Design of oscillatory dynamics in numerical simulations of compartment-based enzyme systems.

Enzymatic reactions that yield non-neutral products are known to involve feedback due to the bell-shaped pH-rate curve of the enzyme. Compartmentalizing the reaction has been shown to lead to transport-driven oscillations in theory; however, there have been few reproducible experimental examples. Our objective was to determine how the conditions could be optimized to achieve pH oscillations.

A microfluidic double emulsion platform for spatiotemporal control of pH and particle synthesis.

The temporal control of pH in microreactors such as emulsion droplets plays a vital role in applications including biomineralisation and microparticle synthesis. Typically, pH changes are achieved either by passive diffusion of species into a droplet or by acid/base producing reactions. Here, we exploit an enzyme reaction combined with the properties of a water-oil-water (W/O/W) double emulsion to control the pH-time profile in the droplets.

Changing the paradigm in modelling the Bray-Liebhafsky oscillatory chemical reaction.

The Bray-Liebhafsky (BL) reaction is one of the simplest chemical oscillators consisting initially of only three components. Despite this, its mechanism is unknown for more than 100 years due to the absence of selective, sensitive, and fast experimental techniques for following all of the involved intermediates. The modeling of the BL mechanism assumes presumably mass action kinetics "adjustable" to oscillatory solutions by the application of mathematical stability analysis and treating the system as homogeneous.

Influence of Oxygen on Chemoconvective Patterns in the Iodine Clock Reaction.

There is increasing interest in using chemical clock reactions to drive material formation; however, these reactions are often subject to chemoconvective effects, and control of such systems remains challenging. Here, we show how the transfer of oxygen at the air-water interface plays a crucial role in the spatiotemporal behavior of the iodine clock reaction with sulfite. A kinetic model was developed to demonstrate how the reaction of oxygen with sulfite can control a switch from a low-iodine to high-iodine state under well-stirred conditions and drive the formation of transient iodine gradients in unstirred solutions.

A Novel High-Throughput Ex Vivo Ovine Skin Wound Model for Testing Emerging Antibiotics.

The development of antimicrobials is an expensive process with increasingly low success rates, which makes further investment in antimicrobial discovery research less attractive. Antimicrobial drug discovery and subsequent commercialization can be made more lucrative if a fail-fast-and-fail-cheap approach can be implemented within the lead optimization stages where researchers have greater control over drug design and formulation. In this article, the setup of an ex vivo ovine wounded skin model infected with Staphylococcus aureus is described, which is simple, cost-effective, high throughput, and reproducible.

Coupling between nucleation and chemical reactions and its importance in understanding the oxidation of iodine by hydrogen peroxide.

We have investigated the reaction of iodine with hydrogen peroxide coupled to gas nucleation. A step-like increase in the nucleation rate with increasing amounts of dissolved oxygen can act as a trigger for the formation of highly reactive components and complete oxidation of iodine to iodate despite the large thermodynamic barrier for the whole process. Energetic coupling of nucleation with chemical reactions is based on local redistribution of energy by collapsing unstable nuclei.

Collective Behavior of Urease pH Clocks in Nano- and Microvesicles Controlled by Fast Ammonia Transport.

The transmission of chemical signals via an extracellular solution plays a vital role in collective behavior in cellular biological systems and may be exploited in applications of lipid vesicles such as drug delivery. Here, we investigated chemical communication in synthetic micro- and nanovesicles containing urease in a solution of urea and acid. We combined experiments with simulations to demonstrate that the fast transport of ammonia to the external solution governs the pH-time profile and synchronizes the timing of the pH clock reaction in a heterogeneous population of vesicles.

Reaction-diffusion hydrogels from urease enzyme particles for patterned coatings.

The reaction and diffusion of small molecules is used to initiate the formation of protective polymeric layers, or biofilms, that attach cells to surfaces. Here, inspired by biofilm formation, we present a general method for the growth of hydrogels from urease enzyme-particles by combining production of ammonia with a pH-regulated polymerization reaction in solution. We show through experiments and simulations how the propagating basic front and thiol-acrylate polymerization were continuously maintained by the localized urease reaction in the presence of urea, resulting in hydrogel layers around the enzyme particles at surfaces, interfaces or in motion.

Moving Pharmacogenetics Into Practice: It's All About the Evidence!

The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is highly debated. Therefore, the purpose of this review is to summarize different perspectives on the evidence required for the clinical implementation of pharmacogenetics.

Stop flailing: The impact of bicortically displaced rib fractures on pulmonary outcomes in patients with chest trauma - an American Association for the Surgery of Trauma multi-institutional study.

Background: Current evaluation of rib fractures focuses almost exclusively on flail chest with little attention on bicortically displaced fractures. Chest trauma that is severe enough to cause fractures leads to worse outcomes. An association between bicortically displaced rib fractures and pulmonary outcomes would potentially change patient care in the setting of trauma.

Periodic Nucleation of Calcium Phosphate in a Stirred Biocatalytic Reaction.

Highly ordered superstructures composed of inorganic nanoparticles appear in natural and synthetic systems, however the mechanisms of non-equilibrium self-organization that may be involved are still poorly understood. Herein, we performed a kinetic investigation of the precipitation of calcium phosphate using a process widely found in microorganisms: the hydrolysis of urea by enzyme urease. With high initial ratio of calcium ion to phosphate, periodic precipitation was obtained accompanied by pH oscillations in a well-stirred, closed reactor.

Correction: Common-variant associations with fragile X syndrome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Modelling Bacteria-Inspired Dynamics with Networks of Interacting Chemicals.

One approach to understanding how life-like properties emerge involves building synthetic cellular systems that mimic certain dynamical features of living cells such as bacteria. Here, we developed a model of a reaction network in a cellular system inspired by the ability of bacteria to form a biofilm in response to increasing cell density. Our aim was to determine the role of chemical feedback in the dynamics.

Influence of reaction-induced convection on quorum sensing in enzyme-loaded agarose beads.

In theory, groups of enzyme-loaded particles producing an acid or base may show complex behavior including dynamical quorum sensing, the appearance of synchronized oscillations above a critical number or density of particles. Here, experiments were performed with the enzyme urease loaded into mm-sized agarose beads and placed in a solution of urea, resulting in an increase in pH. This behavior was found to be dependent upon the number of beads present in the array; however, reaction-induced convection occurred and plumes of high pH developed that extended to the walls of the reactor.

Venous thromboembolism laboratory testing (factor V Leiden and factor II c.*97G>A), 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Factor V Leiden and factor II c.*97G>A (formerly referred to as prothrombin 20210G>A) are the two most common genetic variants associated with venous thromboembolism (VTE). Testing for these variants is one of the most common referrals in clinical genetics laboratories.

Towards feedback-controlled nanomedicines for smart, adaptive delivery.

The timing and rate of release of pharmaceuticals from advanced drug delivery systems is an important property that has received considerable attention in the scientific literature. Broadly, these mostly fall into two classes: controlled release with a prolonged release rate or triggered release where the drug is rapidly released in response to an environmental stimulus. This review aims to highlight the potential for developing adaptive release systems that more subtlety modulate the drug release profile through continuous communication with its environment facilitated through feedback control.

Switches induced by quorum sensing in a model of enzyme-loaded microparticles.

Quorum sensing refers to the ability of bacteria and other single-celled organisms to respond to changes in cell density or number with population-wide changes in behaviour. Here, simulations were performed to investigate quorum sensing in groups of diffusively coupled enzyme microparticles using a well-characterized autocatalytic reaction which raises the pH of the medium: hydrolysis of urea by urease. The enzyme urease is found in both plants and microorganisms, and has been widely exploited in engineering processes.