Duchenne muscular dystrophy (DMD) affects myofibers and muscle stem cells, causing progressive muscle degeneration and repair defects. It was unknown whether dystrophic myoblasts—the effector cells of muscle growth and regeneration—are affected. Using transcriptomic, genome-scale metabolic modelling and functional analyses, we demonstrate, for the first time, convergent abnormalities in primary mouse and human dystrophic myoblasts. In Dmd^mdx myoblasts lacking full-length dystrophin, the expression of 170 genes was significantly altered. Myod1 and key genes controlled by MyoD (Myog, Mymk, Mymx, epigenetic regulators, ECM interactors, calcium signalling and fibrosis genes) were significantly downregulated. Gene ontology analysis indicated enrichment in genes involved in muscle development and function. Functionally, we found increased myoblast proliferation, reduced chemotaxis and accelerated differentiation, which are all essential for myoregeneration. The defects were caused by the loss of expression of full-length dystrophin, as similar and not exacerbated alterations were observed in dystrophin-null Dmd^mdx-βgeo myoblasts. Corresponding abnormalities were identified in human DMD primary myoblasts and a dystrophic mouse muscle cell line, confirming the cross-species and cell-autonomous nature of these defects. The genome-scale metabolic analysis in human DMD myoblasts showed alterations in the rate of glycolysis/gluconeogenesis, leukotriene metabolism, and mitochondrial beta-oxidation of various fatty acids. These results reveal the disease continuum: DMD defects in satellite cells, the myoblast dysfunction affecting muscle regeneration, which is insufficient to counteract muscle loss due to myofiber instability. Contrary to the established belief, our data demonstrate that DMD abnormalities occur in myoblasts, making these cells a novel therapeutic target for the treatment of this lethal disease.

Marine biofouling imposes serious environmental and economic impacts on marine applications, especially in the shipping industry. To combat biofouling, protective coatings are applied on vessel hulls which are divided into two major groups: biocidal and non‐toxic fouling release. The current study aimed to explore the effect of coating type on microbial biofilm community profiles to better understand the differences between the communities developed on fouling control biocidal antifouling and biocidal‐free coatings. Biocidal (Intersmooth® 7460HS SPC), fouling release (Intersleek® 900), and inert surfaces were deployed in the marine environment for 4 months, and the biofilms that developed on these surfaces were investigated using Illumina NGS sequencing, targeting the prokaryotic 16S rRNA gene. The results confirmed differences in the community profiles between coating types. The biocidal coating supported communities dominated by Alphaproteobacteria (Loktanella, Sphingorhabdus, Erythrobacter) and Bacteroidetes (Gilvibacter), while other taxa, such as Portibacter and Sva0996 marine group, proliferated on the fouling‐release surface. Knowledge of these marine biofilm components on fouling control coatings will serve as a guide for future investigations of marine microfouling as well as informing the coatings industry of potential microbial targets for robust coating formulations.

The large-scale global use of plastics has led to one of the greatest environmental issues of the 21st century. The incredible durability of these polymers, whilst beneficial for a wide range of purposes, makes them hard to break down. True recycling of plastics is difficult and expensive, leading to accumulation in the environment as waste. Recently, a new field of research has developed, aiming to use natural biological processes to solve this man-made problem. Incredibly, some microorganisms are able to produce enzymes with the capacity to chemically break down plastic polymers into their monomeric building blocks. At an industrial scale, this process could allow for a circular recycling economy, whereby plastics are broken down, then built back up into novel consumer plastics. As well as providing a solution for the removal of plastics from the environment, this would also eliminate the need for the creation of virgin plastics. Analytical techniques, such as those allowing quantification of depolymerisation activity and enzyme characterization, have underpinned this field and created a strong foundation for this nascent inter-disciplinary field. Recent advances in cutting-edge ‘omics approaches such as DNA and RNA sequencing, combined with machine learning strategies, provide in-depth analysis of genomic systems involved in degradation. In particular, this can provide understanding of the specific protein sequence of the enzymes involved in the process, as well as insights into the functional and mechanistic role of the enzymes within these microorganisms, allowing for potential high-throughput discovery and subsequent exploitation of novel depolymerases. Together, these cross-disciplinary analytical techniques offer a complete pipeline for the identification, validation, and upscaling of potential enzymatic solutions for industrial deployment. In this review, we provide a summary of the research within the field to date, the analytical techniques most commonly applied for enzyme discovery and industrial upscaling, and provide recommendations for a standardised approach to allow research conducted in this field to be benchmarked to ensure focus is on the discovery and characterisation of industrially relevant enzymes.

The biomaterial with the highest known tensile strength is a unique composite of chitin and goethite (α-FeO(OH)) present in teeth from the Common Limpet (Patella vulgata). A biomimetic based on limpet tooth, with corresponding high-performance mechanical properties is highly desirable. Here we report on the replication of limpet tooth developmental processes ex vivo, where isolated limpet tissue and cells in culture generate new biomimetic structures. Transcriptomic analysis of each developmental stage of the radula, the organ from which limpet teeth originate, identifies sequential changes in expression of genes related to chitin and iron processing. We quantify iron and chitin metabolic processes in the radula and grow isolated radula cells in vitro. Bioinspired material can be developed with electrospun chitin mineralised by conditioned media from cultured radula cells. Our results inform molecular processes behind the generation of limpet tooth and establish a platform for development of a novel biomimetic with comparable properties.

Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment information) for 929 patient cases seen at a large UK hospital Trust between March 2020 and May 2021. We identified associations between acute physiological status and three measures of disease severity; admission to the intensive care unit (ICU), requirement for intubation, and mortality. Whilst the maximum National Early Warning Score (NEWS2) was moderately associated with severe COVID-19 (A = 0.48), the admission NEWS2 was only weakly associated (A = 0.17), suggesting it is ineffective as an early predictor of severity. Patient outcome was weakly associated with myriad factors linked to acute physiological status and human genetics, including age, sex and pre-existing conditions. Overall, we found no significant links between viral genomics and severe outcomes, but saw evidence that variant subtype may impact relative risk for certain sub-populations. Specific mutations of SARS-CoV-2 appear to have little impact on overall severity risk in these data, suggesting that emerging SARS-CoV-2 variants do not result in more severe patient outcomes. However, our results show that determining a causal relationship between mutations and severe COVID-19 in the viral genome is challenging. Whilst improved understanding of the evolution of SARS-CoV-2 has been achieved through genomics, few studies on how these evolutionary changes impact on clinical outcomes have been seen due to complexities associated with data linkage. By combining viral genomics with patient records in a large acute UK hospital, this study represents a significant resource for understanding risk factors associated with COVID-19 severity. However, further understanding will likely arise from studies of the role of host genetics on disease progression.

Background: Historically the main source of laboratoryXenopus laeviswas the environment. The increase in genetically altered animals and evolving governmental constraints around using wild-caught animals for research has led to the establishment of resource centres that supply animals and reagents worldwide, such as the EuropeanXenopusResource Centre. In the last decade, centres were encouraged to keep animals in a “low microbial load” or “clean” state, where embryos are surface sterilized before entering the housing system; instead of the conventional, “standard” conditions where frogs and embryos are kept without prior surface treatment. DespiteXenopus laevishaving been kept in captivity for almost a century, surprisingly little is known about the frogs as a holobiont and how changing the microbiome may affect resistance to disease. This study examines how the different treatment conditions, “clean” and “standard” husbandry in recirculating housing, affects the skin microbiome of tadpoles and female adults. This is particularly important when considering the potential for poor welfare caused by a change in husbandry method as animals move from resource centres to smaller research colonies.Results: We found strong evidence for developmental control of the surface microbiome onXenopus laevis; adults had extremely similar microbial communities independent of their housing, while both tadpole and environmental microbiome communities were less resilient and showed greater diversity.Conclusions: Our findings suggest that the adultXenopus laevismicrobiome is controlled and selected by the host. This indicates that the surface microbiome of adultXenopus laevisis stable and defined independently of the environment in which it is housed, suggesting that the use of clean husbandry conditions poses little risk to the skin microbiome when transferring adult frogs to research laboratories. This will have important implications for frog health applicable toXenopus laevisresearch centres throughout the world.