Human herpesvirus 6 in multiple sclerosis and encephalitis

Human herpesvirus 6 (HHV-6) was identified from patients with HIV and lymphoproliferative diseases in 1986. It is a β-herpesvirus and is divided into two subgroups, variants A and B. HHV-6 variant B is the cause of exanthema subitum, while variant A has not yet definitely proven to cause any disease. HHV-6, especially variant A, is a highly neurotropic virus and has been associated with many diseases of the central nervous system (CNS) such as encephalitis and multiple sclerosis (MS). The present studies were aimed to elucidate the role of HHV-6 and its two variants in neurological infections. Special attention was given to study the possible role of HHV-6 in the pathogenesis of MS. We studied the expression of HHV-6 antigens using immunohistochemistry in brain autopsy samples from patients with MS and controls. HHV-6 antigen was identified in 70% of MS specimens whereas 30% of control specimens expressed HHV-6 antigen. Serum and cerebrospinal fluid (CSF) samples were collected from patients with MS and patients with other neurological diseases (OND) from patients visiting Helsinki University Central Hospital Neurological Outpatient Clinic during the years 2003 and 2004. In addition, we studied 53 children with suspected encephalitis. We developed an immunofluorescence IgG-avidity assay for the detection of primary HHV-6A and HHV-6B infection. For HHV-6B antibodies, no differences were observed between patients with MS and OND. For HHV-6A both seroprevalence and mean titers were significantly higher in MS compared to OND. HHV-6A low-avidity IgG antibodies, suggestive of primary infection, were found in serum of two, three and one patient with definite MS, possible MS and OND, respectively. From pediatric patients with suspected encephalitis, six serum samples (11.3%) contained low-avidity antibodies, indicating a temporal association between HHV-6A infection and onset of encephalitis. Three out of 26 patients with CDMS and four out of 19 patients with CPMS had HHV-6 antibodies in their CSF compared to none of the patients with OND (p=0.06 and p=0.01, respectively). Two patients with CDMS and three patients with CPMS appeared to have specific intrathecal synthesis of HHV-6A antibodies. In addition, oligoclonal bands (OCB) were observed in the CSF of five out of nine MS patients tested, and in two the OCBs reacted specifically with HHV-6 antigen, which is a novel finding. These results indicate HHV-6 specific antibody production in the CNS and suggest that there is a subset of MS patients with an active or chronic HHV-6A infection in the CNS that might be involved in the pathogenesis of MS. Our studies suggest that HHV-6 is an important causative or associated virus in some neurological infections, such as encephalitis and it might contribute to the development of MS, at least in some cases. In conclusion, HHV-6 is a neurotropic virus that should be taken into consideration when studying acute and chronic CNS diseases of unknown origin.

Genetics of Cardiovascular Disease: A Candidate Gene Study of USF1

Cardiovascular diseases (CVD) are major contributors to morbidity and mortality worldwide. Several interacting environmental, biochemical, and genetic risk factors can increase disease susceptibility. While some of the genes involved in the etiology of CVD are known, many are yet to be discovered. During the last few decades, scientists have searched for these genes with genome-wide linkage and association methods, and with more targeted candidate gene studies. This thesis investigates variation within the upstream transcription factor 1 (USF1) gene locus in relation to CVD risk factors, atherosclerosis, and incidence and prevalence of CVD. This candidate gene was first identified in Finnish families ascertained for familial combined hyperlipidemia, a common dyslipidemia predisposing to coronary heart disease. The gene is a ubiquitously expressed transcription factor regulating expression of several genes from lipid and glucose metabolism, inflammation, and endothelial function. First, we examined association between USF1 variants and several CVD risk factors, such as lipid phenotypes, body composition measures, and metabolic syndrome, in two prospective population cohorts. Our data suggested that USF1 contributes to these CVD risk factors at the population level. Notably, the associations with quantitative measurements were mostly detected among study subjects with CVD or metabolic syndrome, suggesting complex interactions between USF1 effects and the pathophysiological state of an individual. Second, we investigated how variation at the USF1 locus contributes to atherosclerotic lesions of the coronary arteries and abdominal aorta. For this, we used two study samples of middle-aged men with detailed measurements of atherosclerosis obtained in autopsy. USF1 variation significantly associated with areas of several types of lesions, especially with calcification of the arteries. Next, we tested what effect the USF1 risk variants have on sudden cardiac death and incidence of CVD. The atherosclerosis-associated risk variant increased the risk of sudden cardiac death of the same study subjects. Furthermore, USF1 alleles associated with incidence of CVD in the Finnish population follow-up cohorts. These associations were especially prominent among women, suggesting a sex specific effect, which has also been detected in subsequent studies. Finally, as some of the low-yield DNA samples of the Finnish follow-up study cohort needed to be whole-genome amplified (WGA) prior to genotyping, we evaluated whether the produced WGA genotypes were of good quality. Although the samples giving genotype discrepancies could not be detected before genotyping with standard laboratory quality control methods, our results suggested that enhanced quality control at the time of the genotyping could identify such samples. In addition, combining two WGA reactions into one pooled DNA sample for genotyping markedly reduced the number of discrepancies and samples showing them. In conclusion, USF1 seems to have a role in the etiology of CVD. Additional studies are warranted to identify functional variants and to study interactions between USF1 and other genetic or environmental factors. This USF1 study, and other studies with low DNA yield of some samples, can benefit from whole genome amplification of the low-yield samples prior to genotyping. Careful quality control procedures are, however, needed in WGA genotyping.

Molecular genetics and evolution of Puumala hantavirus

Puumala virus (PUUV) is the causative agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome. Finland has the highest documented incidence of NE with around 1000 cases diagnosed annually. PUUV is also found in other Scandinavian countries, Central Europe and the European part of Russia. PUUV belongs to the genus Hantavirus in the family Bunyaviridae. Hantaviruses are rodent-borne viruses each carried by a specific host that is persistently and asymptomatically infected by the virus. PUUV is carried by the bank voles (Myodes glareolus, previously known as Clethrionomys glareolus). Hantaviruses have co-evolved with their carrier rodents for millions of years and these host animals are the evolutionary scene of hantaviruses. In this study, PUUV sequences were recovered from bank voles captured in Denmark and Russian Karelia to study the evolution of PUUV in Scandinavia. Phylogenetic analysis of these strains showed a geographical clustering of genetic variants following the presumable migration pattern of bank voles during the recolonization of Scandinavia after the last ice age approximately 10 000 years ago. The currently known PUUV genome sequences were subjected to in-depth phylogenetic analyses and the results showed that genetic drift seems to be the major mechanism of PUUV evolution. In general, PUUV seems to evolve quite slowly following a molecular clock. We also found evidence for recombination in the evolution of some genetic lineages of PUUV. Viral microevolution was studied in controlled virus transmission in colonized bank voles and changes in quasispecies dynamics were recorded as the virus was transmitted from one animal to another. We witnessed PUUV evolution in vivo, as one synonymous mutation became repeatedly fixed in the viral genome during the experiment. The detailed knowledge on the PUUV diversity was used to establish new sensitive and specific detection methods for this virus. Direct viral invasion of the hypophysis was demonstrated for the first time in a lethal case of NE. PUUV detection was done by immunohistochemistry, in situ hybridization and RT-nested-PCR of the autopsy tissue samples.

Amyloid diseases at old age : a pathological, epidemiological, and genetic study

Along with the increased life span of individuals, the burden of old age-associated diseases has inevitably increased. Alzheimer s disease (AD), probably the most well known geriatric disease, belongs to the old age-associated amyloid diseases. The purpose of this study was to investigate the frequency, genetic and health-associated risk factors, mutual association, and amyloid proteins in two old age-associated amyloid disorders senile systemic amyloidosis (SSA) and cerebral amyloid angiopathy (CAA) as part of the prospective population-based Vantaa 85+ autopsy study on a Finnish population aged 85 years or more (Studies I-III), completed with a case report on a patient with advanced AGel amyloidosis (Study IV). The numbers of patients investigated in the studies (I-III) were 256, 74, and 63, respectively. The diagnosis and grading of amyloid were based upon histological examination of tissue samples obtained post mortem and stained with Congo red. The amyloid fibril and associated proteins were characterized by immunohistochemical staining methods. The genotype frequencies of 20 polymorphisms in 9 genes and information on health-associated risk factors in subjects with and without SSA and CAA were compared. In a Finnish population ≥ 95 years of age, SSA and CAA occurred in 36% and 49% of the subjects, respectively. In total, two-thirds of these very elderly individuals had SSA, CAA, or both. However, in only 14% of the population these two conditions co-occurred. In subjects 85 years or older, the prevalence of SSA was 25%. In this population, SSA was associated with age at the time of death (p=0.002), myocardial infarctions (MIs; p=0.004), the G/G (Val/Val) genotype of the exon 24 polymorphism in the alpha2-macroglobulin (α2M) gene (p=0.042) and with the H2 haplotype of the tau gene (p=0.016). In contrast, the presence of CAA was strongly associated with APOE e4 (p=0.0003), with histopathological AD (p=0.0005), and with clinical dementia (p=0.01) in both e4+ (p=0.02) and e4- (p=0.06) individuals. Apart from demonstrating the amyloid fibril proteins, complement proteins 3d (C3d) and 9 (C9) were detected in the amyloid deposits of CAA and AGel amyloidosis, and α2M protein was found in fibrous scar tissue close to SSA. In conclusion, this first population based study on SSA shows that both SSA and CAA are common in very elderly individuals. Old age, MIs, the exon 24 polymorphism of the α2M gene, and H1/H2 polymorphism of the tau gene associate with SSA while clinical dementia and APOE ε4 genotype associate with CAA. The high prevalence of CAA, combined with its association with clinical dementia independent of APOE genotype, neuropathological AD, or SSA, also highlights its clinical significance in the very aged, among which the serious end stage complications of CAA, namely multiple infarctions and hemorrhages, are rare. The report on a patient having advanced AGel amyloidosis added knowledge on the disease and showed that this generally benign condition occasionally may lead to death. Further studies are warranted to confirm the findings in other populations. Also, the role of α2M and tau in the pathogenesis of SSA and the involvement of complement in the process of amyloid beta (Aβ) protein elimination from the brain remain to be clarified. Finally, the high prevalence of SSA in the elderly raises the need for prospective clinical studies to define its clinical significance.

The decline of northern malaria and population dynamics of Plamodium vivax

Europe was declared malaria free in 1975. The disappearance of malaria has traditionally been attributed to numerous deliberate actions like vector control, the screening of houses, more efficient medication etc. Malaria, however, disappeared from many countries like Finland before any counter measures had even started. The aim of this thesis is to study the population ecology of P. vivax and its interaction with the human host and the vector. By finding the factors that attributed to the extinction of vivax malaria it might be possible to improve the modern strategy against P. vivax. The parasite was studied with data from Finland, which provides the longest time series (1749-2008) of malaria statistics in the world. The malaria vectors, Anopheles messeae and A. beklemishevi are still common species in the country. The eradication of vivax malaria is difficult because the parasite has a dormant stage that can cause a relapse long after a primary infection. It was now shown that P. vivax is able to detect the presence of a potential vector. A dormant stage is triggered even from a bite of an uninfected Anopheles mosquito. This optimizes the chances for the Plasmodium to reach a mosquito vector for sexual reproduction. The longevity of the dormant stage could be shown to be at least nine years. The parasite spends several years in its human host and the behaviour of the human carrier had a profound impact on the decline of the disease in Finland. Malaria spring epidemics could be explained by a previous warm summer. Neither annual nor summer mean temperature had any impact on the long term malaria trend. Malaria disappeared slowly from Finland without mosquito control. The sociological change from extended families to nuclear families led to decreased household size. The decreased household size correlated strongly with the decline of malaria. That led to an increased isolation of the subpopulations of P. vivax. Their habitat consisted of the bedrooms in which human carriers slept together with the overwintering vectors. The isolation of the parasite ultimately led to the extinction of vivax malaria. Metapopulation models adapted to local conditions should therefore be implemented as a tool for settlement planning and socio-economic development and become an integrated part of the fight against malaria.

Q-evankeliumi ja psykohistoria : Uuden testamentin eksegetiikan väitöskirja

In the course of my research for my thesis The Q Gospel and Psychohistory, I moved on from the accounts of the Cynics ideals to psychohistorical explanations. Studying the texts dealing with the Cynics and the Q Gospel, I was amazed by the fact that these texts actually portrayed people living in greater poverty than they had to. I paid particular attention to the fact that the Q Gospel was born in traumatising, warlike circumstances. Psychiatric traumatology helped me understand the Q Gospel and other ancient documents using historical approaches in a way that would comply with modern behavioural science. Even though I found some answers to the questions I had posed in my research, the main result of my research work is the justification of the question: Is it important to ask whether there is a connection between the ethos expressed by means of the religious language of the Q Gospel and the predominantly war-related life experiences typical to Palestine at the time. As has been convincingly revealed by a number of studies, traumatic events contribute to the development of psychotic experiences. I approached the problematic nature, significance and complexity of the ideal of poverty and this warlike environment by clarifying the history of psychohistorical literary research and the interpretative contexts associated with Sigmund Freud, Jacques Lacan and Melanie Klein. It is justifiable to question abnormal mentality, but there is no reliable return from the abnormal mentality described in any particular text to the only affecting factor. The popular research tendency based on the Oedipus complex is just as controversial as the Oedipus complex itself. The sociological frameworks concerning moral panics and political paranoia of an outer and inner danger fit quite well with the construction of the Q Gospel. Jerrold M. Post, M.D., Professor of Psychiatry, Political Psychology and Interna-tional Affairs at George Washington University, and founder and director of the Center for the Analysis of Personality and Political Behavior for the Central Intelligence Agency, has focused on the role played by charisma in the attracting of followers and detailed the psychological styles of a "charismatic" leader. He wrote the books Political Paranoia and Leaders and Their Followers in a Dangerous World: the Psychology of Political Behavior among others. His psychoanalytic vocabulary was useful for my understanding of the minds and motivations involved in the Q Gospel s formation. The Q sect began to live in a predestined future, with the reality and safety of this world having collapsed in both their experience and their fantasies. The deep and clear-cut divisions into good and evil that are expressed in the Q Gospel reveal the powerful nature of destructive impulses, envy and overwhelming anxiety. Responsible people who influenced the Q Gospel's origination tried to mount an ascetic defense against anxiety, denying their own needs, focusing their efforts on another objective (God s Kingdom) and a regressive, submissive earlier phase of development (a child s carelessness). This spiritual process was primarily an ecclesiastic or group-dynamical tactic to give support to the power of group leaders.

The Catholic Internet discussion on cloning : A study in cognitive rhetoric

This work combines the cognitive theory of folk-theoretical thought with the classical Aristotelian theory of artistic proof in rhetoric. The first half of the work discusses the common ground shared by the elements of artistic proof (logos, pathos, ethos) and the elements of folk-theoretical thought (naïve physics, folk biology, folk psychology, naïve sociology). Combining rhetoric with the cognitive theory of folk-theoretical thought creates a new point of view for argumentation analysis. The logos of an argument can be understood as the inferential relations established between the different parts of an argument. Consequently, within this study the analysis of logos is to be viewed as the analysis of the inferential folk-theoretical elements that make the suggested factual states-of-things appear plausible within given argumentative structures. The pathos of an argumentative structure can be understood as determining the quality of the argumentation in question in the sense that emotive elements play a great part in what can be called a distinction between good and deceptive rhetoric. In the context of this study the analysis of pathos is to be viewed as the analysis of the emotive content of argumentative structures and of whether they aim at facilitating surface- or deep cognitive elaboration of the suggested matters. The ethos of an argumentative structure means both the speaker-presentation and audience-construct that can be discerned within a body of argumentation. In the context of this study, the analysis of ethos is to be understood as the analysis of mutually manifest cognitive environments in the context of argumentation. The theory is used to analyse Catholic Internet discussion concerning cloning. The discussion is divided into six themes: Human Dignity, Sacred Family, Exploitation / Dehumanisation, Playing God, Monsters and Horror Scenarios and Ensoulment. Each theme is analysed for both the rhetorical and the cognitive elements that can be seen creating persuasive force within the argumentative structures presented. It is apparent that the Catholic voices on the Internet extensively oppose cloning. The voices utilise rhetoric that is aggressive and pejorative more often than not. Furthermore, deceptive rhetoric (in the sense presented above) plays a great part in argumentative structures of the Catholic voices. The theory of folk-theoretical thought can be seen as a useful tool for analysing the possible reasons why the Catholic speakers think about cloning and choose to present cloning in their argumentation as they do. The logos utilized in the argumentative structures presented can usually be viewed as based on folk-theoretical inference concerning biology and psychology. The structures of pathos utilized generally appear to aim at generating fear appeal in the assumed audiences, often incorporating counter-intuitive elements. The ethos utilised in the arguments generally revolves around Christian mythology and issues of social responsibility. These structures can also be viewed from the point of view of folk psychology and naïve sociological assumptions.

Pyhä Teresa ja keskiajan mystiikan teoriat

In my dissertation I have studied St Teresa (1515-1582) in the light of medieval mystical theories. I have two main levels in my research: historical and theological. On the historical level I study St Teresa s personal history in the context of her family and the Spanish society. On the theological level I study both St Teresa s mysticism and her religious experience in the light of medieval mysticism. St Teresa wrote a book called Life , which is her narrative autobiography and story about her mystical spiritual formation. She reflected herself through biblical texts interpreting them in the course of the biblical hermeneutics like allegory, typology, tropology and anagogy. In addition to that she read others life stories from her period of time, but reflected herself only slightly through the sociological point of view. She used irony as a means to gain acceptance to her authority and motive to write. Her position has been described as a double bind because of writing at the request of educated men and to the non-educated women as she herself was uneducated. She used irony as a means to achieve valuation to women, to gain negative attributes connected to them and to gain authority to teach them mystical spirituality, the Bible and prayer. In this ironic tendency she was a feminist writer. In order to understand medieval mysticism I have written in the first chapter a review of the main trends in medieval mysticism in connection with the classical emotional theories. Two medieval mystical theories show an important role in St Teresa s mysticism. One is love mysticism and the other is the three partite way of mysticism (purification, illumination and union). The classic-philosophical emotional theories play a role in both patterns. The theory of love mysticism St Teresa interpreted in the traditional way stressing the spiritual meaning of love in connexion with God and neighbors. Love is an emotion, which is bound with other emotions, but all objects of love don t strengthen spiritual love. In the three partite way of mysticism purification means to find biblical values in life and to practice meditative self-knowledge theologically interpreted. In illumination human understanding has to be illuminated by God and united to mystical knowledge from God. St Teresa considered illumination a way to learn things. Illumination has also psychological aspects like recognition of many trials and pains, which come from life on earth. Theologically interpreted in illumination one should die to oneself, let oneself be transformed and renewed by God. I have also written a review of the modern philosophical discussion on personal identity where memory and mental experiences are important creators of personal identity. St Teresa bound medieval mystical teaching together with her personal religious experience. Her personal identity is by its character based on her narrative life story where mental experiences play important role. Previous researchers have labelled St Teresa as an ecstatic person whose experiences produced ecstatic phenomena to the mysticism. These phenomena combined with visions have in one respect made of her a person who has brought physical and visionary tendencies to theology. In spite of that she also represents a modern tendency trying to give words to experiences, which at first seem to be exceptional and extreme and which are easily interpreted as one-sided either physical or sexual or unsaid. In other respect I have stressed the personality of St Teresa that was represented as both strong and weak. The strong personality for her is demonstrated by religious faith and in its practice. The weak personality was for her a natural personal identity. St Teresa saw a unifying aspect in almost all. Firstly, her mysticism was aimed towards union with God and secondly, the unifying aspects and common rules in human relations in community life were central. Union with God is based on the fact that in a soul God is living in its centre, where God is present in the Trinitarian way. The picture of God in ourselves is a mirror but to get to know God better is to recognize his/her presence in us. When the soul recognizes itself as a dwelling place of God, it knows itself as God knows him/herself. There is equality between God and the soul. To be a Christian means to participate in God in his Trinitarian being. The participation to God is a process of divinization that puts a person into transformation, change and renewal. The unitive aspect concludes also knowledge of opposites between experience of community and solitude as well as community and separateness. As a founder of monasteries St Teresa practiced theology of poverty. She renewed the monastic life founding a rule called discalced that stressed ascetic tendencies. Supporters of her work were after the difficulties in the beginning both society and churchly leaders. She wrote about the monasteries including in her description at times seriousness at times humor and irony. Her stories are said to be picaresque histories that contain stories of ordinary laymen and many unexpected occasions. She exercised a kind of Bakhtinian dialogue in her letters. St Teresa stressed the virtues like sacrifice, determination and courage in the monastic life. Most of what she taught of virtues is based on biblical spirituality but there are also psychological tendencies in her writings. The theological pedagogical advice is mixed with psychology, but she herself made no distinction between different aspects in her teaching. To understand St Teresa and her mysticism is to recognize that she mixes her personal religious experience and mysticism, which widens mysticism to religious experience in a new way, although this corresponds also the very definition of mysticism. St Teresa concentrated on mental-spiritual experiences and the aim of her mystical teaching was to produce a human mind well cured like a garden that has God as its gardener.

Ihanne ja todellisuus : Jäsenyyteen sitoutuminen Suomen evankelis-luterilaisessa kirkossa 1960-luvulta 2000-luvulle

The subject of the study is the ideal and reality of commitment to membership in the Evangelical Lutheran Church of Finland from the 1960s to the 2000s. The research task is to ascertain what manner of commitment the Evangelical Lutheran Church of Finland expects from its members (the ideal) and how in reality membership of the Church is realized (empiria). The research object is also to study the extent to which the ideal of commitment evinced by the Church and the actual relation of commitment to the Church changed during the research period. Additionally, those factors were analysed which influence the relation between the ideal and reality of commitment. In the analysis of the ideal of commitment the research data are official documents of the Evangelical Lutheran Church of Finland. They include confessions of the Church, Catechisms, Christian doctrine, joint strategies and plans of the Church, likewise the Church Act and Church Order. The reality of commitment is explored on the basis of Church membership, participation in parish activity and the private practice of religion, likewise attitude to Christian faith. The empirical data of the study comprise Church statistics, material from Statistics Finland and relevant surveys implemented during the research period. The ideal of commitment alongside membership includes knowing the basic tenets of Christian faith and family life based on prayer and participation in liturgical cycles. A member of the Church is expected to take care of his/her faith by living in participation of the Word and sacrament, bearing responsibility for the parish and faithfully discharging his/her worldly obligations. There have been no major changes in the ideal of commitment during the research period. On the contrary, the reality of commitment has changed. Although the majority of Finns are still members of the Church, there has been a constant decline in their share of the population. The same can be stated with respect to parish life. This has its own strengths, among them Church rites, parish activity around feast days and also work with children and confirmation training. However, the general trend is towards a decline in participation. There has also been a decrease in commitment to belief in God as taught by the Church. On the other hand, private religious observance has not changed at all. From the perspective of commitment the Evangelical Lutheran Church of Finland exists in a state of tension between the theological ideal and sociological empiria. Matters exerting a particular influence over the relation between ideal and reality are communality and varying conceptions of the Church, likewise contextuality and the related private Christianity. Societal change poses a challenge to traditional Church communality. A decline in communality has in turn led to a decline in belonging to the Church. Weakening awareness of membership has undermined the handing down of the tradition among younger generations. Modernization has influence the identity of the Church and brought the Church to an internal divergence. This way it has been able to retain its structure as a folk church but at the same time it has lost its opportunities for the formation of a clear identity. The Church has adjusted to societal change by outward-directed activities (performance) alongside the purely religious message (function). The tension between an unchanged message and a changed operating environment has increased. The challenge of contextuality has led the Church to review parish life, the nature of teaching and activity and the language used by the Church, likewise the cultural modus. Increasingly privatized Christianity challenges above all the theology and teaching of the Church, but also the life of worship and relation to cultural life.

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

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

Mulibrey nanism : Clinical characteristics and pathophysiologic features of growth restriction, insulin resistance and tumour development

Background: Mulibrey nanism (MUL; Muscle-liver-brain-eye nanism; OMIM 253250) is an autosomal recessive growth disorder more prevalent in Finland than elsewhere in the world. Clinical characteristics include severe prenatal onset growth restriction, cardiopathy, multiple organ manifestations but no major neurological handicap. MUL is caused by mutations in the TRIM37 gene on chromosome 17q22-23, encoding a peroxisomal protein TRIM37 with ubiquitin E3-ligase activity. Nineteen different mutations have been detected, four of them present in the Finnish patients. Objective: This study aimed to characterize clinical and histopathological features of MUL in the national cohort of Finnish patients. Patients and methods: A total of 92 Finnish patients (age 0.7 to 77 years) participated in the clinical follow-up study. Patients hospital records and growth charts were reviewed. Physical, radiographic and laboratory examinations were performed according to a clinical protocol. Thirty patients (18 females) were treated with recombinant human GH for a median period of 5.7 years. Biopsies and autopsy samples were used for the histopathological and immunohistochemical analyses. Results: MUL patients were born small for gestational age (SGA) with immature craniofacial features after prenatal-onset growth restriction. They experienced a continuous deceleration in both height SDS and weight-for-height (WFH) postnatally. In infancy feeding difficulties and frequent pneumonias were common problems. At the time of diagnosis (median age 2.1 years) characteristic craniofacial, radiological and ocular features were the most constant findings. MUL patients showed a dramatic change in glucose metabolism with increasing age. While the children had low fasting glucose and insulin levels, 90% of the adults were insulin resistant, half had type 2 diabetes and an additional 42% showed impaired glucose tolerance (IGT). Seventy percent fulfilled the National Cholesterol Education Program (NCEP) Adult Treatment Panel III criteria for metabolic syndrome as adults. GH therapy improved pre-pubertal growth but had only minor impact on adult height (+5 cm). Interestingly, treated subjects were slimmer and had less frequent metabolic concerns as young adults. MUL patients displayed histologically a disturbed architecture with ectopic tissues and a high frequency of both benign and malignant tumours present in several internal organs. A total of 232 tumorous lesions were detected in our patient cohort. The majority of the tumours showed strong expression of endothelial cell marker CD34 as well as α-smooth muscle actin (α-SMA). Fifteen of the tumours were malignant and seven of them (five Wilms tumours) occurred in the kidney. Conclusions: MUL patients present a distinct postnatal growth pattern. Short-term response of GH treatment is substantial but the long-term impact remains modest. Although MUL patients form a distinct clinical and diagnostic entity, their clinical findings vary considerably from infancy to adulthood. While failure to thrive dominates early life, MUL adults develop metabolic syndrome and have a tendency for malignancies and vascular lesions in several organs. This speaks for a central role of TRIM37 in regulation of key cellular functions, such as proliferation, migration, angiogenesis and insulin signalling.

Matrix proteinases in lung injury in the preterm infant

During inflammation, excess production and release of matrix proteinases, including matrix metalloproteinases (MMPs) and serine proteinases, may result in dysregulated extracellular proteolysis leading to development of tissue damage. Pulmonary inflammation may play an important role in the pathogenesis of lung injury in the preterm infant. The aims of this study were to evaluate involvement of MMPs and serine proteinase trypsin in acute and chronic lung injury in preterm infants and to study the role of these enzymes in acute lung injury by means of an animal model of hyperoxic lung injury. Molecular forms and levels of MMP-2, -8, and -9, and their specific inhibitor, tissue inhibitor of metalloproteinases (TIMP)-2, as well as trypsin were studied in tracheal aspirate fluid (TAF) samples collected from preterm infants with respiratory distress. Expression and distribution of trypsin-2 and proteinase-activated receptor 2 (PAR2) was examined in autopsy lung specimens from fetuses, from preterm infants with respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD), and from newborn infants without lung injury. We detected higher MMP-8 and trypsin-2 and lower TIMP-2 in TAF from preterm infants with more severe acute respiratory distress. Infants subsequently developing BPD had higher levels of MMP-8 and trypsin-2 early postnatally than did those who survived without this chronic lung injury. Immunohistochemically, trypsin-2 was mainly detectable in bronchial epithelium, but also in alveolar epithelium, and its expression was strongest in prolonged RDS. Since trypsin-2 is potent activator of PAR2, a G-protein coupled receptor involved in inflammation, we studied PAR2 expression in the lung. PAR2 co-localized with trypsin-2 in bronchoalveolar epithelium and its expression was significantly higher in bronchoalveolar epithelium in preterm infants with prolonged RDS than in newborn controls. In the experimental study, rats were exposed to >95% oxygen for 24, 48, and 60 hours, or room air. At 48 hours of hyperoxia, MMP-8 and trypsin levels sharply increased in bronchoalveolar lavage fluid, and expression of trypsin appeared in alveolar epithelium, and MMP-8 predominantly in macrophages. In conclusion, high pulmonary MMP-8 and trypsin-2 early postnatally are associated with severity of acute lung injury and subsequent development of BPD in preterm infants. In the injured preterm lung, trypsin-2 co-localizes with PAR2 in bronchoalveolar epithelium, suggesting that PAR2 activated by high levels of trypsin-2 is involved in lung inflammation associated with development of BPD. Marked increase in MMP-8 and trypsin early in the course of experimental hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury. Further exploration of the roles of trypsin and MMP-8 in lung injury may offer new targets for therapeutic intervention.

The Media and the Academic Globalization Debate : Theoretical Analysis and Critique

This study offers a reconstruction and critical evaluation of globalization theory, a perspective that has been central for sociology and cultural studies in recent decades, from the viewpoint of media and communications. As the study shows, sociological and cultural globalization theorists rely heavily on arguments concerning media and communications, especially the so-called new information and communication technologies, in the construction of their frameworks. Together with deepening the understanding of globalization theory, the study gives new critical knowledge of the problematic consequences that follow from such strong investment in media and communications in contemporary theory. The book is divided into four parts. The first part presents the research problem, the approach and the theoretical contexts of the study. Followed by the introduction in Chapter 1, I identify the core elements of globalization theory in Chapter 2. At the heart of globalization theory is the claim that recent decades have witnessed massive changes in the spatio-temporal constitution of society, caused by new media and communications in particular, and that these changes necessitate the rethinking of the foundations of social theory as a whole. Chapter 3 introduces three paradigms of media research the political economy of media, cultural studies and medium theory the discussion of which will make it easier to understand the key issues and controversies that emerge in academic globalization theorists treatment of media and communications. The next two parts offer a close reading of four theorists whose works I use as entry points into academic debates on globalization. I argue that we can make sense of mainstream positions on globalization by dividing them into two paradigms: on the one hand, media-technological explanations of globalization and, on the other, cultural globalization theory. As examples of the former, I discuss the works of Manuel Castells (Chapter 4) and Scott Lash (Chapter 5). I maintain that their analyses of globalization processes are overtly media-centric and result in an unhistorical and uncritical understanding of social power in an era of capitalist globalization. A related evaluation of the second paradigm (cultural globalization theory), as exemplified by Arjun Appadurai and John Tomlinson, is presented in Chapter 6. I argue that due to their rejection of the importance of nation states and the notion of cultural imperialism for cultural analysis, and their replacement with a framework of media-generated deterritorializations and flows, these theorists underplay the importance of the neoliberalization of cultures throughout the world. The fourth part (Chapter 7) presents a central research finding of this study, namely that the media-centrism of globalization theory can be understood in the context of the emergence of neoliberalism. I find it problematic that at the same time when capitalist dynamics have been strengthened in social and cultural life, advocates of globalization theory have directed attention to media-technological changes and their sweeping socio-cultural consequences, instead of analyzing the powerful material forces that shape the society and the culture. I further argue that this shift serves not only analytical but also utopian functions, that is, the longing for a better world in times when such longing is otherwise considered impracticable.

Toiminta, valta ja kokemus organisaation muutoksessa : Tutkimus kolmesta suuryrityksestä

Action, Power and Experience in Organizational Change - A Study of Three Major Corporations This study explores change management and resistance to change as social activities and power displays through worker experiences in three major Finnish corporations. Two important sensitizing concepts were applied. Firstly, Richard Sennett's perspective on work in the new form of capitalism, and its shortcomings - the lack of commitment and freedom accompanied by the disruption to lifelong career planning and the feeling of job insecurity - offered a fruitful starting point for a critical study. Secondly, Michel Foucault's classical concept of power, treated as anecdotal, interactive and nonmeasurable, provided tools for analyzing change-enabling and resisting acts. The study bridges the gap between management and social sciences. The former have usually concentrated on leadership issues, best practices and goal attainment, while the latter have covered worker experiences, power relations and political conflicts. The study was motivated by three research questions. Firstly, why people resist or support changes in their work, work environment or organization, and the kind of analyses these behavioural choices are based on. Secondly, the kind of practical forms which support for, and resistance to change take, and how people choose the different ways of acting. Thirdly, how the people involved experience and describe their own subject position and actions in changing environments. The examination focuses on practical interpretations and action descriptions given by the members of three major Finnish business organizations. The empirical data was collected during a two-year period in the Finnish Post Corporation, the Finnish branch of Vattenfal Group, one of the leading European energy companies, and the Mehiläinen Group, the leading private medical service provider in Finland. It includes 154 non-structured thematic interviews and 309 biographies concentrating on personal experiences of change. All positions and organizational levels were represented. The analysis was conducted using the grounded theory method introduced by Straus and Corbin in three sequential phases, including open, axial and selective coding processes. As a result, there is a hierarchical structure of categories, which is summarized in the process model of change behaviour patterns. Key ingredients are past experiences and future expectations which lead to different change relations and behavioural roles. Ultimately, they contribute to strategic and tactical choices realized as both public and hidden forms of action. The same forms of action can be used in both supporting and resisting change, and there are no specific dividing lines either between employer and employee roles or between different hierarchical positions. In general, however, it is possible to conclude that strategic choices lead more often to public forms of action, whereas tactical choices result in hidden forms. The primary goal of the study was to provide knowledge which has practical applications in everyday business life, HR and change management. The results, therefore, are highly applicable to other organizations as well as to less change-dominated situations, whenever power relations and conflicting interests are present. A sociological thesis on classical business management issues can be of considerable value in revealing the crucial social processes behind behavioural patterns. Keywords: change management, organizational development, organizational resistance, resistance to change, change management, labor relations, organization, leadership

The Culture of Women's Housework : A Case Study of Bihar, India

This study examines gendered housework in India, particularly in Bihar. The perspective adopted in the study was in part derived from the data but also from sociological literature published both in Western countries and in India. The primary attention is therefore paid to modern and traditional aspects in housework. The aim is not to compare Indian practices to those of Western societies, but rather to use Western studies as a fruitful reference point. In that light, Indian housework practices appear to be traditional. Consequently, traditions are given a more significant role than is usually the case in studies on gendered housework, particularly in Western countries. The study approaches the topic mainly from the socio-cultural perspective; this provides the best means to understand the persistence of traditional habits in India. To get a wide enough picture of the division of labour, three methods were applied in the study: detailed time-use data, questionnaire and theme interviews. The data were collected in 1988 in two districts of Bihar, one rural and the other urban. The different data complement each other well but also bring to light contradictory findings: on a general level Biharian people express surprisingly modern views on gender equality but when talking in more detail (theme interviews) the interviewees told about how traditional housework practices still were in 1988. In the analysis of the data set four principal themes are discussed. Responsibility is the concept by which the study aims at understanding the logic of the argumentation on which the persistence of traditional housework practices is grounded. Contrary to the Western style, Biharian respondents appealed not to the principle of choice but to their responsibility to do what has to be done. The power of tradition, the early socialization of children to the traditional division of labour and the elusive nature of modernity are all discussed separately. In addition to the principle of responsibility, housework was also seen as an expression of affection. This was connected to housework in general but also to traditional practices. The purity principle was the third element that made Biharian interviewees favour housework in general, but as in the case of affection it too was interwoven with traditional practices. It seems to be so that if housework is in general preferred, this leads to preferring the traditional division of labour, too. The same came out when examining economic imperatives. However, the arguments concerning them proved to be rational. In analysing them it became clear that the significance of traditions is also much dependent on the economics: as far as the average income in India is very low, the prevalence of traditional practices in housework will continue. However, to make this work, cultural arguments are required: their role is to mediate more smoothly the iron rules of the economy. Key words: family, gendered housework, division of labour, responsibility, family togetherness, emotion, economy of housework, modernity, traditionality