Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation

Plasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition. In addition to TGF-β receptor kinase inhibitors, we identified small molecule epithelial plasticity modulators including a naturally occurring hydroxysterol agonist of the liver X receptors (LXRs), members of the nuclear receptor transcription factor family. Endogenous and synthetic LXR agonists tested in diverse cell models blocked α-smooth muscle actin expression, myofibroblast differentiation and function. Agonist-dependent LXR activity or LXR overexpression in the absence of ligand counteracted TGF-β-mediated myofibroblast terminal differentiation and collagen contraction. The protective effect of LXR agonists against TGF-β-induced pro-fibrotic activity raises the possibility that anti-lipidogenic therapy may be relevant in fibrotic disorders and advanced cancer

The conditioning regime in industrial drying of Scots pine sawn timber studied by X-ray computed tomography : a case-study

Industrial drying of sawn timber is a process driven by a difference in moisture content (MC) between the core and the surface as moisture moves from the wet inner region towards the drier surface. After drying, the timber surface is always drier than its core, and stresses have developed within the wood volume. If the timber is to be further processed, these stresses and the moisture gradient need to be reduced to avoid unwanted distortion, i.e. the timber needs to be conditioned. Conditioning is usually accomplished by exposing the timber to a hot and humid climate after the drying regime. The conditioning regime is essential for timber quality, and it is energy and time consuming; therefore of interest for optimisation. This research was a case study where for the first time the MC during conditioning was studied in an X-ray computed tomography (CT) scanner. The aim was to test a previously developed algorithm and investigate the influence of MC and heartwood-sapwood proportion on the effectivity of the moisture equalisation in 30 mm thick Scots pine boards. The MC was estimated from CT data acquired during the drying and conditioning of the boards in a lab-scale kiln adapted to a medical CT scanner. Results show that the algorithm can provide relevant data of internal MC distribution of sawn timber at the pixel level. Furthermore, for the drying schedules studied, the conditioning at low MC (8%) does not need to be longer than 3 h, while higher MC (18%) requires a longer conditioning

Protein/Emulsifier Interactions

An important consequence of protein-lipid interaction is the effect on stability of the protein in solution as well as on its behavior at interfaces. Here we will discuss key aspects of protein aggregation and unfolding as well as the effects of protein structure (random coil proteins versus globular) that are relevant for our understanding protein-lipid interaction. The main types of emulsifiers are the (1) aqueous soluble, surfactant type and (2) lipids with low aqueous solubility. The monomer concentration as defined by cmc is an important parameter for the soluble lipids. For emulsifiers with low aqueous solubility the emulsifier self-assembly structure and its properties control the interaction with proteins. We will therefore summarize the main features of lipid self-assembly. It also allows us to define different plausible scenarios and principles and models for factors that control the interactions in real food (and Pharmaceutical) systems. For the food applications the fate of the lipid during digestion is important and therefore we will discuss some aspects of enzyme-catalyzed lipolysis in terms of the structural evolution. New products and concepts of using protein/emulsifier interactions will be exemplified by illustrating how food nanotechnology possibly can be used for the delivery of functionality