Genetic regulatory networks in avian B cells

Biology is turning into an information science. The science of systems biology seeks to understand the genetic networks that govern organism development and functions. In this study the chicken was used as a model organism in the study of B cell regulatory factors. These studies open new avenues for plasma cell research by connecting the down regulation of the B cell gene expression program directly to the initiation of plasma cell differentiation. The unique advantages of the DT40 avian B cell model system, specifically its high homologous recombination rate, were utilized to study gene regulation in Pax5 knock out cell lines and to gain new insights into the B cell to plasma cell transitions that underlie the secretion of antibodies as part of the adaptive immune response. The Pax5 transcription factor is central to the commitment, development and maintenance of the B cell phenotype. Mice lacking the Pax5 gene have an arrest in development at the pro-B lymphocyte stage while DT40 cells have been derived from cells at a more mature stage of development. The DT40 Pax5-/- cells exhibited gene expression similarities with primary chicken plasma cells. The expression of the plasma cell transcription factors Blimp-1 and XBP-1 were significantly upregulated while the expression of the germinal centre factor BCL6 was diminished in Pax5-/- cells, and this alteration was normalized by Pax5 re-introduction. The Pax5-deficient cells further manifested substantially elevated secretion of IgM into the supernatant, another characteristic of plasma cells. These results for the first time indicated that the downregulation of the Pax5 gene in B cells promotes plasma cell differentiation. Cross-species meta-analysis of chicken and mouse Pax5 gene knockout studies uncovers genes and pathways whose regulatory relationship to Pax5 has remained unchanged for over 300 million years. Restriction of the hematopoietic stem cell fate to produce T, B and NK cell lineages is dependent on the Ikaros and its molecular partners, the closely related Helios and Aiolos. Ikaros family members are zinc finger proteins which act as transcriptional repressors while helping to activate lymphoid genes. Helios in mice is expressed from the hematopoietic stem cell level onwards, although later in development its expression seems to predominate in the T cell lineage. This study establishes the emergence and sequence of the chicken Ikaros family members. Helios expression in the bursa of Fabricius, germinal centres and B cell lines suggested a role for Helios in the avian B-cell lineage, too. Phylogenetic studies of the Ikaros family connect the expansion of the Ikaros family, and thus possibly the emergence of the adaptive immune system, with the second round of genome duplications originally proposed by Ohno. Paralogs that have arisen as a result of genome-wide duplications are sometimes termed ohnologs – Ikaros family proteins appear to fit that definition. This study highlighted the opportunities afforded by the genome sequencing efforts and somatic cell reverse genetics approaches using the DT40 cell line. The DT40 cell line and the avian model system promise to remain a fruitful model for mechanistic insight in the post-genomic era as well.

Role of culture in knowledge transfer and sharing - case ERP implementation

The main objective of this study was to examine how culture influences knowledge transfer and sharing within multicultural ERP project implementation in China. The main interest was to explain how national culture and knowledge are linked by understanding how culture influences knowledge transfer and sharing in a project organization. The other objective of this work was to discuss what Chinese cultural characteristic inhibit and en-hance knowledge sharing in ERP project. The perspective of this study was qualitative and the empirical material was collected from theme interviews among Stora Enso employees. Conclusion of this thesis is that Finns have a very direct style of communication and sharing knowledge whereas Chinese respect face shaving and indirect communication. Another conclusion is that knowledge sharing does not “just happen”, it is needed that project members understand national culture to get all project members commitment to project. In China most important is understand local business processes and understand role of trust and guanxi.

Energia-auditointipalveluprosessin kehittäminen

Pro gradu -tutkielman tavoitteena on kehittää LUT Energian tarjoamia energia-auditointipalveluja tuotteistamisen myötä. Lisäksi tarkoitus on selvittää, miten tietoa voidaan siirtää palveluprosessien välillä ja täten kehittää palvelun jatkuvuutta sekä markkinointia. Laadullinen tutkimus toteutettiin keräämällä esitutkimusmateriaali kyselyjen avulla ja varsinainen tutkimusaineisto teemahaastatteluilla. Haastattelujen kohteena olivat palvelun hankkineet yritykset ja palvelua tuottaneet opiskelijat. Tutkimuksen tuloksena energia-auditointipalvelussa havaittiin useita merkittäviä kehittämiskohteita. Kehittämiskohteet liittyvät kuuteen eri teemaan: palveluprosessin alkuvaiheeseen, aikatauluun, luottamukseen ja sitoutumiseen, palvelun markkinointiin ja palvelun jatkuvuuteen. Aineiston pohjalta luotiin kohdeyritykselle konkreettisia toimenpide-ehdotuksia, joiden avulla palveluprosessia voidaan tulevaisuudessa kehittää ja sen laatua parantaa. Palvelun hallittavuus ja jatkuvuuden edellytykset paranevat tutkimustulosten myötä.

Cultural aspects of globalizing university-industry knowledge interaction in China

Previous studies of the local involvement of multinational corporation (MNC) subsidiaries focus on host-country firms and local business partners such as suppliers and customers. The role of host-country universities in the same context of innovation networks is neglected. Furthermore, there are many organizational culture- and knowledge-related differences between universities and companies, and this is likely to pose additional challenges for successful collaboration. Early university-industry (U-I) studies have primarily been limited within a national boundary, being concerned with a single level of culture (i.e., at an organizational level) and one-way knowledge transfer from university to industry. Research on more dynamic knowledge interaction in multinational settings is lacking. This is particularly true in the business context of China. In today’s globalizing and rapidly changing organizations, addressing cultural differences and clashes is an everyday reality, and inter-cultural U-I collaboration is becoming a key asset for gaining global competitiveness. This study deals with Finnish MNC subsidiaries’ research collaboration with Chinese universities. It aims to explore the essence of such U-I collaboration and knowledge interaction, uncovering the deep functioning mechanisms of culture underlying effective collaborative knowledge creation and innovation. The study reviews critically different bodies of literature including knowledge management theories and studies, U-I collaboration and knowledge interaction, and cross-cultural research in terms of organizational knowledge generation and utilization. It adopts a case study strategy with qualitative research methods, and data is collected through in-depth interviews and participant observation. The study presents the following major findings: 1. In the light of a comprehensive analysis of U-I collaboration, an effective matching strategy is proposed, in the assumption that good alignment of knowledge interaction strategies and approaches with their corresponding knowledge type, capability development and research task may greatly enhance the effectiveness of cross-cultural U-I collaboration and knowledge interaction. 2. It is proposed that in the Chinese MNC context more dynamic types of knowledge interaction like knowledge co-creation should be of key concern particularly when dealing simultaneously with multi-disciplinary applied research of human factors and technologies. U-I knowledge interaction, otherwise, pays attention only to the study of one-way technology and knowledge transfer. 3. It is posited that the influence of culture on collaborative knowledge interaction can be studied in a valuable way when knowledge-related variables are simultaneously taken into account. A systematic analysis of the role of knowledge in cross-cultural knowledge interaction could best be approached from multi-aspects of knowledge including not only nature, characteristics and types of knowledge but also the process of knowledge (e.g., intensifications of knowledge interaction). 4. The study demonstrates the significant role of aspects of the host-country culture (e.g., Chinese guanxi) in U-I collaboration and knowledge interaction. This is evident, for instance, in issues related to interpersonal relationships and trust, true interest and the relatedness of the research, mutual commitment and learning, communication intensity and interaction, and awareness of cultural and knowledge-related differences between collaboration partners. Theoretical and practical implications of the findings are suggested and discussed.

Luottamuksen rooli hiljaisen tietämyksen jakamisessa

Pro gradu – tutkielman tavoitteena oli tutkia luottamuksen roolia hiljaisen tietämyksen jakamisessa. Työn teoreettisena tavoitteena oli selvittää luottamuksen tukemisen ja rakentamisen keinoja hiljaisen tietämyksen jakamisen tueksi yhdistämällä hiljaista tietämystä ja luottamusta koskeva kirjallisuus. Empiirisen tutkimuksen tavoitteena oli tuoda teoria käytännön tasolle ja selvittää miten hiljaisen tietämyksen jakamista voidaan edistää luottamuksen avulla. Tässä tutkimuksessa on käytetty menetelmätriangulaatiota empiirisen aineiston tutkimusmenetelmänä yhdistämällä kvalitatiivinen ja kvantitatiivinen tutkimusote. Tutkimusaineisto kerättiin haastattelujen ja kyselyn avulla. Empiirisen tutkimuksen kohteena oli hiljaisen tietämyksen jakaminen tiimikontekstissa ja luottamuksen rooli siinä. Tutkimuksen perusteella saatiin selkeä kuva siitä, mihin hiljaisen tietämyksen jakamisen tekijöihin luottamus vaikuttaa ja millaisia seuraamuksia luottamuksella on hiljaisen tietämyksen jakamiseen. Tutkimuksen tulokset tukivat aiempia empiirisiä tutkimustuloksia tunnepohjaisen ja järkiperäisen luottamuksen osalta. Tässä tutkimuksessa tulokset myös osoittivat, että luottamuksen merkitys tiimin toimintaan, hiljaisen tietämyksen jakamiseen, yhteistyöhön, sitoutumiseen sekä motivaatioon on merkittävä. Tämä on hyvä tiedostaa ja siihen tulee kiinnittää tietoisesti huomiota koko organisaation kehittämisen työkaluna.

Factors Regulating Chondrogenic Differentiation

Chondrogenesis is a co-ordinated differentiation process in which mesenchymal cells condensate, differentiate into chondrocytes and begin to secrete molecules that form the extracellular matrix. It is regulated in a spatio-temporal manner by cellular interactions and growth and differentiation factors that modulate cellular signalling pathways and transcription of specific genes. Moreover, post-transcriptional regulation by microRNAs (miRNAs) has appeared to play a central role in diverse biological processes, but their role in skeletal development is not fully understood. Mesenchymal stromal cells (MSCs) are multipotent cells present in a variety of adult tissues, including bone marrow and adipose tissue. They can be isolated, expanded and, under defined conditions, induced to differentiate into multiple cell lineages including chondrocytes, osteoblasts and adipocytes in vitro and in vivo. Owing to their intrinsic capability to self-renew and differentiate into functional cell types, MSCs provide a promising source for cell-based therapeutic strategies for various degenerative diseases, such as osteoarthritis (OA). Due to the potential therapeutic applications, it is of importance to better understand the MSC biology and the regulatory mechanisms of their differentiation. In this study, an in vitro assay for chondrogenic differentiation of mouse MSCs (mMSCs) was developed for the screening of various factors for their chondrogenic potential. Conditions were optimized for pellet cultures by inducing mMSC with different bone morphogenetic proteins (BMPs) that were selected based on their known chondrogenic relevance. Characterization of the surface epitope profile, differentiation capacity and molecular signature of mMSCs illustrated the importance of cell population composition and the interaction between different populations in the cell fate determination and differentiation of MSCs. Regulation of Wnt signalling activity by Wnt antagonist sFRP-1 was elucidated as a potential modulator of lineage commitment. Delta-like 1 (dlk1), a factor regulating adipogenesis and osteogenesis, was shown to exhibit stage-specific expression during embryonic chondrogenesis and identified as a novel regulator of chondrogenesis, possibly through mediating the effect of TGF-beta1. Moreover, miRNA profiling demonstrated that MSCs differentiating into a certain lineage exhibit a specific miRNA expression profile. The complex regulatory network between miRNAs and transcription factors is suggested to play a crucial role in fine-tuning the differentiation of MSCs. These results demonstrate that commitment of mesenchymal stromal cells and further differentiation into specific lineages is regulated by interactions between MSCs, various growth and transcription factors, and miRNA-mediated translational repression of lineage-specific genes.