Characterisation of properties of coniferous wood tracheids by x-ray diffraction, laser scattering and microscopy

In recent years there has been growing interest in selecting suitable wood raw material to increase end product quality and to increase the efficiency of industrial processes. Genetic background and growing conditions are known to affect properties of growing trees, but only a few parameters reflecting wood quality, such as volume and density can be measured on an industrial scale. Therefore research on cellular level structures of trees grown in different conditions is needed to increase understanding of the growth process of trees leading to desired wood properties. In this work the cellular and cell wall structures of wood were studied. Parameters, such as the mean microfibril angle (MFA), the spiral grain angles, the fibre length, the tracheid cell wall thickness and the cross-sectional shape of the tracheid, were determined as a function of distance from the pith towards the bark and mutual dependencies of these parameters were discussed. Samples from fast-grown trees, which belong to a same clone, grown in fertile soil and also from fertilised trees were measured. It was found that in fast-grown trees the mean MFA decreased more gradually from the pith to the bark than in reference stems. In fast-grown samples cells were shorter, more thin-walled and their cross-sections were rounder than in slower-grown reference trees. Increased growth rate was found to cause an increase in spiral grain variation both within and between annual rings. Furthermore, methods for determination of the mean MFA using x-ray diffraction were evaluated. Several experimental arrangements including the synchrotron radiation based microdiffraction were compared. For evaluation of the data analysis procedures a general form for diffraction conditions in terms of angles describing the fibre orientation and the shape of the cell was derived. The effects of these parameters on the obtained microfibril angles were discussed. The use of symmetrical transmission geometry and tangentially cut samples gave the most reliable MFA values.

Lung structure and function studied by synchrotron radiation

A novel method for functional lung imaging was introduced by adapting the K-edge subtraction method (KES) to in vivo studies of small animals. In this method two synchrotron radiation energies, which bracket the K-edge of the contrast agent, are used for simultaneous recording of absorption-contrast images. Stable xenon gas is used as the contrast agent, and imaging is performed in projection or computed tomography (CT) mode. Subtraction of the two images yields the distribution of xenon, while removing practically all features due to other structures, and the xenon density can be calculated quantitatively. Because the images are recorded simultaneously, there are no movement artifacts in the subtraction image. Time resolution for a series of CT images is one image/s, which allows functional studies. Voxel size is 0.1mm3, which is an order better than in traditional lung imaging methods. KES imaging technique was used in studies of ventilation distribution and the effects of histamine-induced airway narrowing in healthy, mechanically ventilated, and anaesthetized rabbits. First, the effect of tidal volume on ventilation was studied, and the results show that an increase in tidal volume without an increase in minute ventilation results a proportional increase in regional ventilation. Second, spiral CT was used to quantify the airspace volumes in lungs in normal conditions and after histamine aerosol inhalation, and the results showed large patchy filling defects in peripheral lungs following histamine provocation. Third, the kinetics of proximal and distal airway response to histamine aerosol were examined, and the findings show that the distal airways react immediately to histamine and start to recover, while the reaction and the recovery in proximal airways is slower. Fourth, the fractal dimensions of lungs was studied, and it was found that the fractal dimension is higher at the apical part of the lungs compared to the basal part, indicating structural differences between apical and basal lung level. These results provide new insights to lung function and the effects of drug challenge studies. Nowadays the technique is available at synchrotron radiation facilities, but the compact synchrotron radiation sources are being developed, and in relatively near future the method may be used at hospitals.

Näkökulmia eurooppalaiseen sosiaalipolitiikkaan : malli, väestö, resurssit ja kommunikaatio

The study analyses European social policy as a political project that proceeds under the guidance of the European Commission. In the name of modernisation, the project aims to build a new idea for the welfare state. To understand the project, it is necessary to distance oneself from both the juridical competence of the European Union and the traditional national welfare state models. The question is about sharing problems, as well as solutions to them: it is the creation and sharing of common views, concepts and images that play a key role in European integration. Drawing on texts and speeches produced by the European Commission, the study throws light on the development of European social policy during the first years of the 2000s. The study "freeze-frames" the welfare debate having its starting points in the nation states in the name of the entity of Europe. The first article approaches the European social model as a story in itself, a preparatory, persuasive narrative that concerns the management of change. The article shows how the audience can be motivated to work towards a set target by using discursive elements in a persuasive manner: the function of a persuasive story is to convince the target audience of the appropriateness of the chosen direction and to shape their identity so that they are favourably disposed to the desired political targets. This is a kind of "intermediate state" where the story, despite its inner contradictions and inaccuracies, succeeds in appearing as an almost self-evident path towards a modern social policy that Europe is currently seen to be in need of. The second article outlines the European social model as a question of governance. Health as a sector of social policy is detached from the old political order, which was based on the welfare state, and is closely linked to economy. At the same time the population is primarily seen as an economic resource. The Commission is working towards a "Europe of Health" that grapples with the problem of governance with the help of the "healthisation" of society, healthy citizenship and health economics. The way the Commission speaks is guided by the Union's powerful interest to act as "Europe" in the field of welfare policy. At the same time, the traditional separateness of health policy is effaced in order to be able to make health policy reforms a part of the Union's wider modernisation targets. The third article then shows the European social policy as its own area of governance. The article uses an approach based on critical discourse analysis in examining the classification systems and presentation styles adopted by Commission communications, as well as the identities that they help build. In analysing the "new start" of the Lisbon strategy from the perspective of social policy, the article shows how the emphasis has shifted from the persuasive arguments for change with necessary common European targets in the early stages of the strategy towards the implementation of reforms: from a narrative to a vision and from a diagnosis to healing. The phase of global competition represents "the modern" with which European society with its culture and ways of life now has to be matched. The Lisbon strategy is a way to direct this societal change, thus building a modern European social policy. The fourth article describes how the Commission uses its communications policy to build practices and techniques of governance and how it persuades citizens to participate in the creation of a European project of change. This also requires a new kind of agency: agents for whom accountability and responsibilities mean integration into and commitment to European society. Accountability is shaped into a decisive factor in implementing the European Union's strategy of change. As such it will displace hierarchical confrontations and emphasise common action with a view to modernising Europe. However, the Union's discourse cannot be described as being a political language that would genuinely rouse and convince the audience at the level of everyday life. Keywords: European social policy, EU policy, European social model, European Commission, modernisation of welfare, welfare state, communications, discoursiveness.

Transcription factor GATA4 and apoptotic TRAIL pathway in granulosa cell function and tumors

Normal growth and development require the precise control of gene expression. Transcription factors are proteins that regulate gene expression by binding specific sequences of DNA. Abnormalities in transcription are implicated in a variety of human diseases, including cancer, endocrine disorders and birth defects. Transcription factor GATA4 has emerged as an important regulator of normal development and function in a variety of endoderm- and mesoderm- derived tissues, including gut, heart and several endocrine organs, such as gonads. Mice harboring a null mutation of Gata4 gene die during embryogenesis due to failure in heart formation, complicating the study of functional role of GATA4 in other organs. However, the expression pattern of GATA4 suggests it may play a role in the regulation of ovarian granulosa cell development, function and apoptosis. This premise is supported by in vitro studies showing that GATA4 regulates several steroidogenic enzymes as well as auto-, para- and endocrine signaling molecules important for granulosa cell function. This study assessed the in vivo role of GATA4 for granulosa cell function by utilizing two genetically modified mouse strains. The findings in the GATA4 deficient mice included delayed puberty, impaired fertility and signs of diminished estrogen production. At the molecular level, the GATA4 deficiency leads to attenuated expression of central steroidogenic genes, Steroidogenic acute regulatory protein (StAR), Side-chain cleavage (SCC), and aromatase as a response to stimulations with exogenous gonadotropins. Taken together, these suggest GATA4 is necessary for the normal ovarian function and female fertility. Programmed cell death, apoptosis, is a crucial part of normal ovarian development and function. In addition, disturbances in apoptosis have been implicated to pathogenesis of human granulosa cell tumors (GCTs). Apoptosis is controlled by extrinsic and intrinsic pathways. The intrinsic pathway is regulated by members of Bcl-2 family, and its founding member, the anti-apoptotic Bcl-2, is known to be important for granulosa cell survival. This study showed that the expression levels of GATA4 and Bcl-2 correlate in the human GCTs and that GATA4 regulates Bcl-2 expression, presumably by directly binding to its promoter. In addition, disturbing GATA4 function was sufficient to induce apoptosis in cultured GCT- derived cell line. Taken together, these results suggest GATA4 functions as an anti-apoptotic factor in GCTs. The extrinsic apoptotic pathway is controlled by the members of tumor necrosis factor (TNF) superfamily. An interesting ligand of this family is TNF-related apoptosis-inducing ligand (TRAIL), possessing a unique ability to selectively induce apoptosis in malignant cells. This study characterized the previously unknown expression of TRAIL and its receptors in both developing and adult human ovary, as well as in malignant granulosa cell tumors. TRAIL pathway was shown to be active in GCTs suggesting it may be a useful tool in treating these malignancies. However, more studies are required to assess the function of TRAIL pathway in normal ovaries. In addition to its ability to induce apoptosis in GCTs, this study revealed that GATA4 protects these malignancies from TRAIL-induced apoptosis. GATA4 presumably exerts this effect by regulating the expression of anti-apoptotic Bcl-2. This is of particular interest as high expression of GATA4 is known to correlate to aggressive GCT behavior. Thus, GATA4 seems to protect GCTs from endogenous TRAIL by upregulating anti-apoptotic factors such as Bcl-2.

Cystatin C, a measure of renal function, as prognostic risk marker in acute heart failure : Studies on the cardiorenal syndrome

Acute heart failure (AHF) is a complex syndrome associated with exceptionally high mortality. Still, characteristics and prognostic factors of contemporary AHF patients have been inadequately studied. Kidney function has emerged as a very powerful prognostic risk factor in cardiovascular disease. This is believed to be the consequence of an interaction between the heart and kidneys, also termed the cardiorenal syndrome, the mechanisms of which are not fully understood. Renal insufficiency is common in heart failure and of particular interest for predicting outcome in AHF. Cystatin C (CysC) is a marker of glomerular filtration rate with properties making it a prospective alternative to the currently used measure creatinine for assessment of renal function. The aim of this thesis is to characterize a representative cohort of patients hospitalized for AHF and to identify risk factors for poor outcome in AHF. In particular, the role of CysC as a marker of renal function is evaluated, including examination of the value of CysC as a predictor of mortality in AHF. The FINN-AKVA (Finnish Acute Heart Failure) study is a national prospective multicenter study conducted to investigate the clinical presentation, aetiology and treatment of, as well as concomitant diseases and outcome in, AHF. Patients hospitalized for AHF were enrolled in the FINN-AKVA study, and mortality was followed for 12 months. The mean age of patients with AHF is 75 years and they frequently have both cardiovascular and non-cardiovascular co-morbidities. The mortality after hospitalization for AHF is high, rising to 27% by 12 months. The present study shows that renal dysfunction is very common in AHF. CysC detects impaired renal function in forty percent of patients. Renal function, measured by CysC, is one of the strongest predictors of mortality independently of other prognostic risk markers, such as age, gender, co-morbidities and systolic blood pressure on admission. Moreover, in patients with normal creatinine values, elevated CysC is associated with a marked increase in mortality. Acute kidney injury, defined as an increase in CysC within 48 hours of hospital admission, occurs in a significant proportion of patients and is associated with increased short- and mid-term mortality. The results suggest that CysC can be used for risk stratification in AHF. Markers of inflammation are elevated both in heart failure and in chronic kidney disease, and inflammation is one of the mechanisms thought to mediate heart-kidney interactions in the cardiorenal syndrome. Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) correlate very differently to markers of cardiac stress and renal function. In particular, TNF-α showed a robust correlation to CysC, but was not associated with levels of NT-proBNP, a marker of hemodynamic cardiac stress. Compared to CysC, the inflammatory markers were not strongly related to mortality in AHF. In conclusion, patients with AHF are elderly with multiple co-morbidities, and renal dysfunction is very common. CysC demonstrates good diagnostic properties both in identifying impaired renal function and acute kidney injury in patients with AHF. CysC, as a measure of renal function, is also a powerful prognostic marker in AHF. CysC shows promise as a marker for assessment of kidney function and risk stratification in patients hospitalized for AHF.

Kuoleman voimat : Kirkonväki suomalaisessa uskomusperinteessä

Powers of Death. Church-väki in the Finnish Folk Belief Tradition Folk belief tradition can be defined as a communication system in which the truth value of traditional motifs is judged by their usefulness and applicability. According to the Finnish belief tradition, a substance of power called väki resides in sacred elements and in entities which vitally affect human life. Väki is both ritually avoided and harnessed for beneficial or malevolent purposes. The powers of church and death merge in church-väki, which, in beliefs and narratives, emerges when the boundary between the living and the dead is crossed or violated. In rural societies where the relationship to the dying and the deceased was close, the church-väki tradition was relevant and productive. This study is based on approximately 2700 units of archived material from thel late 19th and early 20th centuries narratives, rite descriptions, and linguistic data. It explicates the concept of church-väki, presents the background of the tradition, and analyses narratives, their meanings, and their role in early modern world view. It also explores how the concept was used when constructing social boundaries and handling otherness in the early modern Finland. The theoretic emphasis is on conceptual and genre analysis, narrativity, as well as the multiple meanings and uses of folklore motifs. Descriptions of church-väki vary from it being an invisible force to a crowd of beings and decomposing corpses. The author defines church-väki as a fuzzy concept with three prototypical cores and several names, most of which are polysemous. Polysemous words connect church-väki with for example ghosts and devils, unkempt people, and vermin, constructing a loose paradigm of supernatural and social otherness. Folklore genres of the studied narratives range from stories of personal experience to fabulates. The taleworlds and their content range from realistic (near) to extraordinary (distant). The distance between the taleworld and reality has concrete (local and temporal), narrative, and normative aspects. Distant taleworlds often follow an ontology different than in real life, although the narratives may be carefully linked to reality. Instead of being fictive, they show what would be expected outside the socially constructed everyday order. Methods of narratology are applied to coherent legends, which locate dramatic events in distant taleworlds. Linguistic genres, based on structure, function here as narrative registers of folklore genres.

Role and function of nonmuscle alpha-actinin-1 and -4 in regulating distinct subcategories of actin stress fibers in mammalian cells

Actin stress fibers are dynamic structures in the cytoskeleton, which respond to mechanical stimuli and affect cell motility, adhesion and invasion of cancer cells. In nonmuscle cells, stress fibers have been subcategorized to three distinct stress fiber types: dorsal and ventral stress fibers and transverse arcs. These stress fibers are dissimilar in their subcellular localization, connection to substratum as well as in their dynamics and assembly mechanisms. Still uncharacterized is how they differ in their function and molecular composition. Here, I have studied involvement of nonmuscle alpha-actinin-1 and -4 in regulating distinct stress fibers as well as their localization and function in human U2OS osteosarcoma cells. Except for the correlation of upregulation of alpha-actinin-4 in invasive cancer types very little is known about whether these two actinins are redundant or have specific roles. The availability of highly specific alpha-actinin-1 antibody generated in the lab, revealed localization of alpha-actinin-1 along all three categories of stress fibers while alphaactinin-4 was detected at cell edge, distal ends of stress fibers as well as perinuclear regions. Strikingly, by utilizing RNAi-mediated gene silencing of alpha-actinin-1 resulted in specific loss of dorsal stress fibers and relocalization of alpha-actinin-4 to remaining transverse arcs and ventral stress fibers. Unexpectedly, aberrant migration was not detected in cells lacking alpha-actinin-1 even though focal adhesions were significantly smaller and fewer. Whereas, silencing of alpha-actinin-4 noticeably affected overall cell migration. In summary, as part of my master thesis study I have been able to demonstrate distinct localization and functional patterns for both alpha-actinin-1 and -4. I have identified alpha-actinin-1 to be a selective dorsal stress fiber crosslinking protein as well as to be required for focal adhesion maturation, while alpha-actinin-4 was demonstrated to be fundamental for cell migration.

The Evolving Roles of the Human Resource Function: Understanding Role Changes in the Context of Large-Scale Mergers

The human resource (HR) function is under pressure both to change roles and to play a large variety of roles. Questions of change and development in the HR function become particularly interesting in the context of mergers and acquisitions when two corporations are integrated. The purpose of the thesis is to examine the roles played by the HR function in the context of large-scale mergers and thus to understand what happens to the HR function in such change environments, and to shed light on the underlying factors that influence changes in the HR function. To achieve this goal, the study seeks first to identify the roles played by the HR function before and after the merger, and second, to identify the factors that affect the roles played by the HR function. It adopts a qualitative case study approach including ten focal case organisations (mergers) and four matching cases (non-mergers). The sample consists of large corporations originating from either Finland or Sweden. HR directors and members of the top management teams within the case organisations were interviewed. The study suggests that changes occur within the HR function, and that the trend is for the HR function to become increasingly strategic. However, the HR function was found to play strategic roles only when the HR administration ran smoothly. The study also suggests that the HR function has become more versatile. An HR function that was perceived to be mainly administrative before the merger is likely after the merger to perform some strategically important activities in addition to the administrative ones. Significant changes in the roles played by the HR function were observed in some of the case corporations. This finding suggests that the merger integration process is a window of opportunity for the HR function. HR functions that take a proactive and leading role during the integration process might expand the number of roles played and move from being an administrator before the merger to also being a business partner after integration. The majority of the HR functions studied remained mainly reactive during the organisational change process and although the evidence showed that they moved towards strategic tasks, the intra-functional changes remained comparatively small in these organisations. The study presents a new model that illustrates the impact of the relationship between the top management team and the HR function on the role of the HR function. The expectations held by the top management team for the HR function and the performance of the HR function were found to interact. On a dimension reaching from tactical to strategic, HR performance is likely to correspond to the expectations held by top management.

Collective Network Capability in International Project Business Networks - A Case Study of the Business Network for the Ashanti Electrification Project in Ghana

Despite thirty years of research in interorganizational networks and project business within the industrial networks approach and relationship marketing, collective capability of networks of business and other interorganizational actors has not been explicitly conceptualized and studied within the above-named approaches. This is despite the fact that the two approaches maintain that networking is one of the core strategies for the long-term survival of market actors. Recently, many scholars within the above-named approaches have emphasized that the survival of market actors is based on the strength of their networks and that inter-firm competition is being replaced by inter-network competition. Furthermore, project business is characterized by the building of goal-oriented, temporary networks whose aims, structures, and procedures are clarified and that are governed by processes of interaction as well as recurrent contracts. This study develops frameworks for studying and analysing collective network capability, i.e. collective capability created for the network of firms. The concept is first justified and positioned within the industrial networks, project business, and relationship marketing schools. An eclectic source of conceptual input is based on four major approaches to interorganizational business relationships. The study uses qualitative research and analysis, and the case report analyses the empirical phenomenon using a large number of qualitative techniques: tables, diagrams, network models, matrices etc. The study shows the high level of uniqueness and complexity of international project business. While perceived psychic distance between the parties may be small due to previous project experiences and the benefit of existing relationships, a varied number of critical events develop due to the economic and local context of the recipient country as well as the coordination demands of the large number of involved actors. The study shows that the successful creation of collective network capability led to the success of the network for the studied project. The processes and structures for creating collective network capability are encapsulated in a model of governance factors for interorganizational networks. The theoretical and management implications are summarized in seven propositions. The core implication is that project business success in unique and complex environments is achieved by accessing the capabilities of a network of actors, and project management in such environments should be built on both contractual and cooperative procedures with local recipient country parties.

Board Effectiveness in Small Firms

Purpose: This study investigates boards of directors in small firms and explores the link between board effectiveness and the composition, roles and working styles of the boards. Design/methodology/approach: The study analyses data from a telephone survey of boards in 45 small firms. The survey included both the CEO and the chairperson of the board. Findings: The study identifies three groups of small firms: ‘paperboards’, ‘professional boards’, and ‘management lead’ boards. Results show that board composition, board roles and board working style influence board effectiveness in small firms. Research limitations/implications: Although the present study has found a link between board effectiveness and the role, composition and working style of boards of small firms, other potentially influential factors are also worthy of investigation; for example, the personal characteristics of the individuals involved, generational factors in family firms, and the situational circumstances of various firms. Practical implications: The study reveals that, in practice, the management team and the board are substantially intertwined in small firms. Originality/value: The main contributions are that the study explores how boards in small firms actually function and gives a detailed account of their composition and roles.More insight into this issue is important given the overemphasis within the governance literature on input-output studies using samples of large publiclylisted firms.

Service Productivity: Toward a Conceptualisation of the Transformation of inputs

The productivity of a process is related to how effectively input resources are transformed into value for customers. For the needs of manufacturers of physical products there are widely used productivity concepts and measurements instruments. However, in service processes the underlying assumptions of these concepts and models do not hold. For example, manufacturing-based productivity models assume that an altered configuration of input resources in the production process does not lead to quality changes in outputs (the constant-quality assumption). However, in a service context changes in the production resources and productions systems do affect the perceived quality of services. Therefore, using manufacturing-oriented productivity models in service contexts are likely to give managers wrong directions for action. Research into the productivity of services is still scarce, because of the lack of viable models. The purpose of the present article is to analyse the requirements for the development of a productivity concept for service operations. Based on the analysis, a service productivity model is developed. According to this model, service productivity is a function of 1) how effectively input resources into the service (production) process are transformed to outputs in the form of services (internal or cost efficiency), 2) how well the quality of the service process and its outcome is perceived (external or revenue efficiency), and 3) how effectively the capacity of the service process is utilised (capacity efficiency). In addition, directions for developing measurement models for service productivity are discussed.

Methods in general model localization

The aim of this study was to evaluate and test methods which could improve local estimates of a general model fitted to a large area. In the first three studies, the intention was to divide the study area into sub-areas that were as homogeneous as possible according to the residuals of the general model, and in the fourth study, the localization was based on the local neighbourhood. According to spatial autocorrelation (SA), points closer together in space are more likely to be similar than those that are farther apart. Local indicators of SA (LISAs) test the similarity of data clusters. A LISA was calculated for every observation in the dataset, and together with the spatial position and residual of the global model, the data were segmented using two different methods: classification and regression trees (CART) and the multiresolution segmentation algorithm (MS) of the eCognition software. The general model was then re-fitted (localized) to the formed sub-areas. In kriging, the SA is modelled with a variogram, and the spatial correlation is a function of the distance (and direction) between the observation and the point of calculation. A general trend is corrected with the residual information of the neighbourhood, whose size is controlled by the number of the nearest neighbours. Nearness is measured as Euclidian distance. With all methods, the root mean square errors (RMSEs) were lower, but with the methods that segmented the study area, the deviance in single localized RMSEs was wide. Therefore, an element capable of controlling the division or localization should be included in the segmentation-localization process. Kriging, on the other hand, provided stable estimates when the number of neighbours was sufficient (over 30), thus offering the best potential for further studies. Even CART could be combined with kriging or non-parametric methods, such as most similar neighbours (MSN).

The function of NR3B and NR4A orphan nuclear receptors in osteoblasts

Nuclear receptors (NRs) comprise a large family of proteins that mediate the effects of small lipophilic molecules such as steroid hormones. In addition, there are a group of NRs which lack identified natural ligands and are referred as orphan NRs. In this thesis, the function of two such orphan NR families, the NR3B (ERRα, ERRβ and ERRγ) and the NR4A family (NGFI-B, Nurr1 and Nor1), was studied. NR3B and NR4A receptors regulate many biological processes such as energy metabolism and carcinogenesis. In addition, NR3B and NR4A receptors are expressed in bone. Therefore, the signaling and function of NR3B and NR4A orphan nuclear receptors was studied specifically in osteoblasts. NR4A receptors were found to be regulated by NR3B receptors and the Wnt/β-catenin signaling pathway as ERRα, ERRγ and β-catenin repressed the transcriptional activity of NR4A receptors in U2-OS cells. NGFI-B was found to repress the transcriptional activity of ERRγ in HeLa cells. The phytoestrogen equol was identified as a new agonist for ERRγ and ERRβ in PC-3, U2-OS, and SaOS-2 cells. Equol increased the transcriptional activity of ERRγ by increasing ERRγ co-activator binding and by inducing a conformational change in the ligand binding pocket of ERRγ. The growth inhibitory effect of equol on PC-3 prostate cancer cells was decreased by blocking ERRγ expression by siRNA. Therefore, ERRγ could mediate some of the beneficial health effects of equol. The Wnt/β-catenin signaling pathway is important for the differentiation and function of osteoblasts. NR3B and NR4A receptors were found to repress the transcriptional activity mediated by β-catenin in U2-OS cells. The mesenchymal stem cells (MSCs) isolated from ERRα knockout (KO) mice showed diminished proliferation and osteoblastic differentiation compared to the wild-type cells. The overexpression of ERRα in osteoblastic MC3T3-E1 cell line increased their mineralization. Bone sialoprotein (BSP) was shown to be a direct target gene for ERRα and ERRγ as the BSP promoter was activated by ERRα or ERRγ and PGC-1α in HeLa cells. The adipogenic differentiation of ERRα KO MSCs was also decreased and they expressed less adipogenic marker genes. In conclusion, the studies described in this thesis demonstrated that the transcriptional activity of NR3B and NR4A receptors can be regulated by other orphan NRs and signaling pathways in osteoblasts. NR3B receptors can also be regulated by ligands and a new agonist, equol, was identified for ERRβ and ERRγ. New roles for NR3B and NR4A were also identified as they were shown to converge with the Wnt signaling pathway in osteoblasts, ERRγ was shown to mediate the growth inhibitory effect of equol in prostate cancer cells, and ERRα was shown to regulate positively MSC proliferation, osteoblastic differentiation and adipogenesis.