobbying has. I analyze the government forest policy in the common agency framework, where an environmental lobby and an industrial lobby simultaneously attempt to influence the decision of the government by offering monetary contributions. To this aim I use the menu auction theory, which I extend to account for the possibility that lobbying is socially costly and that the lobbies are not equally successful in influencing the government. I consider government decision-making in two situations: exported forest product and domestic consumption. The forest industry is represented by a monopoly, and therefore, the conservation affects the price of consumption when the forest product is not exported. The case where the forest industry exports its product thus serves as a useful point of reference when analysing the more diversified case of domestic consumption. Compared to domestic consumption, the government will always choose higher conservation level when the monopoly exports its product and the foreign consumers bear the cost of conservation. Due to non-competitive production sector, it is also possible to analyze how the market power of the industry, determined by the elasticity of demand, influences the government's decision on conservation. The analysis explains why the government's forest policy only partly reflects the normative prescriptions. It also makes explicit that the lobbies indeed have an incentive to cast resources into costly lobbying. In the particular case when the monopoly product is exported and the two lobbies are equally efficient in influencing the government, the political equilibrium coincides with the social optimum. In general, however, lobbying distorts conservation from the socially optimal.
  • Saarikivi, Jarmo (Helsingin yliopisto, 2016)
    Ecologically simplified urban landscapes are often claimed to be useless nature with hardly any wildlife. Golf courses in particular are often claimed to be a poor use of land, ecologically speaking. They cover large areas, have a restricted entrance, are heavily managed and require a lot of resources in their up-keeping. These green deserts and elitist people practicing their sport have been subject to much debate and environmental concern. Populist, active and loud lobbying against the building of golf courses has created a popular opposition, although there is little scientific evidence to support their claims. Therefore, it is of interest to determine to what extent these claims are justified. In this thesis, the ecological value of golf courses was assessed to determine how golf courses contribute to the diversity of open green spaces in an urban setting, by studying the biodiversity of established and newly-created golf courses in the greater Helsinki region, southern Finland. In a series of field experiments, the biodiversity of various animal groups (insects, birds, frogs) with distinct life histories was measured at urban or semi-urban golf courses. Each animal group was used to study different aspects of diversity. Species diversity and assemblages were studied using carabid beetles (articles I, IV), genetic diversity using the common frog (Rana temporaria) (II) and a case study to measure the quality of the golf course environment as habitat was performed using three hole-nesting bird species (great tit, blue tit and pied flycatcher), evaluating their nesting and reproductive success at golf course forest edges (III). Furthermore, the effects of constructing a golf course on carabid beetles were evaluated before (I) and after (IV) course development. Golf courses appeared to be rich in carabid beetle species, very few of them rare or of conservation concern though. Beetle assemblages differed considerably between the golf courses studied and between the habitat types sampled on these courses, but not between course development stages (established vs. newly created vs. reference area). Genetic variation of common frog populations in golf courses showed little differentiation, suggesting that golf courses contribute positively to urban amphibian populations by providing suitable water bodies for reproduction and green corridors for dispersal, thus preventing isolation and loss of genetic variability within populations. Hole-nesting passerine birds showed a clear preference for golf course forest edges over the nearby forests. Birds also performed better in terms of nest occupancy and number of offspring at golf course forest edges, thus indicating a valuable habitat, which could be further improved with the addition of nest boxes. The studies show that golf courses host high biodiversity and have conservation potential in ecologically simplified urban landscapes. Urban fauna seems resilient and capable of adapting to these highly modified environments, thus providing possibilities to enhance biodiversity though the combined and well-planned efforts of various practitioners.
  • Sampolahti, Sani (Helsingfors universitet, 2014)
    In this study the economic values for the breeding goal traits for Finnish Ayrshire cattle were determined by the bioeconomical model. Additionally, the economic value was determined for a new trait, feed efficiency, which was modelled as residual feed intake (RFI). Feed efficiency was added to breeding goals because of intrest in reduction of harmful environmental effects of dairy cattle production. The effect of increasing feed costs on the economic weights was also studied. Economic values were determined by the program ECOWEIGHT. The bioeconomical model included 21 traits, which can be divided a few categories: milk production traits, growth and carcass traits and functional traits (calving difficulty, stillbirth, calf mortality in the rearing period, fertility traits, productive lifetime of cows, incidence of clinical mastitis, somatic cell score (SCS) and residual feed intake (RFI)). Economic values and standardized economic weights were defined for the traits. Profitability of the milk production was negative (?13,3%), when the subsidies were not included in the calculations. Adding RFI didn’t have any effect on the economic values of the other traits and it didn’t change the order of the traits in standardized economical weight. The marginal economic values for RFI of cows and heifers were ?55,8 and ?24,9 €/kg/d, respectively. The highest relative economic weights was found for 305-d milk (36%), protein (14%), fat (9%), mature weight (7%) and calving interval (5%). Relative economic weights for RFI of cows and heifers were 4,6% and 1,5%, respectively. An increase in the feeding costs (10, 30 and 50%) changed the order of the traits in standardized economical weights. The weights of milk production traits were decreased and the weights of growth traits, RFI and calving interval were increased. RFI of cows was the fifth important trait when feeding costs increased 30%. According to the results of this study would be beneficial, especially if the relative im-portance of feed efficiency will increase in the future due to increasing feed costs or in-creasing requirements to mitigate the environmental impact of milk production. However, more research will be needed before adding RFI to the breeding goals.
  • Talvitie, Salla (2014)
    Bakteerit voivat kasvaa plantonisesti eli vapaana nesteessä tai ne voivat kasvaa kiinnittyneenä elolliseen tai elottomaan alustaan. Alustassaan kasvavia mikrobiyhteisöjä kutsutaan biofilmeiksi. Yli 99,9 % bakteereista kasvaa biofilmeissä. Biofilmi muodostuu mikrobeista, joita voi olla yhtä tai useampaa lajia. Bakteerit tuottavat ympärilleen soluväliainetta, joka koostuu erilaisista ekstrasellulaarisista polymeerisistä materiaaleista (EPS) kuten polysakkarideista, proteiineista ja DNA:sta. Biofilmit ovat huomattava ongelma ihmis- ja eläinlääketieteessä, sillä ne ovat osallisena noin 80 %:ssa kaikista ihmisten mikrobiologisissa infektioissa. Biofilmeissä kasvavat bakteerit ovat 10–1000 kertaa resistentimpiä kuin planktoniset bakteerit. Biofilmien resistenssimekanismeja ovat muun muassa heterogeenisyys (monimuotoisuus), lisääntynyt mutaationopeus, antimikrobisia aineita ulospumppaavat pumput ja hidas kasvunopeus. Biofilmit on yhdistetty moniin vaikeasti parannettaviin infektioihin. Eläimillä ne ovat osallisina muun muassa haava- ja vierasesineinfektioiden, osteomyeliitin (luuydintulehdus), utaretulehduksen, keuhkotulehdusten ja monien muiden sairauksien taudinaiheutuksessa. Biofilmien diagnosointi on haastavaa, sillä perinteisillä osoitus- ja hoitomenetelmillä ei saavuteta hyviä tuloksia. Biofilmien diagnosointiin voidaan käyttää mikroskopointia, erilaisia värjäyksiä, viljelymenetelmiä ja DNA-pohjaisia menetelmiä. Näissä kaikissa on omat hyvät ja huonot puolensa. Biofilmien hoito on vaikeaa. Sen vuoksi on tärkeää kyetä ehkäisemään niiden muodostumista. Tärkein keino niiden ehkäisyssä on käyttää hoitotoimenpiteissä aseptisia menetelmiä, jolloin bakteerit eivät pääse kolonisoitumaan. Joskus voidaan käyttää antibiootteja biofilmien muodostuksen ehkäisyyn, sillä planktoniset bakteerit ovat herkkiä antibiooteille toisin kuin biofilmissä kasvavat bakteerit. Antibioottien ehkäisevä käyttö voi kuitenkin suosia resistenttien bakteerikantojen kehittymistä. Vierasesineinfektioiden ehkäisyssä voidaan käyttää erilaisilla antimikrobisilla aineilla päällystettyjä vierasesineitä. Antibiootit eivät ole tehokas keino hoitaa biofilmejä. Niiden hoitoon voidaan käyttää mekaanista poistoa, lääkehunajaa tai erilaisia fysikaalisia menetelmiä kuten ultraääntä
  • Mattila, Katri (Helsingin yliopisto, 2002)
  • Honkala, Juho (Helsingfors universitet, 2014)
    Biochar has been proposed to a promising future product as a carbon sink in carbon sequestration and as a soil conditioner. The aim of this master thesis is to clarify, how biochar affects on the crop formation and yield of faba bean Vicia faba in Southern-Finland. The research includes 3 growing seasons (2010-2012), but the biochar was spred in spring 2010. The study was carried out at the fields of the Viikki research farm, owned by the University Of Helsinki. The study was a split plot experiment, in which as the main plot factor was biochar rate (0, 5, 10 t ha?1). As the sub-plot factor was used fertilizing rate (12, 26 and 40 kg ha?1). To analyzing the yield components, the crop mass samples from the vegetation of every experimental plot were taken. The samples were taken at the end of crop maturation, at the development stage of > 85 (BBCH). Then the samples were dried. The yield components from the samples were separated, such as vegetative (leaves, stalks) and generative parts (pods). After that these parts were weighed. Pods were also calculated and seeds were separated from the pods, and then they were weighed. From obtained data, it was then possible to calculate the key number of yield com-ponents. And finally, the statistical analysis were done with these data. Biochar reduced the plant density at dry growing seasons 2010-2011. But at the same time it enhanced the number of pods per plant and number of seeds per pod. At moist year 2012 there were no significant differences in these components. Biochar didn’t affect significantly on the seed yield of faba bean. Fertilizing didn’t affect significantly on any yield component. Biochar and fertilizing affected significantly together only on 1 000 seeds weight on the year 2010. The lack of statistically significant affects was possibly due to the high fertility of the experimental field. There was evidence that biochar may enhance yield formation of faba bean through the ability of plants to compensate the decreased plant density during dry years. In this situation, a plant in-creases the other yield components. Due to biochar, the tolerance of plants to drought stress can become better. As a conclusion, biochar can be remarkable soil conditioner in the future, in particular during dry growing seasons. However, in fertile soils of Southern-Finland, there are no expected big yield increases in the first three years.
  • Akinrinade, Oyediran (Helsingin yliopisto, 2016)
    Next generation sequencing (NGS) technologies provide the potential for developing high-throughput and low-cost platforms for medical research and diagnostics, which is expected to accelerate the findings of root causes and treatments of human diseases. In addition to short read lengths of NGS technology; another limiting factor to clinical applications of genomic NGS is downstream bioinformatics analysis. Several challenging computation problems have to be solved before we realize the full potential of NGS technology. These include management of large quantities of data, efficient analyses, fusion of data from various sources, and interpretation of identified variants. Endothelial cell (EC) dysfunction is a hallmark of several cardiovascular diseases (CVDs). Loss of functional peroxisome proliferator-activated receptor gamma (PPARγ) leads to EC dysfunction, and development of pulmonary arterial hypertension (PAH). However, the role of PPARγ in angiogenesis in the development of PAH is unknown. In this study, RNA sequencing and bioinformatic strategies were used to quantify and reveal global gene expression changes associated with loss of PPARγ, in a bid to unravel the mechanisms by which PPARγ modulates endothelial homeostasis, regulates angiogenic response, and could contribute to the pathobiology of human cardiovascular diseases. This study reveals, for the first time in an animal model, that loss of PPARγ leads to attenuated ECs migratory capacity and decreased angiogenic potential. Implemented bioinformatics approach revealed a novel molecular mechanism and novel downstream target gene for PPARγ. Furthermore, this study reports the first genetic analysis of dilated cardiomyopathy (DCM) patients in Finland; evaluates the efficacy of NGS in genetic diagnostics of DCM patients, and demonstrates the need for a rigorous and clinically oriented bioinformatics variant assessment and interpretation strategy. In addition, bioinformatics data mining approach was used to evaluate the significance of titin (TTN) truncating variants (TTNtv) in the pathogenesis of DCM. Mutations in genes encoding sarcomere proteins are the leading cause of DCM, with TTNtv accounting for ~21% of DCM cases. Clinical significance of variants in cardiomyopathy-associated genes is difficult to assess due to population genetic variation, and diagnostic yield of genetic testing is not well understood among DCM patients. Moreover, the genetic profile of DCM in Finnish population is poorly understood. In this study, a novel targeted resequencing approach, oligonucleotide-selective sequencing (OS-Seq), was used to investigate the genetic landscape of DCM among Finnish patients, and the approach enabled genetic diagnosis for 35.2% of the patients. Notably, 17.2% of Finnish DCM patients had TTNtv predicted to cause loss of function. Truncating TTN mutations, especially in A-band region, represent the most common cause of DCM. Clinical interpretation of these variants can be challenging, as these variants are also present in reference populations. Meta analyses of TTNtv reported in largest available reference population database, and those identified in accumulated DCM cohorts showed that 50 - 53% of TTNtv in the reference population were located in low transcript count regions, thus, possessing low likelihood of being disease-causing. On this basis, a variant assessment strategy that prioritizes TTNtv affecting at least five transcripts of the gene was developed.
  • Edgren, Henrik (Helsingin yliopisto, 2012)
    Cancer is a disease characterized by the continuous accumulation of somatic cellular aberrations, whether in the DNA or epigenetic changes. During the last decade, many different techniques, including high resolution microarrays as well as exome- and whole genome sequencing, have been developed to comprehensively characterize these changes in cancer cells. In parallel with the development of laboratory techniques, a large variety of bioinformatic methods to analyze data from these have been developed. However, many of these concentrate on the analysis of data from only one laboratory technique, while it is becoming clear that advances in cancer research increasingly depend on integration of multiple different data types for the same tumors. Simultaneously, the recent explosive growth in sequencing data requires the development of new analythical methods. The aim of this thesis was to further characterize the genomic changes in breast cancer, with an emphasis on the development and application of bioinformatic methods to analyze and integrate data from different high throughput analysis techniques. In the first part of this work, the Gene Identification by Nonsense Inhibition method was applied to identify potential tumor suppressor genes in breast cancer. The integration of steady state gene expression, transcript stabilization and array comparative genomic hybridization data for six breast cancer cell lines led to the identification of a nonsense mutation in the RIC8A gene located at 11p15, a region deleted in ~15% of breast tumors. Taken together, our results suggest loss of RIC8A expression may be important in a subgroup of aggressive breast cancers. In study II, we developed a bioinformatic method for highly specific fusion gene identification from paired-end RNA-seq data. Application of the bioinformatic pipeline to data from four breast cancer cell lines led to the identification of 24 novel and three previously published fusion genes, with 95% specificity. In addition to showing that fusion genes are more prevalent in breast cancer than previously thought, several biological characteristics of fusion genes were identified. Most prominently, fusion genes were frequently associated with DNA copy number transitions, particularly high level amplifications, suggesting that most of them are not generated by balanced rearrangements. siRNA knock-down studies furthermore provided evidence for the functional importance of the VAPB-IKZF3 fusion gene in the BT-474 cell line. In the final study, we used aCGH to characterize the size distribution of the ERBB2 amplicon across 71 amplicon carrying tumors and 10 cell lines. To study the possible contribution to cancer of other coamplified genes in the amplicon, 23 genes amplified in 60% of tumors were selected for siRNA screening in two trastuzumab sensitive, two insensitive and one control cell line. In addition to single gene siRNA silencing experiments, five amplicon genes were knocked-down together with ERBB2 to identify synergistic effects. Our results suggest that cancer cells may be dependent on a number of genes in the ERBB2 amplicon besides the primary driver oncogene, a phenomenon termed non-oncogene addiction.
  • Qian, Kui (Helsingin yliopisto, 2013)
    Human papillomaviruses (HPVs) form a large family among double stranded DNA (dsDNA) viruses, some types of which are the major causes of cervical cancer. HPV 16 is widely distributed and the most common high-risk HPV type and approximately half of the cervical cancers are associated with HPV type 16. Of the three HPV 16 encoded oncogenes, the function of E5 in regulating viral replication and pathogenesis is less well understood than E6 and E7. The microRNAs (miRNAs) are important small noncoding RNA molecules that regulate wide range of cellular functions. Some dsDNA viruses, such as SV40 and human polyomaviruses, have functional viral miRNAs. The functional and molecular similarities among dsDNA viruses suggest that HPV could encode viral miRNAs, which have not been validated thus far. The aim of this thesis was to study the functions of the host miRNAs in HPV 16 oncogene induction and identify novel HPV encoded viral miRNAs. We utilized microarray technology to investigate the effect of E5 on host miRNAs and mRNAs expression in 0 96 hours after E5 induction in a cell line model. Among the differentially expressed cellular miRNAs, we further validated the expression of hsa-mir-146a, hsa-mir-203, and hsa-mir-324-5p and some of their target genes in a time series of 96 hours of E5 induction. Our results indicate that HPV E5 expression has an impact through complex regulatory patterns of gene expression in the host cells, and part of those genes is regulated by the E5 protein. Second, high throughput sequencing was used to identify virus-encoded miRNAs. We prepared small RNA sequencing libraries from ten HPV-associated cervical lesions, including cancer and two HPV-harboring cell lines. For more flexible analysis of the sequencing data we developed miRSeqNovel, an R based workflow for miRNA sequencing data analysis, and applied it to the sequencing data to predict putative viral miRNAs and discovered nine putative papillomavirus encoded miRNAs. Viral miRNA validation was performed for five candidates, four of which were successfully validated by qPCR from cervical tissue samples and cell lines: two were encoded by HPV 16, one by HPV 38, and one by HPV 68. The expression of two HPV 16 miRNAs was further supported by in situ hybridization, and colocalization with p16INK4A staining, a marker of cervical neoplasia. Prediction of cellular target genes of HPV 16 encoded miRNAs suggests that they may play a role in cell cycle, immune functions, cell adhesion and migration, development and cancer, which were also among the functions targeted by the E5 regulated host cell mRNA and miRNAs. Two putative viral target sites for the two validated HPV 16 miRNAs were mapped to the E5 gene, one in the E1 gene, two in the L1 gene, and one in the long control region (LCR).
  • Mpindi, John Patrick (Helsingin yliopisto, 2016)
    Bioinformatic tools applied to large-scale genomic and gene expression datasets have helped in developing our understanding of the molecular basis of cancer. They have also become an important component of the drug discovery and development process, and potentially of personalized medicine for the future. Bioinformatic studies are now benefiting from the wealth of large datasets generated in laboratories through the use of new high-throughput technologies and their massive public repositories of data. As of October 2015,the GEO database (www.ncbi.nih.gov/geo/) alone comprised 1,597,783 samples across 15,040 platforms, and it is being updated on a daily basis. It is becoming evident that biological data are accumulating faster than the capacity of the scientific community to analyse, integrate and mine the data, as well as to create knowledge, understanding, and insights from the data. Thus, there is a growing need for better bioinformatic tools for analyzing, mining and modelling both local and global datasets. Many data analysis projects have called for the assembly of specialized data analysis tasks and pipelines. In the future, bioinformaticians need to be involved in both methods development and in applied bioinformatics. Methods development refers to developing new algorithms, while applied bioinformatics involves putting together existing tools/pipelines in a creative way to perform an analysis task. Bioinformatics is complicated due to the heterogeneous nature of the data, varying experimental settings, small sample sizes with little replication and the existence of many distributions in the data. There is also no uniformly accepted method for large-scale integrated data analysis. The aim of this study was to develop bioinformatic and statistical tools to perform an integrated analysis of large-scale microarray gene expression, high-throughput RNAi screening and drug testing data, as well as to demonstrate the applicability of these approaches in cancer research, drug target discovery and drug testing. First,the gene tissue index (GTI) outlier analysis method was developed to identify cancer outlier genes from large-scale microarray datasets. The need to identify genes ( outlier genes ) highly expressed in a subgroup of samples rendered some of the traditional differential expression analysis methods inadequate. The GTI method enabled the analysis and mining of outlier expression profiles from heterogeneous large-scale microarray datasets that usually contain a variable number of samples for each gene being compared. Using real and simulation study datasets, the performance of the GTI method was evaluated. We observed that the GTI performed equally well in single study settings compared to existing outlier analysis methods. Furthermore, the performance of the GTI method based on discovery studies in glioblastoma and prostate cancer was notable based on the biology of the top genes identified by the GTI. This analysis revealed many genes with outlier expression patterns, and the approach is directly applicable to the identification of drug targets and cancer biomarkers, and for cancer subtype classification studies. Secondly, there have been significant concerns over the reproducibility of high-throughput screening data in the microplate format for both RNAi screening and for drug testing data in cancer cell lines. Some of this variability may be related to the study design and statistical methods, which could be further controlled. Here, we carried out a systematic study to assess the impact of normalization methods on the reproducibility and quality of high-throughput screening data with high hit rates and drug testing with dose response data. This study revealed that the hit rate and the plate layout significantly affect the performance of normalizations, and hence the quality of high-throughput screening data. Finally, high-throughput drug testing data we reanalysed for consistency across three large-scale pharmacogenomic datasets, which were systematically processed using standardized bioinformatic analysis methods while controlling assumptions for statistical inference on large-scale data matrices. We standardized data processing and analysis methods for generating dose response curves and drug response scoring across the three datasets. For example, the concentration of one drug screened at all the three sites was merged in one standard window, and the meta-analysis was performed either between cell lines or between measurements,such as genes and drugs. The results based on standardized bioinformatic analysis of drug testing and gene expression datasets demonstrated a high correlation between two of the sites tested, and moderate agreement between the others. In conclusion, broad standardization of the methods both for laboratory measurements as well as for applied bioinformatics will be necessary to ensure greater reproducibility of biological findings in cancer research and therapeutic/biomarker discovery. I envisage that improved methods for the analysis and interpretation of large-scale datasets might accelerate our ability to advance personalised medicine.
  • Kiviranta, Tuure (Helsingfors universitet, 2011)
    Työn tavoitteena on tutkia nautatilojen lannan käsittelytapojen taloudellista kannattavuutta. Tutkimuksessa verrataan lietelannan vaihtoehtoisia käsittelytapoja, joita ovat (a) lietteen levittäminen peltoon ilman esikäsittelyä, (b) lietelannan jakeistaminen typpipitoiseen nestejakeeseen ja fosforipitoiseen kuivajakeeseen sekä (c) lannan hyödyntäminen biokaasun tuotannossa. Aineistona tutkimuksessa käytetään aiempia tutkimustuloksia sekä Vieremällä sijaitsevien nautatilojen (21 kpl) tietoja. Menetelmänä käytetään lineaarista ohjelmointia ja malli ratkaistaan GAMS -ohjelmaa käyttämällä. Teoriana tutkimuksessa on tuotanto- ja kustannusteoria. Tutkimuksessa tarkastellaan kuinka eläintiheys, peltolohkorakenne sekä kustannusten muutokset vaikuttavat lannankäsittelyyn. Tutkimuksessa havaitaan, että kun kaikkea lietettä ei voida levittää tilan hallinnassa oleville pelloille, on lietteen jakeistaminen kannattavaa, jos jakeistuskustannus ei ylitä 1,2 €/m3. Sijoituslevityksen havaitaan olevan hajalevitystä kannattavampaa, paitsi typen hinnan ollessa hyvin alhainen hajalevitys on kannattavampi vaihtoehto. Korkea typpikustannus ja lietteen jakeistuskustannus tekevät biokaasun tuotannosta kannattavan vaihtoehdon, jos biokaasulaitos sijaitsee hyvin lähellä tilaa. Lietteen jakeistaminen on kannattavaa alueilla, joilla lannanlevityspinta-alasta on niukkuutta. Jakeistettavaa lietettä on kuitenkin oltava vähintään 20 000 m3/a, jotta jakeistuslaitteen hankkiminen on kannattavaa. Biokaasun tuotannon ei katsota olevan tällä hetkellä kannattava lannan käsittelyvaihtoehto, koska laitoksen olisi saatava tarvittava raaka-ainemäärä kaikissa tapauksissa alle kahden kilometrin säteeltä, eikä tämän katsota onnistuvan. Vieremän tiloista ainoastaan yksi tila sijaitsee riittävän lähellä suunniteltua laitoksen sijaintipaikkaa.
  • Kervinen, Anttoni (Helsingin yliopisto, 2015)
    Viime vuosikymmeninä tiedonalakohtaista oppimista on tutkittu paljon käsitteellisen muutoksen näkökulmasta. Käsitteellinen muutos tarkoittaa oppijan tietorakenteiden muuttumista tai jäsentymistä virheellisistä kohti tieteellistä mallia. Käsitteellisen muutoksen teorioiden mukaan oppijoiden aikaisempien virhekäsitysten tunteminen ja huomioiminen on keskeistä oppimisen ja opetuksen onnistumisen kannalta. Tässä tutkimuksessa selvitettiin biologian yliopisto-opiskelijoiden fotosynteesiin liittyviä virhekäsityksiä, niiden muuttumista opetustekstin lukemisen seurauksena sekä biologian pääaineopiskelijoiden ja sivuaineopiskelijoiden virhekäsitysten eroja. Suomalaisten opiskelijoiden virhekäsityksiä on aiemmin tutkittu niukasti. Tämän tutkimuksen tavoitteena oli selvittää virhekäsityksiä suomalaisten opetussuunnitelmien mukaan opiskelleilta opiskelijoilta sekä selvittää virhekäsitysten yksityiskohtaista muuttumista käsitteellisen muutoksen näkökulmasta. Tutkimuksen aineistona oli yliopiston biologian peruskurssin opiskelijoiden (n=171) vastaukset fotosynteesiä ja sen ekologista merkitystä koskeviin avoimiin kysymyksiin. Opiskelijat vastasivat kysymyksiin ennen opetustekstin lukemista, heti opetustekstin lukemisen jälkeen sekä kaksi viikkoa lukemisen jälkeen. Aineisto analysoitiin laadullisin menetelmin kuvaamalla, tyypittelemällä ja tulkitsemalla havaittuja virhekäsityksiä. Virhekäsitysten tulkinnassa hyödynnettiin tiedon ja ajattelutaitojen tasojen luokittelua. Opiskelijoilla havaittiin yhteensä 58 fotosynteesiä koskevaa selkeästi virheellistä käsitystä ja 14 puutteellista tai epämääräistä käsitystä. Virhekäsitykset liittyivät fotosynteesireaktioon, kasvien rakenteisiin, kasvin energiatalouteen ja fotosynteesin ekologiseen merkitykseen. Lähes kaikki virhekäsitykset ja puutteelliset käsitykset olivat yleisempiä biologian sivuaineopiskelijoilla kuin pääaineopiskelijoilla. Virhekäsitykset vähenivät opetustekstin lukemisen seurauksena, ja monimutkaisempia tiedon ja ajattelutaitojen tasoja ilmentävät virhekäsitykset vähenivät vähintään yhtä paljon kuin muutkin. Lukuisia virhekäsityksiä kuitenkin säilyi oikeat vastaukset antaneesta opetustekstistä huolimatta. Kaksi viikkoa opetustekstin lukemisen jälkeen osa jo virhekäsityksensä korjanneista opiskelijoista vastasi jälleen virheellisesti. Tutkimus osoittaa, että suomalaisen peruskoulun ja lukion fotosynteesin oppimista koskevat tavoitteet eivät täyty edes monen biologian yliopisto-opiskelijan kohdalla. Suomalaisilla opiskelijoilla on pitkälti samoja virhekäsityksiä kuin kansainvälisesti tehdyssä tutkimuksessa on havaittu. Fotosynteesin oppimisen kannalta keskeisin tutkimuksessa havaittu ymmärryksen puute on vaikeus ymmärtää fotosynteesin merkitys Auringon valoenergian ja ravintoketjujen energian välisenä linkkinä. Opiskelijoiden vaikeudet korjata virhekäsityksiään selittyvät käsitteellisen muutoksen prosessin haastavuudella ja hitaudella. Fotosynteesiä koskevan oppimisen edistämiseksi opetuksessa tulisi aiempaa paremmin huomioida käsitteellisen muutoksen haasteet kognitiivisesta, sosiaalisesta ja motivaatioon liittyvistä näkökulmista. Tämä tutkimus tarjoaa tietoa niistä fotosynteesin oppimista koskevista erityispiirteistä, joita ilmiön tehokkaaseen oppimiseen pyrkivän opetuksen tulee huomioida.
  • Zec Vojinovic, Melita (2010)
    Biological control techniques attract increasing attention as one of the sustainable alternatives to pesticide use in integrated pest management programs. In order to develop sustainable pest management methods for arable crops based on entomopathogenic nematodes (EPN), their efficacy and persistence needed to be investigated, and an economically feasible delivery system had to be developed. In this study, first a survey of entomopathogens was conducted, and a system approach was tested, using the oilseed Brassica (OSB) growing system (OSB, spring wheat, and red clover) as a model. The system approach aimed at determining the potential of Steinernema feltiae (Filipjev) for the control of OSB pests, developing OSB rotation schemes that support EPN persistence, and investigating the impact of the selected biotic and abiotic factors on efficacy and persistence of EPN. This study employed abductive logic (which employs constant interplay between the theory and empirical observation), quantitative methods, and a case study on OSB. Laboratory and field experiments were carried out, and two types of pathogen surveys. A horizontal survey included OSB fields across Estonia, Germany, Poland, Sweden and the UK, while a vertical survey included sampling from two sets of differently managed experimental fields during three years. A new approach was introduced for measuring occurrence, where the prevalence and relative intensity of entomopathogens, biotic agents, and unidentified insect antagonists were determined. The effect of dose, timing, and the application method on S. feltiae in the control of pests in OSB, and the potential of a controlled release delivery system (CRS) were evaluated in the field. Studies on the impact of selected biotic and abiotc factors (Brassica plant, bait insects, developmental stages of Meligethes aeneus Fab., Isaria fumosorosea Wize (Ifr), and organic and synthetic fertilizers) on the efficacy of S. feltiae were conducted in the laboratory. Persistence of S. feltiae in the OSB growing system, and the effect of dose, timing, and the application method, was assessed in the field as part of the efficacy experiments. The impact of selected biotic and abiotic factors on S. feltiae persistence was assessed in laboratory experiments. The pathogen survey showed that the occurrence of entomopathogens is low in the OSB growing system, and that a management system causing less disturbance (ICM) to the soil increases the relative intensity of insect parasitic nematodes and other insect antagonists. A longer study period is required to show any possible impact of ICM on the relative intensity of entomopathogenic fungi, or on the prevalence of entomopathogens. Two different measures of the occurrence yielded different results: the relative intensity revealed the difference between the two different crop management methods, while prevalence did not. The highest efficacy of S. feltiae was achieved by using a low dose and targeting all stages of M. aeneus. When only the larval stage was targeted, the application method and dose had no significant effect. The CRS decreased the pest abundance significantly more than the surface application method. S. feltiae persisted in the OSB fields in Finland for several months, but did not survive the winter. The strain survived for 7 months when it was applied in autumn in Germany, but its populations declined rapidly after winter. The examined biotic and abiotic factors had variable impacts on S. feltiae efficacy and persistence. The two measures, prevalence and relative intensity of entomopathogens, gave valuable information for their use in biocontrol programs. The recommended biocontrol strategy for OSB growing in Finland is inundation and seasonal inoculation of EPN. The impact of some biotic and abiotic factors on S. feltiae efficacy and persistence is significant, and can be used to improve the efficacy of EPN. The CRS is a novel alternative for EPN application, and should also be considered for use on other crops. Keywords: Biological control, inundation, inoculation, conservation, formulation, slow release method, crop rotation, Entomopathogenic nematodes, Steinernema feltiae, oilseed rape pests, Meligethes aeneus, Phyllotreta spp., occurrence, prevalence, intensity, efficacy, persistence, field, Isaria fumosorosea, biotic factors, abiotic factors, interaction, impact, insect stages, integrated crop management, standard (conventional) crop management