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© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. Neovascularization, increased basal membrane thickness and increased airway smooth muscle (ASM) bulk are hallmarks of airway remodelling in asthma. In this study, we examined connective tissue growth factor (CTGF) dysregulation in human lung tissue and animal models of allergic airway disease. Immunohistochemistry revealed that ASM cells from patients with severe asthma (A) exhibited high expression of CTGF, compared to mild and non-asthmatic (NA) tissues. This finding was replicated in a sheep model of allergic airways disease. In vitro, transforming growth factor (TGF)-β increased CTGF expression both in NA- and A-ASM cells but the expression was higher in A-ASM at both the mRNA and protein level as assessed by PCR and Western blot. Transfection of CTGF promoter-luciferase reporter constructs into NA- and A-ASM cells indicated that no region of the CTGF promoter (−1500 to +200 bp) displayed enhanced activity in the presence of TGF-β. However, in silico analysis of the CTGF promoter suggested that distant transcription factor binding sites may influence CTGF promoter activation by TGF-β in ASM cells. The discord between promoter activity and mRNA expression was also explained, in part, by differential post-transcriptional regulation in A-ASM cells due to enhanced mRNA stability for CTGF. In patients, higher CTGF gene expression in bronchial biopsies was correlated with increased basement membrane thickness indicating that the enhanced CTGF expression in A-ASM may contribute to airway remodelling in asthma.

On the basis of our recently resolved first cocrystal structure of Mdm4 in complex with a small molecule inhibitor (PDB ID 3LBJ ), we devised an approach for the generation of potential Mdm4 selective ligands. We performed the Ugi four-component reaction (Ugi-4CR) in 96-well plates with an indole fragment, which is specially designed to mimic Trp23, a key amino acid for the interaction between p53 and Mdm4. Generally the reaction yielded mostly precipitates collected by 96-well filter plates. The best hit compound was found to be active and selective for Mdm4 (Ki = 5 μM, 10-fold stronger than Mdm2). This initial hit may serve as the starting point for designing selective p53-Mdm4 inhibitor with higher affinity.

This book originates from observations that whilst an increasing body of scholars and students are using geographical information and computing technologies (geo-ICT) across a widening range of academic disciplines, there is relatively little systematic knowledge about the way in which these technologies are being used or the impact that the adoption of geo-ICT is making on each discipline. In this introductory chapter, we set the scene by explaining our definition of geo-ICT and acknowledging the increasing importance of spatial concepts in scientific research. Thereafter, we review how scientific practice changes over time before explaining the structure of the book and outlining the key questions that contributors were asked to address which underline the two main aims of the book: to increase knowledge of the current use of Geo-ICT in scientific research and to come up with (methodological) strategies to promote more effective use of geo-ICT in the future.

Location is a fundamental aspect of spatial planning. It is subject to, and the result of, planning activities. It is therefore not surprising that the first incentives for the development of tools for spatial data management and spatial analysis came from professionals who were engaged in spatial planning. This chapter describes the development and interaction between the evolvement of spatial planning and the rapid development of Geo-ICT in the past decades. This is illustrated with examples of Geo-ICT applications used for spatial planning over the years, from very basic land use models via more advanced models to integrated systems supporting discussion and decision making. Key issues as the growing importance of the communicative aspects of planning processes and the concept of planning as a participatory process are adressed. Through the revolutionary development of internet technology along with geospatial technology new future crossroads between Geo-ICT and spatial planning are foreseen. Although Geo-ICT and spatial planning appear to be closely related interrelated in scientific development, it is stated that the use of Geo-ICT in spatial planning practice lags behind expectations. The key obstacles related to this in methodology, data and competences are reviewed.

In many industrialised countries, there have been significant changes in land use as a consequence of development processes. In the long term, more and more land has been used for urban and agricultural purposes. More recently, however, whilst the total area committed to urban land use has continued to increase, overproduction and intensification trends have led to a decline in the amount of agricultural land required. Moreover, the area of ‘natural’ land has increased in some countries in response to policies implemented by public and private agencies. The impact of different planning concepts on the land market, the environment and the urban and rural landscape can differ significantly. Scarcities of space, conflicting land use types as well as multi-actor decision-making have contributed to the increasing complexity within the planning process. Present planning methods lack the capacity to take different sources of (spatial) information into account and thus neglect the complexity of land use planning and development.

In deze rapportage hebben we ons verdiept in de wereld van de commerciële toepassingen van sensordata, waarin locatiegegevens van smartphones op grote schaal worden vastgelegd. Een beter inzicht in de wereld van de sociale en commerciële platforms zou ervoor moeten zorgen dat deze beter begrepen wordt door de geosector.