Genetic analysis of chromosomal regions 2q33, 7q32 and 19q13 in multiple sclerosis susceptibility

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS) affecting 0.1-0.2% of Northern European descent population. MS is considered to be a multifactorial disease, both environment and genetics play a role in its pathogenesis. Despite several decades of intense research, the etiological and pathogenic mechanisms underlying MS remain still largely unknown and no curative treatment exists. The genetic architecture underlying MS is complex with multiple genes involved. The strongest and the best characterized predisposing genetic factors for MS are located, as in other immune-mediated diseases, in the major histocompatibility complex (MHC) on chromosome 6. In humans MHC is called human leukocyte antigen (HLA). Alleles of the HLA locus have been found to associate strongly with MS and remained for many years the only consistently replicable genetic associations. However, recently other genes located outside the MHC region have been proposed as strong candidates for susceptibility to MS in several studies. In this thesis a new genetic locus located on chromosome 7q32, interferon regulatory factor 5 (IRF5), was identified in the susceptibility to MS. In particular, we found that common variation of the gene was associated with the disease in three different populations, Spanish, Swedish and Finnish. We also suggested a possible functional role for one of the risk alleles with impact on the expression of the IRF5 locus. Previous studies have pointed out a possible role played by chromosome 2q33 in the susceptibility to MS and other autoimmune disorders. The work described here also investigated the involvement of this chromosomal region in MS predisposition. After the detection of genetic association with 2q33 (article-1), we extended our analysis through fine-scale single nucleotide polymorphism (SNP) mapping to define further the contribution of this genomic area to disease pathogenesis (article-4). We found a trend (p=0.04) for association to MS with an intronic SNP located in the inducible T-cell co-stimulator (ICOS) gene, an important player in the co-stimulatory pathway of the immune system. Expression analysis of ICOS revealed a novel, previously uncharacterized, alternatively spliced isoform, lacking the extracellular domain that is needed for ligand binding. The stability of the newly-identified transcript variant and its subcellular localization were analyzed. These studies indicated that the novel isoform is stable and shows different subcellular localization as compared to full-length ICOS. The novel isoform might have a regulatory function, but further studies are required to elucidate its function. Chromosome 19q13 has been previously suggested as one of the genomic areas involved in MS predisposition. In several populations, suggestive linkage signals between MS predisposition and 19q13 have been obtained. Here, we analysed the role of allelic variation in 19q13 by family based association analysis in 782 MS families collected from Finland. In this dataset, we were not able to detect any statistically significant associations, although several previously suggested markers were included to the analysis. Replication of the previous findings on the basis of linkage disequilibrium between marker allele and disease/risk allele appears notoriously difficult because of limitations such as allelic heterogeneity. Re-sequencing based approaches may be required for elucidating the role of chromosome 19q13 with MS. This thesis has resulted in the identification of a new MS susceptibility locus (IRF5) previously associated with other inflammatory or autoimmune disorders, such as SLE. IRF5 is one of the mediators of interferons biological function. In addition to providing new insight in the possible pathogenetic pathway of the disease, this finding suggests that there might be common mechanisms between different immune-mediated disorders. Furthermore the work presented here has uncovered a novel isoform of ICOS, which may play a role in regulatory mechanisms of ICOS, an important mediator of lymphocyte activation. Further work is required to uncover its functions and possible involvement of the ICOS locus in MS susceptibility.

Salmonella pathogenicity island 2 mediates protection of intracellular Salmonella from reactive nitrogen intermediates.

Salmonella typhimurium causes an invasive disease in mice that has similarities to human typhoid. A type III protein secretion system encoded by Salmonella pathogenicity island 2 (SPI2) is essential for virulence in mice, as well as survival and multiplication within macrophages. Reactive nitrogen intermediates (RNI) synthesized by inducible nitric oxide synthase (iNOS) are involved in the control of intracellular pathogens, including S. typhimurium. We studied the effect of Salmonella infection on iNOS activity in macrophages. Immunofluorescence microscopy demonstrated efficient colocalization of iNOS with bacteria deficient in SPI2 but not wild-type Salmonella, and suggests that the SPI2 system interferes with the localization of iNOS and Salmonella. Furthermore, localization of nitrotyrosine residues in the proximity was observed for SPI2 mutant strains but not wild-type Salmonella, indicating that peroxynitrite, a potent antimicrobial compound, is excluded from Salmonella-containing vacuoles by action of SPI2. Altered colocalization of iNOS with intracellular Salmonella required the function of the SPI2-encoded type III secretion system, but not of an individual "Salmonella translocated effector." Inhibition of iNOS increased intracellular proliferation of SPI2 mutant bacteria and, to a lesser extent, of wild-type Salmonella. The defect in systemic infection of a SPI2 mutant strain was partially restored in iNOS(-/-) mice. In addition to various strategies to detoxify RNI or repair damage due to RNI, avoidance of colocalization with RNI is important in adaptation of a pathogen to an intracellular life style.

Nitric Oxide Is Involved in Mycobacterium bovis Bacillus Calmette-Guerin-Activated Jagged1 and Notch1 Signaling.

Pathogenic mycobacteria have evolved unique strategies to survive within the hostile environment of macrophages. Modulation of key signaling cascades by NO, generated by the host during infection, assumes critical importance in overall cell-fate decisions. We show that NO is a critical factor in Mycobacterium bovis bacillus Calmette-Guérin-mediated Notch1 activation, as the generation of activated Notch1 or expression of Notch1 target genes matrix metalloproteinase-9 (MMP-9) or Hes1 was abrogated in macrophages derived from inducible NO synthase (iNOS) knockout (iNOS(-/-)), but not from wild-type, mice. Interestingly, expression of the Notch1 ligand Jagged1 was compromised in M. bovis bacillus Calmette-Guérin-stimulated iNOS(-/-) macrophages, and loss of Jagged1 expression or Notch1 signaling could be rescued by NO donors. Signaling perturbations or genetic approaches implicated that robust expression of MMP-9 or Hes1 required synergy and cross talk between TLR2 and canonical Notch1-PI3K cascade. Further, CSL/RBP-Jk contributed to TLR2-mediated expression of MMP-9 or Hes1. Correlative evidence shows that, in a murine model for CNS tuberculosis, this mechanism operates in vivo only in brains derived from WT but not from iNOS(-/-) mice. Importantly, we demonstrate the activation of Notch1 signaling in vivo in granulomatous lesions in the brains of Mycobacterium tuberculosis-infected human patients with tuberculous meningitis. Current investigation identifies NO as a pathological link that modulates direct cooperation of TLR2 with Notch1-PI3K signaling or Jagged1 to regulate specific components of TLR2 responses. These findings provide new insights into mechanisms by which Notch1, TLR2, and NO signals are integrated in a cross talk that modulates a defined set of effector functions in macrophages.

Fatigue fractures in military conscripts : A study on risk factors, diagnostics and long-term consequences

Fatigue fracture is an overuse injury commonly encountered in military and sports medicine, and known to relate to intensive or recently intensified physical activity. Bone responds to increased stress by enhanced remodeling. If physical stress exceeds bone s capability to remodel, accumulation of microfractures can lead to bone fatigue and stress fracture. Clinical diagnosis of stress fractures is complex and based on patient s anamnesis and radiological imaging. Bone stress fractures are mostly low-risk injuries, healing well after non-operative management, yet, occurring in high-risk areas, stress fractures can progress to displacement, often necessitating surgical treatment and resulting in prolonged morbidity. In the current study, the role of vitamin D as a predisposing factor for fatigue fractures was assessed using serum 25OHD level as the index. The average serum 25OHD concentration was significantly lower in conscripts with fatigue fracture than in controls. Evaluating TRACP-5b bone resorption marker as indicator of fatigue fractures, patients with elevated serum TRACP-5b levels had eight times higher probability of sustaining a stress fracture than controls. Among the 154 patients with exercise induced anterior lower leg pain and no previous findings on plain radiography, MRI revealed a total of 143 bone stress injuries in 86 patients. In 99% of the cases, injuries were in the tibia, 57% in the distal third of the tibial shaft. In patients with injury, forty-nine (57%) patients exhibited bilateral stress injuries. In a 20-year follow-up, the incidence of femoral neck fatigue fractures prior to the Finnish Defence Forces new regimen in 1986 addressing prevention of these fractures was 20.8/100,000, but rose to 53.2/100,000 afterwards, a significant 2.6-fold increase. In nineteen subjects with displaced femoral neck fatigue fractures, ten early local complications (in first postoperative year) were evident, and after the first postoperative year, osteonecrosis of the femoral head in six and osteoarthritis of the hip in thirteen patients were found. It seems likely that low vitamin D levels are related to fatigue fractures, and that an increasing trend exists between TRACP-5b bone resorption marker elevation and fatigue fracture incidence. Though seldom detected by plain radiography, fatigue fractures often underlie unclear lower leg stress-related pain occurring in the distal parts of the tibia. Femoral neck fatigue fractures, when displaced, lead to long-term morbidity in a high percentage of patients, whereas, when non-displaced, they do not predispose patients to subsequent adverse complications. Importantly, an educational intervention can diminish the incidence of fracture displacement by enhancing awareness and providing instructions for earlier diagnosis of fatigue fractures.

Behaviour of Bi-material interface cracks in the presence of material nonlinearity of adherends

The well known features of crack face interpenetration/contact at the tip of an interface crack is re-examined using finite element analysis and assuming material nonlinear properties for the adherends. It was assumed in literature that the crack tips are fully open at all load levels in the presence of material nonlinearity of the adherends. Analysis for the case of remote tension shows that even in the presence of material nonlinearity, crack tip closes at small load levels and opens above a certain load level. Mixed-mode fracture parameters are evaluated for the situation when the crack tips are fully open. Due to the presence of nonlinearity, the mixed-mode fracture parameters are measured with the symmetric and anti-symmetric components of J-integral. The present analysis explains the sequence of events at the interface crack tip with progressively increasing remote tension load for the case of adherends with material nonlinear behaviour.

Molecular Characterization of Fibrotic Scarring in Kidneys with Congenital Nephrotic Syndrome of the Finnish type

Congenital nephrotic syndrome of the Finnish type (NPHS1, CNF) is an autosomal recessive disease, enriched in the Finnish population. NPHS1 is caused by a mutation in the NPHS1 gene. This gene encodes for nephrin, which is a major structural component of the slit diaphragm connecting podocyte foot processes in the glomerular capillary wall. In NPHS1, the genetic defect in nephrin leads to heavy proteinuria already in the newborn period. Finnish NPHS1 patients are nephrectomized at infancy, and after a short period of dialysis the patients receive a kidney transplant, which is the only curative therapy for the disease. In this thesis, we examined the cellular and molecular mechanisms leading to the progression of glomerulosclerosis and tubulointerstitial fibrosis in NPHS1 kidneys. Progressive mesangial expansion in NPHS1 kidneys is caused by mesangial cell hyperplasia and the accumulation of extracellular matrix proteins. Expansion of the extracellular matrix was caused by the normal mesangial cell component, collagen IV. However, no significant changes in mesangial cell phenotype or extracellular matrix component composition were observed. Endotheliosis was the main ultrastructural lesion observed in the endothelium of NPHS1 glomeruli. The abundant expression of vascular endothelial growth factor and its transcription factor hypoxia inducible factor-1 alpha were in accordance with the preserved structure of the endothelium in NPHS1 kidneys. Hypoperfusion of peritubular capillaries and tubulointerstitial hypoxia were evident in NPHS1 kidneys, indicating that these may play an important role in the rapid progression of fibrosis in the kidneys of NPHS1 patients. Upregulation of Angiotensin II was obvious, emphasizing its role in the pathophysiology of NPHS1. Excessive oxidative stress was evident in NPHS1 kidneys, manifested as an increase expression of p22phox, superoxide production, lipid oxide peroxidation and reduced antioxidant activity. In conclusion, our data indicate that mesangial cell proliferation and the accumulation of extracellular matrix accumulation are associated with the obliteration of glomerular capillaries, causing the reduction of circulation in peritubular capillaries. The injury and rarefaction of peritubular capillaries result in impairment of oxygen and nutrient delivery to the tubuli and interstitial cells, which correlates with the fibrosis, tubular atrophy and oxidative stress observed in NPHS1 kidneys.

Design of mechanism-based inhibitors of transthyretin amyloidosis:Studies with biphenyl ethers and new structural templates

Transthyretin (TTR), a tetrameric thyroxine (T4) carrier protein, is associated with a variety of amyloid diseases. In this study, we explore the potential of biphenyl ethers (BPE), which are shown to interact with a high affinity to its T4 binding site thereby preventing its aggregation and fibrillogenesis. They prevent fibrillogenesis by stabilizing the tetrameric ground state of transthyretin. Additionally, we identify two new structural templates (2-(5-mercapto-[1,3,4]oxadiazol-2-yl)-phenol and 2,3,6-trichloro-N-(4H-[1,2,4]triazol-3-yl) represented as compounds 11 and 12, respectively, throughout the manuscript) exhibiting the ability to arrest TTR amyloidosis. The dissociation constants for the binding of BPEs and compound 11 and 12 to TTR correlate with their efficacies of inhibiting amyloidosis. They also have the ability to inhibit the elongation of intermediate fibrils as well as show nearly complete (> 90%) disruption of the preformed fibrils. The present study thus establishes biphenyl ethers and compounds 11 and 12 as very potent inhibitors of TTR fibrillization and inducible cytotoxicity.

Identification of protein interaction regions of VINC/NEAT1/Men epsilon RNA

The virus inducible non-coding RNA (VINC) was detected initially in the brain of mice infected with Japanese encephalitis virus (JEV) and rabies virus. VINC is also known as NEAT1 or Men epsilon RNA. It is localized in the nuclear paraspeckles of several murine as well as human cell lines and is essential for paraspeckle formation. We demonstrate that VINC interacts with the paraspeckle protein, P54nrb through three different protein interaction regions (PIRs) one of which (PIR-1) is localized near the 50 end while the other two (PIR-2, PIR-3) are localized near the 30 region of VINC. Our studies suggest that VINC may interact with P54nrb through a novel mechanism which is different from that reported for protein coding RNAs. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

Cultural Trauma and Life Stories

The purpose of this work is to use the concepts of human time and cultural trauma in a biographical study of the turning points in the recent history of Estonia. This research is primarily based on 148 in-depth biographical interviews conducted in Estonia and Sweden in 1995-2005, supplemented by excerpts from 5 collections and 10 individually published autobiographies. The main body of the thesis consists of six published and of two forthcoming separate refereed articles, summarised in the theoretical introduction, and Appendix of the full texts of three particular life stories. The topic of the first article is the generational composition and the collective action frames of anti-Soviet social mobilisation in Estonia in 1940-1990. The second article details the differentiation of the rites of passage and the calendar traditions as a strategy to adapt to the rapidly changed political realities, comparatively in Soviet Estonia and among the boat-refugees in Sweden. The third article investigates the life stories of the double-minded strategic generation of the Estonian-inclined Communists, who attempted to work within the Soviet system while professing to uphold the ideals of pre-war Estonia. The fourth article is concentrated on the problems of double mental standards as a coping strategy in a contradictory social reality. The fifth article implements the theory of cultural trauma for the social practice of singing nationalism in Estonia. The sixth article bridges the ideas of Russian theoreticians concerning cultural dialogue and the Western paradigm of cultural trauma, with examples from Estonian Russian life stories. The seventh article takes a biographical look at the logic of the unraveling of cultural trauma through four Soviet decades. The eighth article explores the re-shaping of citizen activities as a strategy of coping with the loss of the independent nation state, comparatively in Soviet Estonia and among Swedish Estonians. Cultural trauma is interpreted as the re-ordering of the society s value-normative constellation due to sharp, violent, usually political events. The first one under consideration was caused by the occupations of the Republic of Estonia by the Soviet army in 1940-45. After half a century of suppression the memories of these events resurfaced as different stories describing the long-term, often inter-generational strategies of coping with the value collapse. The second cultural trauma is revealed together with the collapse of the Soviet power and ideology in Estonia in 1991. According to empirical data, the following three trauma discourses have been reconstructed: - the forced adaptation to Soviet order of the homeland Estonians; - the difficulty of preserving Estonian identity in exile (Sweden); - the identity crisis of the Russian population of Estonia. Comparative analyses of these discourses have shown that opposing experiences and worldviews cause conflicting interpretations of the past. Different social and ethnic groups consider coping with cultural trauma as a matter of self-defence and create appropriate usable pasts to identify with. Keywords: human time, cultural trauma, frame analysis, discourse, life stories

Design of mechanism-based inhibitors of transthyretin amyloidosis: Studies with biphenyl ethers and new structural templates

Transthyretin (TTR), a tetrameric thyroxine (T4) carrier protein, is associated with a variety of amyloid diseases. In this study, we explore the potential of biphenyl ethers (BPE), which are shown to interact with a high affinity to its T4 binding site thereby preventing its aggregation and fibrillogenesis. They prevent fibrillogenesis by stabilizing the tetrameric ground state of transthyretin. Additionally, we identify two new structural templates (2-(5-mercapto-[1,3,4]oxadiazol-2-yl)-phenol and 2,3,6-trichloro-N-(4H-[1,2,4]triazol-3-yl) represented as compounds 11 and 12, respectively, throughout the manuscript) exhibiting the ability to arrest TTR amyloidosis. The dissociation constants for the binding of BPEs and compound 11 and 12 to TTR correlate with their efficacies of inhibiting amyloidosis. They also have the ability to inhibit the elongation of intermediate fibrils as well as show nearly complete (> 90%) disruption of the preformed fibrils. The present study thus establishes biphenyl ethers and compounds 11 and 12 as very potent inhibitors of TTR fibrillization and inducible cytotoxicity.

Puolustuskykyinen valtio vai Ruotsin hälytyskello? : Suomen sotilasstrateginen asema kylmän sodan alkuvuosien asiantuntija-arvioissa

The doctoral thesis deals with Finnish and foreign expert s analyses of Finland s military strategic position and defence capability, dating back to the early years of the Cold War. Finland s military high command prepared assessments of the country s strategic position and of the capability of the Defence Forces as grounds for defence planning. Since Finland was located on the Cold War dividing line, the foreign powers were also monitoring the development of Finland s situation. The research carried out had access to the armed forces internal assessments, as well as to analyses prepared by the military intelligence services of Sweden, Britain and the United States. One of the working hypotheses was that after the WWII the ability military leadership to estimate the security political needs of the country and the organisation of its defence was severely weakened so that the dangers of the international development were not perceived and the gradual erosion of defence capability was partly unnoticed. This hypothesis proved to be wrong. Even if the Finnish military intelligence was much weaker than during the war, it was able to provide the military leadership with information of the international military development for the most part. The military leadership was also fully aware of the weakening of the defence capability of the country. They faced the difficult task of making the country s political leadership, i.e. President Paasikivi and the government, also understand the gravity of the situation. Only in the last years of his term in office Paasikivi started to believe the warnings of the military. According to another hypothesis, outside observers considered the Finnish armed forces to primarily act as reinforcements for the Soviet Red Army, and they believed that, in the event of a full-scale war, the Finns would not have been able or even willing to resist a Soviet invasion of Sweden and Norway through Finland. The study confirmed that this was approximately the view the Swedes, the British and the Americans had of the Finnish forces. Western and Swedish intelligence assessments did not show confidence in Finland s defence ability and the country was regarded almost as a Soviet satellite. Finland s strategic position was, however, considered slightly different from that of the Soviet-occupied Eastern European countries. Finland had been forced to become part of the Soviet sphere of interest and security system and this was sealed by the Finno-Soviet Treaty of Friendship, Cooperation, and Mutual Assistance in 1948. Finland had little importance to the military interests of the Western powers. In Sweden s defence planning, however, Finland played a significant role as an alarm bell of a possible Soviet surprise attack, as well as defensive frontline and buffer zone.

Heme oxygenase-1 in cardiovascular diseases

Myocardial infarction (MI) and heart failure are major causes of morbidity and mortality worldwide. Treatment of MI involves early restoration of blood flow to limit infarct size and preserve cardiac function. MI leads to left ventricular remodeling, which may eventually progress to heart failure, despite the established pharmacological treatment of the disease. To improve outcome of MI, new strategies for protecting the myocardium against ischemic injury and enhancing the recovery and repair of the infarcted heart are needed. Heme oxygenase-1 (HO-1) is a stress-responsive and cytoprotective enzyme catalyzing the degradation of heme into the biologically active reaction products biliverdin/bilirubin, carbon monoxide (CO) and free iron. HO-1 plays a key role in maintaining cellular homeostasis by its antiapoptotic, anti-inflammatory, antioxidative and proangiogenic properties. The present study aimed, first, at evaluating the role of HO-1 as a cardioprotective and prohealing enzyme in experimental rat models and at investigating the potential mechanisms mediating the beneficial effects of HO-1 in the heart. The second aim was to evaluate the role of HO-1 in 231 critically ill intensive care unit (ICU) patients by investigating the association of HO-1 polymorphisms and HO-1 plasma concentrations with illness severity, organ dysfunction and mortality throughout the study population and in the subgroup of cardiac patients. We observed in an experimental rat MI model, that HO-1 expression was induced in the infarcted rat hearts, especially in the infarct and infarct border areas. In addition, pre-emptive HO-1 induction and CO donor pretreatment promoted recovery and repair of the infarcted hearts by differential mechanisms. CO promoted vasculogenesis and formation of new cardiomyocytes by activating c-kit+ stem/progenitor cells via hypoxia-inducible factor 1 alpha, stromal cell-derived factor 1 alpha (SDF-1a) and vascular endothelial growth factor B, whereas HO-1 promoted angiogenesis possibly via SDF-1a. Furthermore, HO-1 protected the heart in the early phase of infarct healing by increasing survival and proliferation of cardiomyocytes. The antiapoptotic effect of HO-1 persisted in the late phases of infarct healing. HO-1 also modulated the production of extracellular matrix components and reduced perivascular fibrosis. Some of these beneficial effects of HO-1 were mediated by CO, e.g. the antiapoptotic effect. However, CO may also have adverse effects on the heart, since it increased the expression of extracellular matrix components. In isolated perfused rat hearts, HO-1 induction improved the recovery of postischemic cardiac function and abrogated reperfusion-induced ventricular fibrillation, possibly in part via connexin 43. We found that HO-1 plasma levels were increased in all critically ill patients, including cardiac patients, and were associated with the degree of organ dysfunction and disease severity. HO-1 plasma concentrations were also higher in ICU and hospital nonsurvivors than in survivors, and the maximum HO-1 concentration was an independent predictor of hospital mortality. Patients with the HO-1 -413T/GT(L)/+99C haplotype had lower HO-1 plasma concentrations and lower incidence of multiple organ dysfunction. However, HO-1 polymorphisms were not associated with ICU or hospital mortality. The present study shows that HO-1 is induced in response to stress in both experimental animal models and severely ill patients. HO-1 played an important role in the recovery and repair of infarcted rat hearts. HO-1 induction and CO donor pretreatment enhanced cardiac regeneration after MI, and HO-1 may protect against pathological left ventricular remodeling. Furthermore, HO-1 induction potentially may protect against I/R injury and cardiac dysfunction in isolated rat hearts. In critically ill ICU patients, HO-1 plasma levels correlate with the degree of organ dysfunction, disease severity, and mortality, suggesting that HO-1 may be useful as a marker of disease severity and in the assessment of outcome of critically ill patients.

Characteristics of yeasts isolated from phenol- and catechol-adapted activated sludges

Phenol- and catechol-adapted sludges contained large numbers of the yeasts, Candida tropicalis and Trichosporon cutaneum. Both were able to grow on a variety of aromatic compounds and utilized phenol and catechol at a high rate. This property was inducible. The feasibility of using these yeasts for removing phenols from waste waters is suggested.

Paimen vailla hiippakuntaa : Kenttäpiispan viran synty ja vaikutus sotilaspapiston asemaan Suomen puolustusvoimissa ja kirkossa vuosina 1939 - 1944

The main purpose of this research is to shed light on the factors that gave rise to the office of Field Bishop in the years 1939-1944. How did military bishophood affect the status of the head of military pastoral care and military clergy during these years? The main sources of my research are the collections in the Finnish National Archives, and I use a historical-qualitative method. The position of the military clergy was debated within both the Church and the Defence Forces before 1939. At that stage, Church law did not yet recognize the office of the leading military priest, the Field Dean. There had been a motion in 1932 to introduce the office of a military bishop, but the bishops' synod blocked it. The concept of Field Bishop appeared for the first time in 1927 in a Finnish military document, which dealt with pastoral care in the Polish military. The Field Dean in Finland had regularly proposed improvements to the salary of the military clergy before the Winter War. After the Winter War, arguments were made for strengthening the position of the military clergy: these arguments were based on the increased respect shown towards this clergy, especially due to their role in the care of the fallen, which had become their task during the war. Younger members of the military clergy in particular supported the demands to improve their position within the Church and the army. The creation of a Field Bishop was perceived as strengthening the whole military clergy, as the Field Bishop was envisioned as a bishop within the Church and a general within the Defence Forces. During that time the Field Dean was still without any military rank. The idea of a Field Bishop was recommended to Mannerheim in June 1940, after which the Defence Forces lent their support to the cause. The status of the military clergy, in Church law, made it to the agenda of the Church council in January 1941, thanks largely to the younger priests' group influence and Mannerheim's leverage. The bishops opposed the notion of a Field Bishop mostly on theological grounds but were ready to concede that the position the Field Dean in Church law required further defining. The creation of the office of Field Bishop was blocked in the Church law committee report issued close to the beginning of the Continuation War. The onset of that war, however, changed the course of events, as the President of the Republic appointed Field Dean Johannes Björklund as Field Bishop. Speculation has abounded about Mannerheim's role in the appointment, but the truth of the matter is not clear. The title of Field Bishop was used to put pressure on the Church, and, at the same time, Mannerheim could remain detached from the matter. Later, in September 1941, the Church council approved the use of the Field Bishop title to denote the head of military pastoral care in Church law, and Field Bishops were assigned some of the duties formerly pertaining to bishops. Despite all expectations and hopes, the new office of Field Bishop did not affect the status of the military clergy within the Defence Forces, as no ranks were established for them, and their salary did not improve. However the office of the Field Bishop within Army HQ was transformed from a bureau into a department in the summer of 1942. At the beginning of the Continuation War, the Field Bishop was criticized by certain military and Church clergy for favouring Russian Orthodox Christians in Eastern Karelia. Björklund agreed in principle with most of the Lutheran clergy on the necessity of Lutheranizing East Karelia but had to take into account the realities at Army HQ. As well, at the same time the majority of the younger clergy were serving in the army, and there was a lack of parish priests on the home front. Bishop Lehtonen had actually expressed the wish that more priests could have been released from the front to serve in local parishes. In his notes Lehtonen accused Björklund of trying to achieve the position of Field Bishop by all possible means. However, research has revealed a varied group of people behind the creation of the office of Field Bishop, including in particular younger clergy and the Defence Forces.

The Art of Adaptation : A study on the Europeanization of Finland's foreign and security policy

This study examines how Finnish foreign and security policy has been influenced by the European Union and its Common Foreign and Security Policy. It points to a growing interplay and misfit between the external expectations originating from the European level and the domestic expectations and traditional ways-of-doing-things. It is concluded that the deepening European integration in the sphere of foreign, security and defence policy has played a significant role in a number of transformations in the Finnish policies since 1995. New, more European, meanings have been attached to the key concepts of Finnish foreign and security policy. Neutrality and traditional peacekeeping have been replaced by a minimalist reading of military non-alignment and participation in crisis management operations and EU battle groups. Traditional small state identity has been recast more and more as small member stateness . At the same time Finland has entered an era of post-consensus in national foreign and security policy. A key theoretical argument in the background of the study is that collective understandings attached to European policies, when not resonating well with domestic understandings, cause adaptation pressures on domestic-level processes and may lead to changes in the way interests and identities are constructed. This means that Europeanization is principally seen as identity reconstruction. Consequently, the theoretical framework of the study builds on the Europeanization research literature and constructivist IR theory on state identity. Foreign and security policy is defined as the practice in which state identity is reproduced, and the key foreign and security policy concepts are seen as the vehicles of identity production. It is concluded that for Finland, participation in the EU s foreign, security and defence policies represents not only a tool for responding to the changes in the international security environment but also a new means of self-identification. Concerning the Finnish attempts of projecting national interests on the European security policy agenda, it is concluded that they mainly relate to the compatibility of the potential development of EU s defence dimension with the Finnish military non-alignment. Although neutrality was cast aside in the official security policy when Finland joined the EU, the analysis shows that its impact has continued in the domestic political debate and in the mind-set of the decision-makers. The primary research material includes official Finnish foreign and security policy documentation and the related parliamentary debates from 1994 to 2007. This study serves also as a comprehensive empirical overview on Finland s reactions and contributions to the EU Common Foreign and Security Policy.