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A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at −80 °C consumes as much energy per day as a small household1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose2, sucrose or polymers3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze–thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.A stiff hydrogel gel is presented that encapsulates and stabilizes proteins without additives or excipients and uses mechanical strain to release them, offering low-cost and versatile delivery of therapies. [ABSTRACT FROM AUTHOR]

The Drosophila tumour suppressors Scribbled and Discs large 1 are found to be essential regulators of planar spindle alignment during epithelial cell division; aberrant effects of spindle alignment are shown to be corrected through apoptosis, and the suppression of this mechanism can result in epithelial dysplasia and tumorigenesis. Discs large, Scribbled involved in spindle alignment Mitotic spindle formation is a key step towards the segregation of chromosomes into two daughter cells during mitosis, and the precise alignment of mitotic spindles to the plane of the epithelium is thought to be important in maintaining tissue integrity. The in vivo determinants of planar spindle orientation remain unknown. Here Matthew Gibson and colleagues demonstrate that the actomyosin cortex and junction-localized tumour suppressors Scribbled and Discs large 1 are essential regulators of planar spindle alignment. Defective alignment of the mitotic spindle correlates with cell delamination and apoptotic death, and furthermore, blocking death of misaligned cells is sufficient to drive the formation of tumour-like cell masses. The authors propose that the deleterious effects of aberrant spindle alignment are corrected by apoptosis and that suppression of this mechanism could result in epithelial dysplasia and tumorigenesis. During epithelial cell proliferation, planar alignment of the mitotic spindle coordinates the local process of symmetric cell cleavage with the global maintenance of polarized tissue architecture.sup.1,2. Although the disruption of planar spindle alignment is proposed to cause epithelial to mesenchymal transition and cancer.sup.3,4,5,6, the in vivo mechanisms regulating mitotic spindle orientation remain elusive. Here we demonstrate that the actomyosin cortex and the junction-localized neoplastic tumour suppressors Scribbled and Discs large 1 have essential roles in planar spindle alignment and thus the control of epithelial integrity in the Drosophila imaginal disc. We show that defective alignment of the mitotic spindle correlates with cell delamination and apoptotic death, and that blocking the death of misaligned cells is sufficient to drive the formation of basally localized tumour-like masses. These findings indicate a key role for junction-mediated spindle alignment in the maintenance of epithelial integrity, and also reveal a previously unknown cell-death-mediated tumour-suppressor function inherent in the polarized architecture of epithelia., Author(s): Yu-ichiro Nakajima [sup.1] , Emily J. Meyer [sup.1] , Amanda Kroesen [sup.1] , Sean A. McKinney [sup.1] , Matthew C. Gibson [sup.1] [sup.2] Author Affiliations: (1) Stowers Institute for [...]