Profound hyperglycemia in knockout mutant mice identifies novel function for POU4F2/Brn-3b in regulating metabolic processes.

The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of key metabolic processes. Loss of this protein in Brn-3b knockout (KO) mice causes profound hyperglycemia and insulin resistance (IR), normally associated with type 2 diabetes (T2D), whereas Brn-3b is reduced in tissues taken from obese mice fed on high-fat diets (HFD), which also develop hyperglycemia and IR. Furthermore, studies in C2C12 myocytes show that Brn-3b mRNA and proteins are induced by glucose but inhibited by insulin, suggesting that this protein is itself highly regulated in responsive cells. Analysis of differential gene expression in skeletal muscle from Brn-3b KO mice showed changes in genes that are implicated in T2D such as increased glycogen synthase kinase-3β and reduced GLUT4 glucose transporter. The GLUT4 gene promoter contains multiple Brn-3b binding sites and is directly transactivated by this transcription factor in cotransfection assays, whereas chromatin immunoprecipitation assays confirm that Brn-3b binds to this promoter in vivo. In addition, correlation between GLUT4 and Brn-3b in KO tissues or in C2C12 cells strongly supports a close association between Brn-3b levels and GLUT4 expression. Since Brn-3b is regulated by metabolites and insulin, this may provide a mechanism for controlling key genes that are required for normal metabolic processes in insulin-responsive tissues and its loss may contribute to abnormal glucose uptake.

Analysis of resuspension and sedimentation processes of unaltered fish faeces using image analysis

Postprint (published version)

The use of future-oriented knowledge in regional innovation processes: Research on knowledge generation, transfer and conversion

The importance of the regional level in research has risen in the last few decades and a vast literature in the fields of, for instance, evolutionary and institutional economics, network theories, innovations and learning systems, as well as sociology, has focused on regional level questions. Recently the policy makers and regional actors have also began to pay increasing attention to the knowledge economy and its needs, in general, and the connectivity and support structures of regional clusters in particular. Nowadays knowledge is generally considered as the most important source of competitive advantage, but even the most specialised forms of knowledge are becoming a short-lived resource for example due to the accelerating pace of technological change. This emphasizes the need of foresight activities in national, regional and organizational levels and the integration of foresight and innovation activities. In regional setting this development sets great challenges especially in those regions having no university and thus usually very limited resources for research activities. Also the research problem of this dissertation is related to the need to better incorporate the information produced by foresight process to facilitate and to be used in regional practice-based innovation processes. This dissertation is a constructive case study the case being Lahti region and a network facilitating innovation policy adopted in that region. Dissertation consists of a summary and five articles and during the research process a construct or a conceptual model for solving this real life problem has been developed. It is also being implemented as part of the network facilitating innovation policy in the Lahti region.

Managing the Front End of Innovation in a Networked Company Environment - Combining Strategy, Processes and Systems of Innovation

The objective of the thesis is to enhance the understanding about the management of the front end phases of the innovation process in a networked environment. The thesis approaches the front end of innovation from three perspectives, including the strategy, processes and systems of innovation. The purpose of the use of different perspectives in the thesis is that of providing an extensive systemic view of the front end, and uncovering the complex nature of innovation management. The context of the research is the networked operating environment of firms. The unit of analysis is the firm itself or its innovation processes, which means that this research approaches the innovation networks from the point of view of a firm. The strategy perspective of the thesis emphasises the importance of purposeful innovation management, the innovation strategy of firms. The role of innovation processes is critical in carrying out innovation strategies in practice, supporting the development of organizational routines for innovation, and driving the strategic renewal of companies. The primary focus of the thesis from systems perspective is on idea management systems, which are defined as a part of innovation management systems, and defined for this thesis as any working combination of methodology and tools (manual or IT-supported) that enhance the management of innovations within their early phases. The main contribution of the thesis are the managerial frameworks developed for managing the front end of innovation, which purposefully “wire” the front end of innovation into the strategy and business processes of a firm. The thesis contributes to modern innovation management by connecting the internal and external collaboration networks as foundational elements for successful management of the early phases of innovation processes in a dynamic environment. The innovation capability of a firm is largely defined by its ability to rely on and make use of internal and external collaboration already during the front end activities, which by definition include opportunity identification and analysis, idea generation, profileration and selection, and concept definition. More specifically, coordination of the interfaces between these activities, and between the internal and external innovation environments of a firm is emphasised. The role of information systems, in particular idea management systems, is to support and delineate the innovation-oriented behaviour and interaction of individuals and organizations during front end activities. The findings and frameworks developed in the thesis can be used by companies for purposeful promotion of their front end processes. The thesis provides a systemic strategy framework for managing the front end of innovation – not as a separate process, but as an elemental bundle ofactivities that is closely linked to the overall innovation process and strategy of a firm in a distributed environment. The theoretical contribution of the thesis relies on the advancement of the open innovation paradigm in the strategic context of a firm within its internal and external innovation environments. This thesis applies the constructive research approach and case study methodology to provide theoretically significant results, which are also practically beneficial.

Evolutionary Ecology of Mountain Birch in Subarctic Stress Gradients: Interplay of Biotic and Abiotic Factors in Plant-Plant Interactions and Evolutionary Processes

In nature, variation for example in herbivory, wind exposure, moisture and pollution impact often creates variation in physiological stress and plant productivity. This variation is seldom clear-cut, but rather results in clines of decreasing growth and productivity towards the high-stress end. These clines of unidirectionally changing stress are generally known as ‘stress gradients’. Through its effect on plant performance, stress has the capacity to fundamentally alter the ecological relationships between individuals, and through variation in survival and reproduction it also causes evolutionary change, i.e. local adaptations to stress and eventually speciation. In certain conditions local adaptations to environmental stress have been documented in a matter of just a few generations. In plant-plant interactions, intensities of both negative interactions (competition) and positive ones (facilitation) are expected to vary along stress gradients. The stress-gradient hypothesis (SGH) suggests that net facilitation will be strongest in conditions of high biotic and abiotic stress, while a more recent ‘humpback’ model predicts strongest net facilitation at intermediate levels of stress. Plant interactions on stress gradients, however, are affected by a multitude of confounding factors, making studies of facilitation-related theories challenging. Among these factors are plant ontogeny, spatial scale, and local adaptation to stress. The last of these has very rarely been included in facilitation studies, despite the potential co-occurrence of local adaptations and changes in net facilitation in stress gradients. Current theory would predict both competitive effects and facilitative responses to be weakest in populations locally adapted to withstand high abiotic stress. This thesis is based on six experiments, conducted both in greenhouses and in the field in Russia, Norway and Finland, with mountain birch (Betula pubescens subsp. czerepanovii) as the model species. The aims were to study potential local adaptations in multiple stress gradients (both natural and anthropogenic), changes in plant-plant interactions under conditions of varying stress (as predicted by SGH), potential mechanisms behind intraspecific facilitation, and factors confounding plant-plant facilitation, such as spatiotemporal, ontogenetic, and genetic differences. I found rapid evolutionary adaptations (occurring within a time-span of 60 to 70 years) towards heavy-metal resistance around two copper-nickel smelters, a phenomenon that has resulted in a trade-off of decreased performance in pristine conditions. Heavy-metal-adapted individuals had lowered nickel uptake, indicating a possible mechanism behind the detected resistance. Seedlings adapted to heavy-metal toxicity were not co-resistant to others forms of abiotic stress, but showed co-resistance to biotic stress by being consumed to a lesser extent by insect herbivores. Conversely, populations from conditions of high natural stress (wind, drought etc.) showed no local adaptations, despite much longer evolutionary time scales. Due to decreasing emissions, I was unable to test SGH in the pollution gradients. In natural stress gradients, however, plant performance was in accordance with SGH, with the strongest host-seedling facilitation found at the high-stress sites in two different stress gradients. Factors confounding this pattern included (1) plant size / ontogenetic status, with seedling-seedling interactions being competition dominated and host-seedling interactions potentially switching towards competition with seedling growth, and (2) spatial distance, with competition dominating at very short planting distances, and facilitation being strongest at a distance of circa ¼ benefactor height. I found no evidence for changes in facilitation with respect to the evolutionary histories of plant populations. Despite the support for SGH, it may be that the ‘humpback’ model is more relevant when the main stressor is resource-related, while what I studied were the effects of ‘non-resource’ stressors (i.e. heavy-metal pollution and wind). The results have potential practical applications: the utilisation of locally adapted seedlings and plant facilitation may increase the success of future restoration efforts in industrial barrens as well as in other wind-exposed sites. The findings also have implications with regard to the effects of global change in subarctic environments: the documented potential by mountain birch for rapid evolutionary change, together with the general lack of evolutionary ‘dead ends’, due to not (over)specialising to current natural conditions, increase the chances of this crucial forest-forming tree persisting even under the anticipated climate change.