Finnish Homicides and Mental Disorders: An investigation of offense and offender characteristics

Although the majority of people with mental illness are not violent, scientific studies over the last decades show that certain psychiatric disorders increase the risk of violent behavior, including homicide. This thesis examined crime scene behaviors and offender background characteristics among mentally ill Finnish homicide offenders. Previously, homicide crime scene behaviors have been investigated in relation to offender demographic characteristics, whereas this study compares the behaviors of offenders with various mental illnesses. The study design was a retrospective chart review of the forensic psychiatric statements of Finnish homicide offenders. The work consists of four substudies. The aims of the study were as follows: To describe differences in the childhood and family backgrounds as well as in the adolescent and adult adjustment of Finnish homicide offenders belonging to different diagnostic categories (schizophrenia, personality disorder, alcoholism, drug addiction or no diagnosis). Further, the study examined associations between the crime scene behaviors and mental status of these offenders. Also, the distinguishing characteristics between two groups of offenders with schizophrenia were examined: early starters, who present antisocial behavior before the onset of schizophrenia, and late starters, who first offend after the onset of mental disorder. Finally, it was investigated how the use of excessive violence is associated with clinical and circumstantial variables as well as offender background characteristics among homicide offenders with schizophrenia. The main findings of the study can be summarized as follows. First, offenders with personality disorder or drug addiction had experienced multiple difficulties in their early environments: both family and individual problems were typical. Offenders with schizophrenia were relatively well-adjusted in childhood compared to the other groups. However, in adolescence and adulthood, social isolation, withdrawal and other difficulties attributable to these offenders illness became evident. In several aspects, offenders with alcohol dependency resembled offenders with no diagnosis in that these offenders had less problematic backgrounds compared to other groups. Second, the results showed that crime scene behaviors, victim gender and the victim-offender relationship differ between the groups. In particular, offenders with a diagnosis of schizophrenia or drug addiction have some unique features in their crime scene behaviors and choice of victims. Offenders with schizophrenia were more likely to kill a blood relative, to use a sharp weapon and to injure the victim s face. Drug addiction was associated with stealing from the victim and trying to cover up the body. Third, the results suggest that the offense characteristics of early- and late-start offenders with schizophrenia differ only modestly. However, several significant differences between the groups were found in characteristics of offenders: early starters had experienced a multitude of problems in their childhood surroundings and also later in life. Fourth, violent acts where the offender did not commit the offense alone or had previous homicidal history were predictive of excessive violence among offenders with schizophrenia. Positive psychotic symptoms did not predict the use of excessive violence. Nearly one third of the cases in the sample involved multiple and severe violence, including features such as sadism, mutilation, sexual components or extreme stabbing. In sum, mentally disordered homicide offenders are heterogeneous in their offense characteristics as well as their background characteristics. Empirically based information on how the offender s mental state is associated with specific crime scene behaviors can be utilized within the police force in developing methods of prioritizing suspects in unsolved homicide cases. Also, these results emphasise the importance of early interventions for problem families and children at risk of antisocial behavior. They may also contribute to the development of effective treatment for violent offenders.

Neural stem cell characteristics affected by oncogenic pathways and in a human motoneuron disease

Neural stem cell characteristics affected by oncogenic pathways and in a human motoneuron disease Stem cells provide the self-renewing cell pool for developing or regenerating organs. The mechanisms underlying the decisions of a stem or progenitor cell to either self-renew and maintain multipotentiality or alternatively to differentiate are incompletely understood. In this thesis work, I have approached this question by investigating the role of the proto-oncogene Myc in the regulatory functions of neural progenitor cell (NPC) self-renewal, proliferation and differentiation. By using a retroviral transduction technique to create overexpression models in embryonic NPCs cultured as neurospheres, I show that activated levels of Myc increase NPC self-renewal. Furthermore, several mechanisms that regulate the activity of Myc were identified. Myc induced self-renewal is signalled through binding to the transcription factor Miz-1 as shown by the inhibited capacity of a Myc mutant (MycV394D), deficient in binding to Miz-1, to increase self-renewal in NPCs. Furthermore, overexpression of the newly identified proto-oncogene CIP2A recapitulates the effects of Myc overexpression in NPCs. Also the expression levels and in vivo expression patterns of Myc and CIP2A were linked together. CIP2A stabilizes Myc protein levels in several cancer types by inhibiting its degradation and our results suggest the same function for CIP2A in NPCs. Our results also support the conception of self-renewal and proliferation being two separately regulated cellular functions. Finally, I suggest that Myc regulates NPC self-renewal by influencing the way stem and progenitor cells react to the environmental cues that normally dictate the cellular identity of tissues containing self-renewing cells. Neurosphere cultures were also utilised in order to characterise functional defects in a human disease. Neural stem cell cultures obtained post-mortem from foetuses of lethal congenital contracture syndrome (LCCS) were used to reveal possible cell autonomous differentiation defects of patient NPCs. However, LCCS derived NPCs were able to differentiate normally in vitro although several transcriptional differences were identified by using microarray analysis. Proliferation rate of the patient NPCs was also increased as compared to NPCs of age-matched control foetuses.

Molecular and clinical characteristics of tricarboxylic acid cycle-associated tumors

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare, dominantly inherited tumor predisposition syndrome characterized by benign cutaneous and uterine (ULM) leiomyomas, and sometimes renal cell cancer (RCC). A few cases of uterine leiomyosarcoma (ULMS) have also been reported. Mutations in a nuclear gene encoding fumarate hydratase (FH), an enzyme of the mitochondrial tricarboxylic acid cycle (TCA cycle), underlie HLRCC. As a recessive condition, germline mutations in FH predispose to a neurological defect, FH deficiency (FHD). Hereditary paragangliomatosis (HPGL) is a dominant disorder associated with paragangliomas and pheochromocytomas. Inherited mutations in three genes encoding subunits of succinate dehydrogenase (SDH), also a TCA cycle enzyme, predispose to HPGL. Both FH and SDH seem to act as tumor suppressors. One of the consequences of the TCA cycle defect is abnormal activation of HIF1 pathway ( pseudohypoxia ) in the HLRCC and HPGL tumors. HIF1 drives transcription of genes encoding e.g. angiogenetic factors which can facilitate tumor growth. Recently hypoxia/HIF1 has been suggested to be one of the causes of genetic instability as well. One of the aims of this study was to broaden the clinical definers of HLRCC. To determine the cancer risk and to identify possible novel tumor types associated with FH mutations eight Finnish HLRCC/FHD families were extensively evaluated. The extension of the pedigrees and the Finnish Cancer Registry based tumor search yielded genealogical and cancer data of altogether 868 individuals. The standardized incidence ratio-based comparison of HLRCC/FHD family members with general Finnish population revealed 6.5-fold risk for RCC. Moreover, risk for ULMS was highly increased. However, according to the recent and more stringent diagnosis criteria of ULMS many of the HLRCC uterine tumors previously considered malignant are at present diagnosed as atypical or proliferative ULMs (with a low risk of recurrence). Thus, the formation of ULMS (as presently defined) in HLRCC appears to be uncommon. Though increased incidence was not observed, interestingly the genetic analyses suggested possible association of breast and bladder cancer with loss of FH. Moreover, cancer cases were exceptionally detected in an FHD family. Another clinical finding was the conventional (clear cell) type RCC of a young Spanish HLRCC patient. Conventional RCC is distinct from the types previously observed in this syndrome but according to these results, FH mutation may underlie some of young conventional cancer cases. Secondly, the molecular pathway from defective TCA cycle to tumor formation was intended to clarify. Since HLRCC and HPGL tumors display abnormally activated HIF1, the hypothesis on the link between HIF1/hypoxia and genetic instability was of interest to study in HLRCC and HPGL tumor material. HIF1α (a subunit of HIF1) stabilization was confirmed in the majority of the specimens. However, no repression of MSH2, a protein of DNA mismatch repair system, or microsatellite instability (MSI), an indicator of genetic instability, was observed. Accordingly, increased instability seems not to play a role in the tumorigenesis of pseudohypoxic TCA cycle-deficient tumors. Additionally, to study the putative alternative functions of FH, a recently identified alternative FH transcript (FHv) was characterized. FHv was found to contain instead of exon 1, an alternative exon 1b. Differential subcellular distribution, lack of FH enzyme activity, low mRNA expression compared to FH, and induction by cellular stress suggest FHv to have a role distinct from FH, for example in apoptosis or survival. However, the physiological significance of FHv requires further elucidation.

Fuel conditions and fire behavior characteristics of managed Picea abies and Pinus sylvestris forests in Finland

The objectives of this study were to analyze the impact of structural stand characteristics on ignition potential, surface fuel moisture, and fire behavior in Pinus sylvestris L. and Picea abies (L.) Karst stands in Finland and to explain stand-specific fire danger using the Canadian Fire Weather Index System and the Finnish Fire Risk Index. Additionally, the study analyzes the relationship between observed fire activity and fire weather indices at different stages of growing season. Field experiments were carried out in Pinus sylvestris or Picea abies dominated stands during fire seasons 2001 and 2002. Observations on ignition potential, fuel moisture, and fire behavior were analyzed in relation to stand structure and the outputs of the Finnish and Canadian fire weather indices. Seasonal patterns of fire activity were examined based on national fire statistics 1996 2003, effective temperature sum, and the fire weather indices. Point fire ignition potential was highest in Pinus clear-cuts and lowest in closed Picea stands. Moss-dominated surface fuels were driest in clear-cut and sapling stage stands and presented the highest moisture content under closed Picea canopy. Pinus sylvestris stands carried fire under a wide range of fire weather conditions under which Picea abies stands failed to sustain fire. In the national fire records, the daily number of reported ignitions presented its highest value during late fire season whereas the daily area burned peaked most substantially during early season. The fire weather indices correlated significantly with ignition potential and fuel moisture but were unable to explain fire behavior in the experimental fires. During the initial and final stages of the growing season, fire activity was disconnected from weather-based fire danger ratings. Information on stand structure and season stage would benefit the assessment of fire danger in Finnish forest landscape for fire suppression and controlled burning purposes.

Chemical characteristics and behaviour of sediment phosphorus in the northeastern Baltic Sea.

Chemical characteristics and behaviour of sediment phosphorus in the northeastern Baltic Sea Eutrophication is a severe environmental problem in the Baltic Sea, especially in the Gulf of Finland and the Archipelago Sea, and it is enhanced by the release of phosphorus (P) from bottom sediments. The release of P from sediment reserves largely depends on the occurrence of P in different chemical forms and on the prevailing conditions, especially on the presence of oxygen. This study examines the chemical character and the vertical distribution of sediment P in two shallow estuaries, in shallow coastal sediments overlain by oxic near-bottom water, and in poorly oxygenated open sea sediments in the northeastern Baltic Sea. The objective was to evaluate how much of the sediment P is buried and removed from the nutrient cycle, and how much of it is in forms that can be released from the sediment to the overlaying water over time. Relationships between the distribution of the different P forms and the chemical and physical properties of the sediment, sediment pore water, and near-bottom water were determined in order to examine the behaviour of P at the sediment-water interface. The results show that the chemical character of sediment P varied in the different areas. Generally, in the outer estuaries and in the organic-rich coastal areas in the eastern Gulf of Finland, the sediments were higher in P than the sediments in the poorly oxygenated open sea areas in the central and western Gulf. The estuary sediments that received erosion-transported material were characterised by P bound to hydrated oxides of iron and aluminum. Iron-bound P is sensitive to changes in redox-conditions, but part of it was buried in the estuaries, possibly because of high sedimentation rates and incomplete reduction of iron. The open sea sediments in the central and western Gulf of Finland were dominated by apatite-P, which was also abundant in the areas strongly affected by sediment transportation. The burial of sediment P was most effective in the areas rich in apatite-P, which is a relatively stable form of P in sediment. In the eastern Gulf of Finland, organic P forms predominated in the organic-rich sediments. A part of these P forms will be buried, while part will be degraded in the long term, releasing soluble P to the pore water. In the poorly oxygenated areas, iron compounds at the sediment surface are not able to retain P released during mineralisation of organic matter or reduction-induced dissolution of iron-compounds in deep sediment layers. However, in the shallow coastal areas overlain by oxic near-bottom water, the organic-rich surface sediment can also become temporarily reduced and release P from the sediment to the overlaying water. The considerable variation in the chemical composition of sediment P reserves in the northeastern Baltic Sea proved that it is an important factor and should be taken into account when evaluating the release of sediment P and the role of P reserves in bottom sediments in eutrophication.

Syntheses and Self-Assembling Characteristics of Amphiphilic Star Diblock Copolymers

Uusien polymeeripohjaisten teknologioiden ja materiaalien myötä räätälöityjen polymeerien tarve on kasvanut. Viime vuosituhannen lopussa kehitetyt kontrolloidut polymerointimenetelmät ovat avanneet uusia mahdollisuuksia paitsi monimutkaisten polymeerien synteesiin, myös itsejärjestyvyyteen perustuvien funktionaalisten nanorakenteiden suunnitteluun ja valmistukseen. Nämä voivat jäljitellä luonnossa esiintyviä rakenteita, joita muodostavat esimerkiksi lipidit ja proteiinit. Itsejärjestyvät molekyylit ovat usein amfifiilisiä eli ne koostuvat hydrofiilisistä ja hydrofobisista osista ja polymeereissä nämä osat voivat olla omina lohkoinaan, jolloin puhutaan amfifiilisistä lohko- tai blokkikopolymeereistä. Riippuen järjestyneiden rakenteiden koostumuksesta ja muodosta, amfifiilisiä blokkikopolymeerejä on tutkittu tai jo käytetty nanoteknologiassa, elastomeereissä, voiteluaineissa, pinta-aktiivisina aineina, lääkkeenannostelussa, maaleissa, sekä elektroniikka-, kosmetiikka- ja elintarviketeollisuudessa. Tavallisimmin käytetyt amfifiiliset blokkikopolymeerit ovat olleet lineaarisia, mutta viime aikoina tutkimus on suuntautunut kohti monimutkaisempia rakenteita. Tällaisia ovat esimerkiksi tähtipolymeerit. Tähtimäisissä polymeereissä miselleille tyypillinen ydin-kuori-rakenne säilyy hyvin alhaisissakin polymeerikonsentraatioissa, koska polymeeriketjut ovat kiinni toisissaan yhdessä pisteessä. Siten ne ovat erityisen kiinnostavia tutkimuskohteita erilaisten hydrofobisten orgaanisten yhdisteiden sitomiseksi ja vapauttamiseksi. Tässä työssä on tarkasteltu amfifiilisten tähtipolymeerien itsejärjestymistä vesiliuoksissa sekä kokeellisesti ja tietokonesimulaatioin. Työ koostuu kahdesta osasta: tähtipolymeerien synteesistä makrosyklisillä initiaattoreilla ja amfifiilisten tähtimäisten blokkikopolymeerien ominaisuuksien tutkimisesta.

Structural characteristics affecting functions of two actin regulating proteins

Structural biology is a branch of science that concentrates on the relationship between the structure and function of biological macromolecules. The prevalence of a large number of three dimensional structures offers effective tools for bio-scientists to understand the living world. Actin is the most abundant cellular protein and one of its main functions is to produce movement in living cells. Actin forms filaments that are dynamic and which are regulated by a number of different proteins. A class of these regulatory proteins contains actin depolymerizing factor homology (ADF-H) domains. These directly interact with actin through their ADF-H domains. Although ADF-H domains possess very similar three dimensional structures to one another, they vary in their functional properties. One example of this is the ability to bind to actin monomers or filaments. During the work for this thesis two structures of ADF-H domains were solved by nuclear magnetic resonance spectroscopy (NMR). The elucidated structures help us understand the binding specificities of the ADF-H family members.