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Leivonen S.K.,VTT Technical Research Center of Finland
Molecular & cellular proteomics : MCP | Year: 2011

Identification of protein targets for microRNAs (miRNAs) is a significant challenge due to the complexity of miRNA-mediated regulation. We have previously demonstrated that miR-193b targets estrogen receptor-α (ERα) and inhibits estrogen-induced growth of breast cancer cells. Here, we applied a high-throughput strategy using quantitative iTRAQ (isobaric tag for relative and absolute quantitation) reagents to identify other target proteins regulated by miR-193b in breast cancer cells. iTRAQ analysis of pre-miR-193b transfected MCF-7 cells resulted in identification of 743 unique proteins, of which 39 were down-regulated and 44 up-regulated as compared with negative control transfected cells. Computationally predicted targets of miR-193b were highly enriched (sevenfold) among the proteins whose level of expression decreased after miR-193b transfection. Only a minority of these (13%) showed similar effect at the mRNA level illustrating the importance of post-transcriptional regulation. The most significantly repressed proteins were selected for validation experiments. These data confirmed 14-3-3ζ (YWHAZ), serine hydroxyl transferase (SHMT2), and aldo-keto reductase family 1, member C2 (AKR1C2) as direct, previously uncharacterized, targets of miR-193b. Functional RNAi assays demonstrated that specific combinations of knockdowns of these target genes by siRNAs inhibited growth of MCF-7 cells, mimicking the effects of the miR-193b overexpression. Interestingly, the data imply that besides targeting ERα, the miR-193b effects include suppression of the local production of estrogens and other steroid hormones mediated by the AKR1C2 gene, thus provoking two separate molecular mechanisms inhibiting steroid-dependent growth of breast cancer cells. In conclusion, we present here a proteomic screen to identify targets of miR-193b, and a systems biological approach to mimic its effects at the level of cellular phenotypes. This led to the identification of multiple genes whose combinatorial knock-down likely mediates the strong anti-cancer effects observed for miR-193b in breast cancer cells. Source


Karjalainen S.,VTT Technical Research Center of Finland
Energy and Buildings | Year: 2011

Numerous studies have shown that feedback on energy consumption can work to effectively reduce household energy consumption. However, relatively little work has been done on the best ways to present information in order to maximise energy savings. In this work, different ways of presenting feedback on electricity consumption were systematically analysed and user interface prototypes were developed based on the analysis. The prototypes were shown to consumers in qualitative interviews to gain information on how well they understood them and what kind of feedback they prefer to receive on their electricity consumption. The results show that the following features of feedback on electricity consumption are most valued by consumers: presentations of costs (over a period of time), appliance-specific breakdown, i.e. information on what proportion is consumed by each appliance, and historical comparison, i.e. comparison with their own prior consumption. © 2010 Elsevier B.V. All rights reserved. Source


Ivaska J.,VTT Technical Research Center of Finland
Nature Cell Biology | Year: 2012

Focal adhesions are large structures through which integrins and scaffold proteins link the actin cytoskeleton to the extracellular matrix. A detailed analysis of integrin dynamics now indicates that focal-adhesion-associated integrins constantly switch between active and immobilized, and unbound and free-diffusing states, with different fibronectin-binding integrin heterodimers showing distinct focal-adhesion dynamics. © 2012 Macmillan Publishers Limited. All rights reserved. Source


Haapio A.,VTT Technical Research Center of Finland
Environmental Impact Assessment Review | Year: 2012

Requirements for the assessment tools of buildings have increased, assessing of building components or separate buildings is not enough. Neighbourhoods, built environment, public transportations, and services, should be considered simultaneously. Number of population living in urban areas is high and increasing rapidly. Urbanisation is a major concern due to its detrimental effects on the environment. The aim of this study is to clarify the field of assessment tools for urban communities by analysing the current situation. The focus is on internationally well known assessment tools; BREEAM Communities, CASBEE for Urban Development and LEED for Neigborhood Development.The interest towards certification systems is increasing amongst the authorities, and especially amongst the global investors and property developers. Achieved certifications are expected to bring measureable publicity for the developers. The assessment of urban areas enables the comparison of municipalities and urban areas, and notably supports decision making processes. Authorities, city planners, and designers would benefit most from the use of the tools during the decision making process. © 2011 Elsevier Inc. Source


Oresic M.,VTT Technical Research Center of Finland
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2011

The ability to translate vast amounts of information, as obtained from lipidomic analysis, into the knowledge and understanding of biological phenomena is an important challenge faced by the lipidomics community. While many of the informatics and computational tools from other domains such as bioinformatics and metabolomics are also applicable to lipidomics data processing and analysis, new solutions and strategies are needed for the studies of lipidomes at the systems level. This is due to enormous functional and structural diversity of lipids as well as because of their complex regulation at multiple spatial and temporal scales. In order to better understand the lipidomes at the physiological level, lipids need to be modeled not only at the level of biological pathways but also at the level of the biophysical systems they are part of, such as cellular membranes or lipoprotein particles. Herein the current state, recent advances and new opportunities in the field of lipid bioinformatics are reviewed. This article is part of a Special Issue entitled Lipodomics and Imaging Mass Spectrometry. © 2011 Elsevier B.V. Source

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