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1. Spatiotemporal development of coexisting wave domains of Rho activity in the cell cortex

   https://doi.org/10.1038/s41598-021-99029-x  

   Hladyshau, Siarhei; Kho, Mary; Nie, Shuyi; Tsygankov, Denis (December 2021, Scientific Reports)

   Abstract The Rho family GTPases are molecular switches that regulate cytoskeletal dynamics and cell movement through a complex spatiotemporal organization of their activity. In Patiria miniata (starfish) oocytes under in vitro experimental conditions (with overexpressed Ect2, induced expression of Δ90 cyclin B, and roscovitine treatment), such activity generates multiple co-existing regions of coherent propagation of actin waves. Here we use computational modeling to investigate the development and properties of such wave domains. The model reveals that the formation of wave domains requires a balance between the activation and inhibition in the Rho signaling motif. Intriguingly, the development of the wave domains is preceded by a stage of low-activity quasi-static patterns, which may not be readily observed in experiments. Spatiotemporal patterns of this stage and the different paths of their destabilization define the behavior of the system in the later high-activity (observable) stage. Accounting for a strong intrinsic noise allowed us to achieve good quantitative agreement between simulated dynamics in different parameter regimes of the model and different wave dynamics in Patiria miniata and wild type Xenopus laevis (frog) data. For quantitative comparison of simulated and experimental results, we developed an automated method of wave domain detection, which revealed a sharp reversal in the process of pattern formation in starfish oocytes. Overall, our findings provide an insight into spatiotemporal regulation of complex and diverse but still computationally reproducible cell-level actin dynamics. 

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2. Catalytic MXCeO2 for enzyme based electrochemical biosensors: Fabrication, characterization and application towards a wearable sweat biosensor

   https://doi.org/10.1016/j.bios.2023.115975  

   Khan, Reem; Andreescu, Silvana (March 2024, Biosensors and Bioelectronics)

   Two-dimensional (2D) layered materials that integrate metallic conductivity, catalytic activity and the ability to stabilize biological receptors provide unique capabilities for designing electrochemical biosensors for large-scale detection and diagnostic applications. Herein, we report a multifunctional MXene-based 2D nanostructure decorated with enzyme mimetic cerium oxide nanoparticle (MXCeO2) as a novel platform and catalytic amplifier for electrochemical biosensors, specifically targeting the detection of oxidase enzyme substrates. We demonstrate enhanced catalytic efficiency of the MXCeO2 for the reduction of hydrogen peroxide (H2O2) and its ability to immobilize oxidase enzymes, such as glucose oxidase, lactate oxidase and xanthine oxidase. The designed biosensors exhibit high selectivity, stability, and sensitivity, achieving detection limits of 0.8 μM H2O2, 0.49 μM glucose, 3.6 μM lactate and 1.7 μM hypoxanthine, when the MXCeO2 and their respective enzymes were used. The MXCeO2 was successfully incorporated into a wearable fabric demonstrating high sensitivity for lactate measurements in sweat. The unique combination of MXenes with CeO2 offers excellent conductivity, catalytic efficiency and enhanced enzyme loading, demonstrating potential of the MXCeO2 as a catalytically active material to boost efficiency of oxidase enzyme reactions. This design can be used as a general platform for increasing the sensitivity of enzyme based biosensors and advance the development of electrochemical biosensors for a variety of applications. 

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3. Electrochemical transformations catalyzed by cytochrome P450s and peroxidases

   https://doi.org/10.1039/D3CS00461A  

   Kumar, Neeraj; He, Jie; Rusling, James F. (July 2023, Chemical Society Reviews)

   Cytochrome P450s (Cyt P450s) and peroxidases are enzymes featuring iron heme cofactors that have wide applicability as biocatalysts in chemical syntheses. Cyt P450s are a family of monooxygenases that oxidize fatty acids, steroids, and xenobiotics, synthesize hormones, and convert drugs and other chemicals to metabolites. Peroxidases are involved in breaking down hydrogen peroxide and can oxidize organic compounds during this process. Both heme-containing enzymes utilize active FeIV[double bond, length as m-dash]O intermediates to oxidize reactants. By incorporating these enzymes in stable thin films on electrodes, Cyt P450s and peroxidases can accept electrons from an electrode, albeit by different mechanisms, and catalyze organic transformations in a feasible and cost-effective way. This is an advantageous approach, often called bioelectrocatalysis, compared to their biological pathways in solution that require expensive biochemical reductants such as NADPH or additional enzymes to recycle NADPH for Cyt P450s. Bioelectrocatalysis also serves as an ex situ platform to investigate metabolism of drugs and bio-relevant chemicals. In this paper we review biocatalytic electrochemical reactions using Cyt P450s including C–H activation, S-oxidation, epoxidation, N-hydroxylation, and oxidative N-, and O-dealkylation; as well as reactions catalyzed by peroxidases including synthetically important oxidations of organic compounds. Design aspects of these bioelectrocatalytic reactions are presented and discussed, including enzyme film formation on electrodes, temperature, pH, solvents, and activation of the enzymes. Finally, we discuss challenges and future perspective of these two important bioelectrocatalytic systems. 

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4. Honey Bees ( Apis mellifera Hymenoptera: Apidae) Preferentially Avoid Sugar Solutions Supplemented with Field-Relevant Concentrations of Hydrogen Peroxide Despite High Tolerance Limits

   https://doi.org/10.1093/jisesa/ieab102  

   Bartlett, Lewis J; Martinez-Mejia, Carlos; Delaplane, Keith S (January 2022, Journal of Insect Science)

   Brunet, Johanne (Ed.)

   Abstract Honey bees (Apis mellifera L. Hymeoptera: Apidae) use hydrogen peroxide (synthesized by excreted glucose oxidase) as an important component of social immunity. However, both tolerance of hydrogen peroxide and the production of glucose oxidase in honey is costly. Hydrogen peroxide may also be encountered by honey bees at high concentrations in nectar while foraging, however despite its presence both in their foraged and stored foods, it is unclear if and how bees monitor concentrations of, and their behavioral responses to, hydrogen peroxide. The costs of glucose oxidase production and the presence of hydrogen peroxide in both nectar and honey suggest hypotheses that honey bees preferentially forage on hydrogen peroxide supplemented feed syrups at certain concentrations, and avoid feed syrups supplemented with hydrogen peroxide at concentrations above some tolerance threshold. We test these hypotheses and find that, counter to expectation, honey bees avoid glucose solutions supplemented with field-relevant hydrogen peroxide concentrations and either avoid or don’t differentiate supplemented sucrose solutions when given choice assays. This is despite honey bees showing high tolerance for hydrogen peroxide in feed solutions, with no elevated mortality until concentrations of hydrogen peroxide exceed 1% (v/v) in solution, with survival apparent even at concentrations up to 10%. The behavioral interaction of honey bees with hydrogen peroxide during both within-colony synthesis in honey and when foraging on nectar therefore likely relies on interactions with other indicator molecules, and maybe constrained evolutionarily in its plasticity, representing a constitutive immune mechanism. 

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5. Neuronal temperature perception induces specific defenses that enable C. elegans to cope with the enhanced reactivity of hydrogen peroxide at high temperature

   https://doi.org/10.7554/eLife.78941  

   Servello, Francesco A; Fernandes, Rute; Eder, Matthias; Harris, Nathan; Martin, Olivier MF; Oswal, Natasha; Lindberg, Anders; Derosiers, Nohelly; Sengupta, Piali; Stroustrup, Nicholas; et al (October 2022, eLife)

   The Earth’s environment is full of reactive chemicals that can cause harm to organisms. One of the most common is hydrogen peroxide, which is produced by several bacteria in concentrations high enough to kill small animals, such as the roundworm Caenorhabditis elegans . Forced to live in close proximity to such perils, C. elegans have evolved defenses to ensure their survival, such as producing enzymes that can break down hydrogen peroxide. However, this battle is compounded by other factors. For instance, rising temperatures can increase the rate at which the hydrogen peroxide produced by bacteria reacts with the molecules and proteins of C. elegans . In 2020, a group of researchers found that roundworms sense these temperature changes through special cells called sensory neurons and use this information to control the generation of enzymes that break down hydrogen peroxide. This suggests that C. elegans may pre-emptively prepare their defenses against hydrogen peroxide in response to higher temperatures so they are better equipped to shield themselves from this harmful chemical. To test this theory, Servello et al. – including some of the authors involved in the 2020 study – exposed C. elegans to a species of bacteria that produces hydrogen peroxide. This revealed that the roundworms were better at dealing with the threat of hydrogen peroxide when growing in warmer temperatures. Experiments done in C. elegans lacking a class of sensory cells, the AFD neurons, showed that these neurons increased the roundworms’ resistance to the chemical when temperatures increase. They do this by repressing the activity of INS-39, a hormone that stops C. elegans from switching on their defense mechanism against peroxides. This is the first example of a multicellular organism preparing its defenses to a chemical after sensing something (such as temperature) that enhances its reactivity. It is possible that other animals may also use this ‘enhancer sensing' strategy to anticipate and shield themselves from hydrogen peroxide and potentially other external threats. 

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