Advanced Computational Biology Methods Identify Molecular Switches for Malignancy in an EGF Mouse Model of Liver Cancer

The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification

Retinal and olfactory bulb precursor cells show distinct responses to FGF-2 and laminin

We analyzed whether the embryonic (E12.5-E14.5) mouse retina possesses genuine neural stem cells and how they respond to defined growth factors and extracellular matrix molecules. Whereas most combinations produced no or limited cell survival and proliferation in culture, FGF-2 plus heparin and laminin stimulated proliferation and the formation of aggregates composed, after two days, of 95.2% nestin-positive cells. However, cells in these aggregates could only be passaged poorly, lost nestin expression and proliferative capacity, and differentiated into neurons. Under the same conditions, olfactory bulb precursor cells divided efficiently and could be expanded. These data suggest that, in addition to FGF-2 and laminin, embryonic retinal neuroepithelial cells need additional extrinsic and/or intrinsic regulators to maintain cell proliferation and self-renewal. © 2006 International Federation for Cell Biology.Peer Reviewe

Mechanical, electrical, and adhesive synergies in melt-processed hybrid bio-based TPU nanocomposites

Hybrid nanocomposites (NCs) based on a bio-based thermoplastic polyurethane (TPU) with multi-walled carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs) as nanofillers, were obtained using a simple melt-mixing method. The effects of a) the GNP:CNT ratio, b) the total nanofiller content, and c) the aspect ratio of the CNTs on both the nanostructure and the thermal, electrical, mechanical, and adhesive properties of the NCs were studied in depth. Synergies were observed in the mechanical and electrical properties of the hybrid NCs when compared to the corresponding binary TPU/GNP and TPU/CNT NCs, regardless of either the GNP:CNT ratio or the aspect ratio of the CNTs. This was attributed to the enhanced dispersion of the GNPs in the presence of CNTs, caused by the intercalation of the two-dimensional graphene nanoplatelets among the one-dimensional carbon nanotubes. Consequently, the resulting conductive network was more efficient, and the reinforcing efficiency of the single nanofillers was improved. The findings of our study show that electrically conductive NCs with improved mechanical properties were achieved when part of the CNTs in the formulation was replaced by cheaper GNPs. Furthermore, a synergy was also observed in the adhesive properties of the hybrid NCs through their significantly higher lap shear strength than that of the pure TPU or binary reference NCs. In other words, by replacing part of the CNTs with GNPs, we were able to obtain hybrid TPU NCs which were cheaper, more effective, and higher performing than binary TPU/CNT and TPU/GNP NCs, pointing to their potential use as electrically conductive hot-melt adhesives

Effect of compatibilizer addition on the surface nucleation of dispersed polyethylene droplets in a self-nucleated polypropylene matrix

A significant portion of the global plastics market encompasses the production of polyolefin materials and especially polypropylene (PP) and polyethylene (PE), as commodity polymers with a wide range of applications. However, the increase in the generation of unsustainable plastic waste requires a close technological look-up to address this challenge adequately. In this context, mechanical recycling is part of the strategies expected to contribute to the solution. Nevertheless, the melt blending process presents a challenge due to the immiscibility between PP and PE. Therefore, compatibilization strategies are meant to solve the problem effectively. In this paper, we employ a commercial ethylene-ran-methyl acrylate random copolymer as a compatibilizer for PP/PE blends. With the addition of the compatibilizer, it was possible to obtain a 44% reduction in PE domain size, while ductility increased by around similar to 40% with respect to uncompatibilized blends. Interesting results were obtained concerning the crystallization behavior of the blends. The overall isothermal crystallization kinetics of the different blend components was studied, and a synergistic nucleation effect of the PP and the compatibilizer toward the PE phase was found. For the first time, the effect of the compatibilizer on the surface nucleation of PE in a self-nucleated PP matrix phase is reported. An enhancement in the crystallization rate of PE was found when the self-nucleation protocol was applied to the polypropylene matrix phase for neat and compatibilized blends. The nucleation efficiency was in the range of 120-124%, indicating a supernucleation behavior. The induced crystallization at the interface by the self-nucleated polypropylene is the reason for such high nucleation efficiencies. Surprisingly, a higher amount of compatibilizer decreases the overall crystallization rate of PE droplets. The compatibilizer segregates at the interface between both polymers, reducing the surface nucleation of the PE droplets on the PP matrix phase. The results presented in this paper lead the way toward improving the use of post-consumer recycled materials