Effect of homogenisation conditions on recrystallisation in the Al-Mg-Mn alloy AA5454

The purpose of the present work is to understand the microstructure development and, particularly, to control the progress of recrystallisation in hot strip in the Al-Mg-Mn alloy AA 5454, which is typically used for the manufacture of structural automotive components. The chemical composition, together with the thermomechanical processing history of this material, has a strong influence on the microstructure of the product and the resulting properties as it is supplied to the customer. Electrical conductivity measurements, thermal analysis and electron microscopy have been carried out to characterise the evolution of precipitation state at various stages in the processing route. The conditions of the homogenisation heat treatment have been varied, and the effect on subsequent recrystallisation after hot rolling has been evaluated in both the as cast and rough rolled condition by optical microscopy techniques. Results indicate that the conditions of homogenisation heat treatment and roughing rolling are critical for the generation of a suitable recrystallised microstructure in AA 5454 hot strip. A new two stage homogenisation practice has been developed to expedite post-rolling recrystallisation in this alloy

Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling

Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors. As a result of their acylation, Wnt proteins are very hydrophobic and require detergents for purification, which presents major obstacles to the preparation and application of recombinant Wnt proteins. This hydrophobicity has hindered the determination of the molecular mechanisms of Wnt signalling activation and the functional importance of FZD subtypes, and the use of Wnt proteins as therapeutic agents. Here we develop surrogate Wnt agonists, water-soluble FZD-LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains. Similar to WNT3A, these Wnt agonists elicit a characteristic β-catenin signalling response in a FZD-selective fashion, enhance the osteogenic lineage commitment of primary mouse and human mesenchymal stem cells, and support the growth of a broad range of primary human organoid cultures. In addition, the surrogates can be systemically expressed and exhibit Wnt activity in vivo in the mouse liver, regulating metabolic liver zonation and promoting hepatocyte proliferation, resulting in hepatomegaly. These surrogates demonstrate that canonical Wnt signalling can be activated by bi-specific ligands that induce receptor heterodimerization. Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine