Genetic Variation and Clinical Manifestations in Inflammatory Bowel Disease

Crohn s disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD), are characterised by chronic inflammation of the gastrointestinal tract. IBD prevalence in Finland is approximately 3-4 per 1000 inhabitants with a peak incidence in adolescence. The symptoms of IBD include diarrhoea, abdominal pain, fever, and weight loss. The precise aetiology of IBD is unknown but interplay of environmental risk factors and immunologic changes trigger the disease in a genetically susceptible individual. Twin and family studies have provided strong evidence for genetic factors in IBD susceptibility, and genetic factors may be more prominent in CD than UC. The first CD susceptibility gene was identified in 2001. Three common mutations R702W, G908R, and 1007fs of the CARD15/NOD2 gene are shown to associate independently with CD but the magnitude of association varies between different populations. The present study aimed at identifying mutations and genetic variations in IBD susceptibility and candidate genes. In addition, correlation to phenotype was also assessed. One of the main objectives of this study was to evaluate the role of CARD15 in a Finnish CD cohort. 271 CD patients were studied for the three common mutations and the results showed a lower mutation frequency than in other Caucasian populations. Only 16% of the patients carried one of the three mutations. Ileal location as well as stricturing and penetrating behaviour of the disease were associated with occurrence of the mutations. The whole protein coding region of CARD15 was screened for possible Finnish founder mutations. In addition to several sequence variants, five novel mutations (R38M, W355X, P727L, W907R, and R1019X) were identified in five patients. Functional consequences of these novel variants were studied in vitro, and these studies demonstrated a profound impairment of MDP response. Investigation of CARD15 mutation frequency in healthy people across three continents showed a large geographic fluctuation. No simple correlation between mutation frequency and disease incidence was seen in populations studied. The occurrence of double mutant carriers in healthy controls suggested that the penetrance of risk alleles is low. Other main objectives aimed at identifying other genetic variations that are involved in the susceptibility to IBD. We investigated the most plausible IBD candidate genes including TRAF6, SLC22A4, SLC22A5, DLG5, TLR4, TNFRSF1A, ABCB1/MDR1, IL23R, and ATG16L1. The marker for a chromosome 5 risk haplotype and the rare HLA-DRB1*0103 allele were also studied. The study cohort consisted of 699 IBD patients (240 CD and 459 UC), of which 23% had a first-degree relative with IBD. Of the several candidate genes studied, IL23R was associated with CD susceptibility, and TNFRSF1A as well as the HLA-DRB1*0103 allele with UC susceptibility. IL23R variants also showed association with the stricturing phenotype and longer disease duration in CD patients. In addition, TNFRSF1A variants were more common among familial UC and ileocolonic CD. In conclusion, the common CARD15 mutations were shown to account for 16% of CD cases in Finland. Novel CARD15 variants identified in the present study are most likely disease-causing mutations, as judged by the results of in vitro studies. The present study also confirms the IL23R association with CD susceptibility and, in addition, TNFRSF1A and HLA-DRB1*0103 allele association with UC of specific clinical phenotypes.

Regulating Food Consumption : Studies of change and variation in Europe

The role of people as buyers and eaters of food has changed significantly. From being protected by a paternalistic welfare state, people appear to be accorded more freedom and responsibility as individuals, where attention is redirected from the state towards market relations. Many have asserted that these changes are accompanied by fragmentation, individualisation, and privatisation, leading to individual uncertainty and lack of confidence. But empirical observations do not always confirm this, distrust is not necessarily growing and while responsibilities may change, the state still plays an active role. This dissertation explores changing relationships between states and markets, on the one hand, and ordinary people in their capacities as consumers and citizens, on the other. Do we see the emergence of new forms of regulation of food consumption? If so, what is the scope and what are the characteristics? Theories of regulation addressing questions about individualisation and self-governance are combined with a conceptualisation of consumption as processes of institutionalisation, involving daily routines, the division of labour between production and consumption, and the institutional field in which consumption is embedded. The analyses focus on the involvement of the state, food producers and scientific, first of all nutritional, expertise in regulating consumption, and on popular responses. Two periods come out as important, first when the ideas of “designing the good life” emerged, giving the state a very particular role in regulating food consumption, and, second, when this “designing” is replaced by ideas of choice and individual responsibility. One might say that “consumer choice” has become a mode of regulation. I use mainly historical studies from Norway to analyse the shifting role of the state in regulating food consumption, complemented with population surveys from six European countries to study how modernisation processes are associated with trust. The studies find that changing regulation is not only a question of societal or state vs individual responsibilities. Degrees of organisation and formalisation are important as well. While increasing organisation may represent discipline and abuses of power (including exploitation of consumer loyalty), organisation can also, to the consumer, provide higher predictability, systems to deal with malfeasance, and efficiency which may provide conditions for acting. The welfare state and the neo-liberal state have very different types of solutions. The welfare state solution is based on (national) egalitarianism, paternalism and discipline (of the market as well as households). Such solutions are still prominent in Norway. Individualisation and self-regulation may represent a regulatory response not only to a declining legitimacy of this kind of interventionism, but also increasing organisational complexity. This is reflected in large-scale re-regulation of markets as well as in relationships with households and consumers. Individualisation of responsibility is to the consumer not a matter of the number of choices that are presented on the shelves, but how choice as a form of consumer based involvement is institutionalised. It is recognition of people as “end-consumers”, as social actors, with systems of empowerment politically as well as via the provisioning system. ‘Consumer choice’ as a regulatory strategy includes not only communicative efforts to make people into “choosing consumers”, but also the provision of institutions which recognise consumer interests and agency. When this is lacking we find distrust as representing powerlessness. Individual responsibility-taking represents agency and is not always a matter of loyal support to shared goals, but involves protest and creativity. More informal (‘communitarian’) innovations may be an indication of that, where self-realisation is intimately combined with responsibility for social problems. But as solutions to counteract existing imbalances of power in the food market the impacts of such initiatives are probably more as part of consumer mobilisation and politicisation than as alternative provisioning.

Genetic variation in the LDL receptor-related protein 5 (LRP5) gene : Association with bone health and metabolic parameters

Bone mass accrual and maintenance are regulated by a complex interplay between genetic and environmental factors. Recent studies have revealed an important role for the low-density lipoprotein receptor-related protein 5 (LRP5) in this process. The aim of this thesis study was to identify novel variants in the LRP5 gene and to further elucidate the association of LRP5 and its variants with various bone health related clinical characteristics. The results of our studies show that loss-of-function mutations in LRP5 cause severe osteoporosis not only in homozygous subjects but also in the carriers of these mutations, who have significantly reduced bone mineral density (BMD) and increased susceptibility to fractures. In addition, we demonstrated for the first time that a common polymorphic LRP5 variant (p.A1330V) was associated with reduced peak bone mass, an important determinant of BMD and osteoporosis in later life. The results from these two studies are concordant with results seen in other studies on LRP5 mutations and in association studies linking genetic variation in LRP5 with BMD and osteoporosis. Several rare LRP5 variants were identified in children with recurrent fractures. Sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses revealed no disease-causing mutations or whole-exon deletions. Our findings from clinical assessments and family-based genotype-phenotype studies suggested that the rare LRP5 variants identified are not the definite cause of fractures in these children. Clinical assessments of our study subjects with LPR5 mutations revealed an unexpectedly high prevalence of impaired glucose tolerance and dyslipidaemia. Moreover, in subsequent studies we discovered that common polymorphic LRP5 variants are associated with unfavorable metabolic characteristics. Changes in lipid profile were already apparent in pre-pubertal children. These results, together with the findings from other studies, suggest an important role for LRP5 also in glucose and lipid metabolism. Our results underscore the important role of LRP5 not only in bone mass accrual and maintenance of skeletal health but also in glucose and lipid metabolism. The role of LRP5 in bone metabolism has long been studied, but further studies with larger study cohorts are still needed to evaluate the specific role of LRP5 variants as metabolic risk factors.

Essays on Risk Modeling. Applications to Portfolio and Risk Management (summary section only)

In this thesis we deal with the concept of risk. The objective is to bring together and conclude on some normative information regarding quantitative portfolio management and risk assessment. The first essay concentrates on return dependency. We propose an algorithm for classifying markets into rising and falling. Given the algorithm, we derive a statistic: the Trend Switch Probability, for detection of long-term return dependency in the first moment. The empirical results suggest that the Trend Switch Probability is robust over various volatility specifications. The serial dependency in bear and bull markets behaves however differently. It is strongly positive in rising market whereas in bear markets it is closer to a random walk. Realized volatility, a technique for estimating volatility from high frequency data, is investigated in essays two and three. In the second essay we find, when measuring realized variance on a set of German stocks, that the second moment dependency structure is highly unstable and changes randomly. Results also suggest that volatility is non-stationary from time to time. In the third essay we examine the impact from market microstructure on the error between estimated realized volatility and the volatility of the underlying process. With simulation-based techniques we show that autocorrelation in returns leads to biased variance estimates and that lower sampling frequency and non-constant volatility increases the error variation between the estimated variance and the variance of the underlying process. From these essays we can conclude that volatility is not easily estimated, even from high frequency data. It is neither very well behaved in terms of stability nor dependency over time. Based on these observations, we would recommend the use of simple, transparent methods that are likely to be more robust over differing volatility regimes than models with a complex parameter universe. In analyzing long-term return dependency in the first moment we find that the Trend Switch Probability is a robust estimator. This is an interesting area for further research, with important implications for active asset allocation.

Test of the Clustering Hypothesis in the Helsinki Exchanges

This paper investigates the clustering pattern in the Finnish stock market. Using trading volume and time as factors capturing the clustering pattern in the market, the Keim and Madhavan (1996) and the Engle and Russell (1998) model provide the framework for the analysis. The descriptive and the parametric analysis provide evidences that an important determinant of the famous U-shape pattern in the market is the rate of information arrivals as measured by large trading volumes and durations at the market open and close. Precisely, 1) the larger the trading volume, the greater the impact on prices both in the short and the long run, thus prices will differ across quantities. 2) Large trading volume is a non-linear function of price changes in the long run. 3) Arrival times are positively autocorrelated, indicating a clustering pattern and 4) Information arrivals as approximated by durations are negatively related to trading flow.

Real-Time PCR : A Molecular Approach to Investigate the Role of Intestinal Microbiota in the Pathophysiology of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common multifactorial functional intestinal disorder, the pathogenesis of which is not completely understood. Increasing scientific evidence suggests that microbes are involved in the onset and maintenance of IBS symptoms. The microbiota of the human gastrointestinal (GI) tract constitutes a massive and complex ecosystem consisting mainly of obligate anaerobic microorganisms making the use of culture-based methods demanding and prone to misinterpretation. To overcome these drawbacks, an extensive panel of species- and group-specific assays for an accurate quantification of bacteria from fecal samples with real-time PCR was developed, optimized, and validated. As a result, the target bacteria were detectable at a minimum concentration range of approximately 10 000 bacterial genomes per gram of fecal sample, which corresponds to the sensitivity to detect 0.000001% subpopulations of the total fecal microbiota. The real-time PCR panel covering both commensal and pathogenic microorganisms was assessed to compare the intestinal microbiota of patients suffering from IBS with a healthy control group devoid of GI symptoms. Both the IBS and control groups showed considerable individual variation in gut microbiota composition. Sorting of the IBS patients according to the symptom subtypes (diarrhea, constipation, and alternating predominant type) revealed that lower amounts of Lactobacillus spp. were present in the samples of diarrhea predominant IBS patients, whereas constipation predominant IBS patients carried increased amounts of Veillonella spp. In the screening of intestinal pathogens, 17% of IBS samples tested positive for Staphylococcus aureus, whereas no positive cases were discovered among healthy controls. Furthermore, the methodology was applied to monitor the effects of a multispecies probiotic supplementation on GI microbiota of IBS sufferers. In the placebo-controlled double-blind probiotic intervention trial of IBS patients, each supplemented probiotic strain was detected in fecal samples. Intestinal microbiota remained stable during the trial, except for Bifidobacterium spp., which increased in the placebo group and decreased in the probiotic group. The combination of assays developed and applied in this thesis has an overall coverage of 300-400 known bacterial species, along with the number of yet unknown phylotypes. Hence, it provides good means for studying the intestinal microbiota, irrespective of the intestinal condition and health status. In particular, it allows screening and identification of microbes putatively associated with IBS. The alterations in the gut microbiota discovered here support the hypothesis that microbes are likely to contribute to the pathophysiology of IBS. The central question is whether the microbiota changes described represent the cause for, rather than the effect of, disturbed gut physiology. Therefore, more studies are needed to determine the role and importance of individual microbial species or groups in IBS. In addition, it is essential that the microbial alterations observed in this study will be confirmed using a larger set of IBS samples of different subtypes, preferably from various geographical locations.

Variation i kvinnors namnfraser i officiella dokument i Helsingfors 1780-1930 : Socioonomastiska synvinklar på makt och identitet

This dissertation is an onomastic study of variation in women s name phrases in official documents in Finland during the period 1780−1930. The aim is to discuss from a socio-onomastic perspective both the changeover from patronymics to inherited family names and the use of surnames after marriage (i.e. whether women adopted their husbands family names or retained their maiden names), before new laws in this area entered into force in Finland in the early 20th century. In 1920, a law on family names that required fixed names put an end to the use of the patronymic as a person s only surname. After 1929, it was no longer possible for a married woman to retain her maiden name. Methodologically, to explain this development from a socio-onomastic perspective, I have based my study on a syntactic-semantic analysis of the actual name phrases. To be able to demonstrate the extensive material, I have elaborated a scheme to divide the 115 different types of name phrases into 13 main categories. The analysis of the material for Helsinki is based on frequency calculations of the different types of name phrases every thirtieth year, as well as on describing variation in the structure and semantic content of the name phrases, e.g. social variation in the use of titles and epithets. In addition to this, by applying a biographic-genealogical method, I have conducted two case studies of the usage of women s name phrases in the two chosen families. The study is based on parish registers from the period 1780−1929, estate inventory documents from the period 1780−1928, registration forms for liberty of trade from the period 1880−1908, family announcements on newspapers from the period 1829−1888, gravestones from the period 1796−1929 and diaries from the periods 1799−1801 and 1818−1820 providing a corpus of 5 950 name phrases. The syntactic-semantic analysis has revealed the overall picture of various ways of denoting women in official documents. In Helsinki, towards the end of the 19th century, the use of inherited family names seems to be almost fully developed in official contexts. At the late 19th century, a patronymic still appears as the only surname of some working-class women whereas in the early 20th century patronymics were only entered in the parish register as a kind of middle name. In the beginning of the 19th century, most married women were still registered under their maiden names, with a few exceptions among the bourgeoisie and upper class. The comparative analysis of name phrases in diaries, however, indicates that the use of the husband s family name by married women was a much earlier phenomenon in private contexts than in official documents. Keywords: socio-onomastics, syntactic-semantic analysis, name phrase, patronymic, maiden name, husband s family name

Associations of interleukin-1 (IL-1) gene variation and IL-1 receptor antagonist phenotypes with immunological responses, metabolic dysregulation and type 2 diabetes

The upstream proinflammatory interleukin-1 (IL-1) cytokines, together with a naturally occurring IL-1 receptor antagonist (IL-1Ra), play a significant role in several diseases and physiologic conditions. The IL-1 proteins affect glucose homeostasis at multiple levels contributing to vascular injuries and metabolic dysregulations that precede diabetes. An association between IL-1 gene variations and IL-1Ra levels has been suggested, and genetic studies have reported associations with metabolic dysregulation and altered inflammatory responses. The principal aims of this study were to: 1) examine the associations of IL-1 gene variation and IL-1Ra expression in the development and persistence of thyroid antibodies in subacute thyroiditis; 2) investigate the associations of common variants in the IL-1 gene family with plasma glucose and insulin concentrations, glucose homeostasis measures and prevalent diabetes in a representative population sample; 3) investigate genetic and non-genetic determinants of IL-1Ra phenotypes in a cross-sectional setting in three independent study populations; 4) investigate in a prospective setting (a) whether variants of the IL-1 gene family are predictors for clinically incident diabetes in two population-based observational cohort studies; and (b) whether the IL-1Ra levels predict the progression of metabolic syndrome to overt diabetes during the median follow-up of 10.8 and 7.1 years. Results from on patients with subacte thyroiditis showed that the systemic IL-1Ra levels are elevated during a specific proinflammatory response and they correlated with C-reactive protein (CRP) levels. Genetic variation in the IL-1 family seemed to have an association with the appearance of thyroid peroxidase antibodies and persisting local autoimmune responses during the follow-up. Analysis of patients suffering from diabetes and metabolic traits suggested that genetic IL-1 variation and IL-1Ra play a role in glucose homeostasis and in the development of type 2 diabetes. The coding IL-1 beta SNP rs1143634 was associated with traits related to insulin resistance in cross-sectional analyses. Two haplotype variants of the IL-1 beta gene were associated with prevalent diabetes or incident diabetes in a prospective setting and both of these haplotypes were tagged by rs1143634. Three variants of the IL-1Ra gene and one of the IL-1 beta gene were consistently identified as significant, independent determinants of the IL-1Ra phenotype in two or three populations. The proportion of the phenotypic variation explained by the genetic factors was modest however, while obesity and other metabolic traits explained a larger part. Body mass index was the strongest predictor of systemic IL-1Ra concentration overall. Furthermore, the age-adjusted IL-1Ra concentrations were elevated in individuals with metabolic syndrome or diabetes when compared to those free of metabolic dysregulation. In prospective analyses the systemic IL-1Ra levels were found as independent predictors for the development of diabetes in people with metabolic syndrome even after adjustment for multiple other factors, including plasma glucose and CRP levels. The predictive power of IL-1Ra was better than that of CRP. The prospective results also provided some evidence for a role of common IL-1 alpha promoter SNP rs1800587 in the development of type 2 diabetes among men and suggested that the role may be gender specific. Likewise, common variations in the IL-1 beta coding region may have a gender specific association with diabetes development. Further research on the potential benefits of IL-1Ra measurements in identifying individuals at high risk for diabetes, who then could be targeted for specific treatment interventions, is warranted. It has been reported in the recent literature that IL-1Ra secreted from adipose tissue has beneficial effects on glucose homeostasis. Furthermore, treatment with recombinant human IL-1Ra has been shown to have a substantial therapeutic potential. The genetic results from the prospective analyses performed in this study remain inconclusive, but together with the cross-sectional analyses they suggest gender-specific effects of the IL-1 variants on the risk of diabetes. Larger studies with more extensive genotyping and resequencing may help to pinpoint the exact variants responsible and to further elucidate the biological mechanisms for the observed associations. This would improve our understanding of the pathways linking inflammation and obesity with glucose and insulin metabolism.

Talouskäsitysten vaikutus hallituksen suosioon Puolassa 2006–2007

Tutkimuksessa tarkastellaan äänestäjien talouskäsitysten vaikutusta hallituksen suosioon Puolassa vuosina 2006 ja 2007. Tutkimusasetelma juontaa juurensa poliittisten suhdannevaihteluiden teoriaan, jonka mukaan poliitikot pyrkivät manipuloimaan taloutta vaalien alla tullakseen uudelleen valituiksi. Vastuullisuushypoteesin mukaan äänestäjät palkitsevat poliitikot hyvästä taloustilanteesta. Näin ollen mikäli äänestäjät ovat tyytyväisiä talouteen he äänestävät hallitusta. Mikäli eivät, he äänestävät oppositiota. Miten äänestäjät sitten tekevät arvionsa taloudesta? Tutkielmassa selvitetään vaikuttiko äänestäjien mielipiteisiin käsitys nykyisestä vai tulevaisuuden taloustilanteesta. Käsitys nykyisestä taloustilanteesta perustuu havaintoihin jo toteutuneesta talouspolitiikasta. Tätä käsitystä kutsutaan retrospektiiviseksi näkemykseksi. Prospektiiviset talousnäkemykset koostuvat näkemyksestä ja odotuksista talouden tulevasta tilasta ja uskosta hallituksen kykyyn tarjota paras vaihtoehto suotuisalle talouskehitykselle. Aikaulottuvuuden lisäksi tutkielmassa testataan, vaikuttaako äänestäjiin enemmän heidän oma taloustilanteensa vai näkemys yleisestä talouden tilanteesta. Mikäli hallituksen suosio perustuu näkemyksiin henkilökohtaisen talouden tilasta, ovat äänestäjät egotrooppisia. Mikäli kannatuspäätös perustuu näkemykseen kansantalouden tilasta, ovat äänestäjät puolestaan sosiotrooppisia. Aineistona tutkielmassa käytetään uusinta saatavilla olevaa Puolan mielipidetiedustelun (Centrum Badania Opinii Publicznej) keräämää kyselyaineistoa vuosilta 2006 ja 2007. Tutkielmassa on yhdistetty kyselyaineistot 22:n kuukauden ajalta. Aineistoa on analysoitu logistisen regressioanalyysin menetelmin. Tutkielman perusteella talousnäkemyksistä suurin vaikutus hallituksen suosioon on äänestäjien näkemyksillä kansantalouden tulevaisuuden tilasta. Henkilökohtaisen talouden osalta positiiviset tulevaisuudennäkymät vaikuttavat positiivisesti myös hallituksen kannatukseen. Retrospektiivinen arvio henkilökohtaisesta taloudesta toimii kuitenkin teorian vastaisesti; oman taloudellisen tilanteen hyväksi arvioineiden todennäköisyys kannatta hallitusta oli pienempää kuin niillä, jotka arvioivat oman taloustilanteensa huonoksi. Kontrollimuuttujiksi valittiin joukko aiemmassa tutkimuksessa äänestyskäyttäytymiseen Puolassa vaikuttaneita tekijöitä. Näitä olivat ikä, sukupuoli, koulutus, asuinpaikka, näkemys työllisyystilanteesta, ideologinen sijoittuminen oikeisto–vasemmisto-akselilla sekä uskonnollisuus. Kontrollimuuttujista merkitseviksi osoittautuivat uskonnollisuus, oikeisto–vasemmisto-ideologia, koulutus, asuinpaikka sekä ikä. Kun edellä mainitut taustamuuttujat on kontrolloitu, taloustekijät selittävät noin viidesosan hallituksen kannatuksen todennäköisyyden vaihtelusta.

Using a botanic garden collection to test a bioclimatic vegetation scheme

Vegetation maps and bioclimatic zone classifications communicate the vegetation of an area and are used to explain how the environment regulates the occurrence of plants on large scales. Many practises and methods for dividing the world’s vegetation into smaller entities have been presented. Climatic parameters, floristic characteristics, or edaphic features have been relied upon as decisive factors, and plant species have been used as indicators for vegetation types or zones. Systems depicting vegetation patterns that mainly reflect climatic variation are termed ‘bioclimatic’ vegetation maps. Based on these it has been judged logical to deduce that plants moved between corresponding bioclimatic areas should thrive in the target location, whereas plants moved from a different zone should languish. This principle is routinely applied in forestry and horticulture but actual tests of the validity of bioclimatic maps in this sense seem scanty. In this study I tested the Finnish bioclimatic vegetation zone system (BZS). Relying on the plant collection of Helsinki University Botanic Garden’s Kumpula collection, which according to the BZS is situated at the northern limit of the hemiboreal zone, I aimed to test how the plants’ survival depends on their provenance. My expectation was that plants from the hemiboreal or southern boreal zones should do best in Kumpula, whereas plants from more southern and more northern zones should show progressively lower survival probabilities. I estimated probability of survival using collection database information of plant accessions of known wild origin grown in Kumpula since the mid 1990s, and logistic regression models. The total number of accessions I included in the analyses was 494. Because of problems with some accessions I chose to separately analyse a subset of the complete data, which included 379 accessions. I also analysed different growth forms separately in order to identify differences in probability of survival due to different life strategies. In most analyses accessions of temperate and hemiarctic origin showed lower survival probability than those originating from any of the boreal subzones, which among them exhibited rather evenly high probabilities. Exceptionally mild and wet winters during the study period may have killed off hemiarctic plants. Some winters may have been too harsh for temperate accessions. Trees behaved differently: they showed an almost steadily increasing survival probability from temperate to northern boreal origins. Various factors that could not be controlled for may have affected the results, some of which were difficult to interpret. This was the case in particular with herbs, for which the reliability of the analysis suffered because of difficulties in managing their curatorial data. In all, the results gave some support to the BZS, and especially its hierarchical zonation. However, I question the validity of the formulation of the hypothesis I tested since it may not be entirely justified by the BZS, which was designed for intercontinental comparison of vegetation zones, but not specifically for transcontinental provenance trials. I conclude that botanic gardens should pay due attention to information management and curational practices to ensure the widest possible applicability of their plant collections.

Association between molecular variation in the phosphoglucose isomerase (Pgi) locus and migration propensity in the Glanville fritillary butterfly

Habitat fragmentation produces patches of suitable habitat surrounded by unfavourable matrix habitat. A species may persist in such a fragmented landscape in an equilibrium between the extinctions and recolonizations of local populations, thus forming a metapopulation. Migration between local populations is necessary for the long-term persistence of a metapopulation. The Glanville fritillary butterfly (Melitaea cinxia) forms a metapopulation in the Åland islands in Finland. There is migration between the populations, the extent of which is affected by several environmental factors and variation in the phenotype of individual butterflies. Different allelic forms of the glycolytic enzyme phosphoglucose isomerase (Pgi) has been identified as a possible genetic factor influencing flight performance and migration rate in this species. The frequency of a certain Pgi allele, Pgi-f, follows the same pattern in relation to population age and connectivity as migration propensity. Furthermore, variation in flight metabolic performance, which is likely to affect migration propensity, has been linked to genetic variation in Pgi or a closely linked locus. The aim of this study was to investigate the association between Pgi genotype and the migration propensity in the Glanville fritillary both at the individual and population levels using a statistical modelling approach. A mark-release-recapture (MRR) study was conducted in a habitat patch network of M. cinxia in Åland to collect data on the movements of individual butterflies. Larval samples from the study area were also collected for population level examinations. Each butterfly and larva was genotyped at the Pgi locus. The MRR data was parameterised with two mathematical models of migration: the Virtual Migration Model (VM) and the spatially explicit diffusion model. VM model predicted and observed numbers of emigrants from populations with high and low frequencies of Pgi-f were compared. Posterior predictive data sets were simulated based on the parameters of the diffusion model. Lack-of-fit of observed values to the model predicted values of several descriptors of movements were detected, and the effect of Pgi genotype on the deviations was assessed by randomizations including the genotype information. This study revealed a possible difference in the effect of Pgi genotype on migration propensity between the two sexes in the Glanville fritillary. The females with and males without the Pgi-f allele moved more between habitat patches, which is probably related to differences in the function of flight in the two sexes. Females may use their high flight capacity to migrate between habitat patches to find suitable oviposition sites, whereas males may use it to acquire mates by keeping a territory and fighting off other intruding males, possibly causing them to emigrate. The results were consistent across different movement descriptors and at the individual and population levels. The effect of Pgi is likely to be dependent on the structure of the landscape and the prevailing environmental conditions.

Patterns in permuted binary matrices

Reorganizing a dataset so that its hidden structure can be observed is useful in any data analysis task. For example, detecting a regularity in a dataset helps us to interpret the data, compress the data, and explain the processes behind the data. We study datasets that come in the form of binary matrices (tables with 0s and 1s). Our goal is to develop automatic methods that bring out certain patterns by permuting the rows and columns. We concentrate on the following patterns in binary matrices: consecutive-ones (C1P), simultaneous consecutive-ones (SC1P), nestedness, k-nestedness, and bandedness. These patterns reflect specific types of interplay and variation between the rows and columns, such as continuity and hierarchies. Furthermore, their combinatorial properties are interlinked, which helps us to develop the theory of binary matrices and efficient algorithms. Indeed, we can detect all these patterns in a binary matrix efficiently, that is, in polynomial time in the size of the matrix. Since real-world datasets often contain noise and errors, we rarely witness perfect patterns. Therefore we also need to assess how far an input matrix is from a pattern: we count the number of flips (from 0s to 1s or vice versa) needed to bring out the perfect pattern in the matrix. Unfortunately, for most patterns it is an NP-complete problem to find the minimum distance to a matrix that has the perfect pattern, which means that the existence of a polynomial-time algorithm is unlikely. To find patterns in datasets with noise, we need methods that are noise-tolerant and work in practical time with large datasets. The theory of binary matrices gives rise to robust heuristics that have good performance with synthetic data and discover easily interpretable structures in real-world datasets: dialectical variation in the spoken Finnish language, division of European locations by the hierarchies found in mammal occurrences, and co-occuring groups in network data. In addition to determining the distance from a dataset to a pattern, we need to determine whether the pattern is significant or a mere occurrence of a random chance. To this end, we use significance testing: we deem a dataset significant if it appears exceptional when compared to datasets generated from a certain null hypothesis. After detecting a significant pattern in a dataset, it is up to domain experts to interpret the results in the terms of the application.