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The geometric phase provides important mathematical insights to understand the fundamental nature and evolution of the dynamic response in a wide spectrum of systems ranging from quantum to classical mechanics. While the concept of geometric phase, which is an additional phase factor occurring in dynamical systems, holds the same meaning across different fields of application, its use and interpretation can acquire important nuances specific to the system of interest. In recent years, the development of quantum topological materials and its extension to classical mechanical systems have renewed the interest in the concept of geometric phase. This review revisits the concept of geometric phase and discusses, by means of either established or original results, its critical role in the design and dynamic behaviour of elastic waveguides. Concepts of differential geometry and topology are put forward to provide a theoretical understanding of the geometric phase and its connection to the physical properties of the system. Then, the concept of geometric phase is applied to different types of elastic waveguides to explain how either topologically trivial or non-trivial behaviour can emerge based on the geometric features of the waveguide. This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 2)’. 

Glycosynthases are mutant glycosyl hydrolases that can synthesize glycosidic bonds between acceptor glycone/aglycone groups and activated donor sugars with suitable leaving groups (e.g., azido, fluoro). However, it has been challenging to rapidly detect glycosynthase reaction products involving azido sugars as donor sugars. This has limited our ability to apply rational engineering and directed evolution methods to rapidly screen for improved glycosynthases that are capable of synthesizing bespoke glycans. Here, we outline our recently developed screening methodologies for rapidly detecting glycosynthase activity using a model fucosynthase enzyme engineered to be active on fucosyl azide as donor sugar. We created a diverse library of fucosynthase mutants using semi-random and random error prone mutagenesis and then identified improved fucosynthase mutants with desired activity using two distinct screening methods developed by our group to detect glycosynthase activity (i.e., by detecting azide formed upon completion of fucosynthase reaction); (a) pCyn-GFP regulon method, and (b) Click chemistry method. Finally, we provide some proof-of-concept results illustrating the utility of both these screening methods to rapidly detect products of glycosynthase reactions involving azido sugars as donor groups. 

Background: Altered kinase localization is gaining appreciation as a mechanism of cardiovascular disease. Previous work suggests GSK-3β (glycogen synthase kinase 3β) localizes to and regulates contractile function of the myofilament. We aimed to discover GSK-3β’s in vivo role in regulating myofilament function, the mechanisms involved, and the translational relevance. Methods: Inducible cardiomyocyte-specific GSK-3β knockout mice and left ventricular myocardium from nonfailing and failing human hearts were studied. Results: Skinned cardiomyocytes from knockout mice failed to exhibit calcium sensitization with stretch indicating a loss of length-dependent activation (LDA), the mechanism underlying the Frank-Starling Law. Titin acts as a length sensor for LDA, and knockout mice had decreased titin stiffness compared with control mice, explaining the lack of LDA. Knockout mice exhibited no changes in titin isoforms, titin phosphorylation, or other thin filament phosphorylation sites known to affect passive tension or LDA. Mass spectrometry identified several z-disc proteins as myofilament phospho-substrates of GSK-3β. Agreeing with the localization of its targets, GSK-3β that is phosphorylated at Y216 binds to the z-disc. We showed pY216 was necessary and sufficient for z-disc binding using adenoviruses for wild-type, Y216F, and Y216E GSK-3β in neonatal rat ventricular cardiomyocytes. One of GSK-3β’s z-disc targets, abLIM-1 (actin-binding LIM protein 1), binds to the z-disc domains of titin that are important for maintaining passive tension. Genetic knockdown of abLIM-1 via siRNA in human engineered heart tissues resulted in enhancement of LDA, indicating abLIM-1 may act as a negative regulator that is modulated by GSK-3β. Last, GSK-3β myofilament localization was reduced in left ventricular myocardium from failing human hearts, which correlated with depressed LDA. Conclusions: We identified a novel mechanism by which GSK-3β localizes to the myofilament to modulate LDA. Importantly, z-disc GSK-3β levels were reduced in patients with heart failure, indicating z-disc localized GSK-3β is a possible therapeutic target to restore the Frank-Starling mechanism in patients with heart failure. 

We report supramolecular photocatalytic hydrogels, produced by the enzymatically driven self-assembly of low molecular weight gelators (LMWGs). These LMWG precursors are composed of the organic chromophore diketopyrrolopyrrole (DPP), which is bi-functionalized with a series of amino acid (Phe, Tyr, Leu) methyl esters. In situ enzymatic hydrolysis of these photoactive precursors results in supramolecular hydrogels that provide a high density of photocatalytic sites. Under visible light irradiation these hydrophobic fibers recruit the reaction substrates and also produce 1 O 2 , which is used here for the photooxidation of thioanisole (aromatic substrate) and cyclohexyl methyl sulfide (aliphatic substrate), with yields as high as 100% and without over-oxidation. Finally, we demonstrate that the nature of the amino acids in the LWMGs has a central role in dictating J-/H-/mixed state aggregates, gel properties, and, hence, the efficiency of chemoselective photooxidation of thioanisole and cyclohexyl methyl sulfide inside these hydrogels.