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Journal articleJiang Q, Otáhalová V, Burré V, et al., 2024,
Variable capacity polymer based energy harvesters with integrated macroporous elastomer springs
, Nano Energy, Vol: 124, ISSN: 2211-2855We introduce a manufacturing concept of variable capacity energy harvesters consisting of macroporous springs integrated within a conducting silicone rubber and dielectric. Printing and polymerising emulsion templates resulted in macroporous spring elements, which were coated with conducting silicone rubber to maintain the active contact surface. By increasing size and number of these springs, the capacitance change of the energy harvesters during compression and recovery increased from 0.4 nF/cm2 to 0.8 nF/cm2. During cyclic loading with 30 N at 2 Hz, the energy harvesters with macroporous springs delivered a power density of 0.58 µW/cm2 at a bias voltage of 50 V, which was 25 times higher than the control without springs. The energy harvesters provided a constant power output over three hours of cyclic loading (21,600 cycles), indicating their structural stability and the durability of the macroporous springs.
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Journal articleWisnom MR, Pimenta S, Shaffer MSP, et al., 2024,
High performance ductile and pseudo-ductile polymer matrix composites: a review
, Composites Part A: Applied Science and Manufacturing, Vol: 181, ISSN: 1359-835XThe ability of fibre reinforced composites to deform with a non-linear stress–strain response and gradual, rather than sudden, catastrophic failure is reviewed. The principal mechanisms by which this behaviour can be achieved are discussed, including ductile fibres, progressive fibre fracture and fragmentation, fibre reorientation, and slip between discontinuous elements. It is shown that all these mechanisms allow additional strain to be achieved, enabling a yield-like behaviour to be generated. In some cases, the response is ductile and in others pseudo-ductile. Mechanisms can also be combined, and composites which give significant pseudo-ductile strain can be produced. Notch sensitivity is reduced, and there is the prospect of increasing design strains whilst also improving damage tolerance. The change in stiffness or visual indications of damage can be exploited to give warning that strain limits have been exceeded. Load carrying capacity is still maintained, allowing continued operation until repairs can be made. Areas for further work are identified which can contribute to creating structures made from high performance ductile or pseudo-ductile composites that fail gradually.
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Journal articleChakraborty A, Alsharqi L, Kostrzewa M, et al., 2024,
Intact cell lipidomics using the Bruker MBT lipid Xtract assay allows the rapid detection of glycosyl-inositol-phospho-ceramides from Aspergillus fumigatus.
, Mol OmicsGlycosyl-inositol-phospho-ceramides (GIPCs) or glycosylphosphatidylinositol-anchored fungal polysaccharides are major lipids in plant and fungal plasma membranes and play an important role in stress adaption. However, their analysis remains challenging due to the multiple steps involved in their extraction and purification prior to mass spectrometry analysis. To address this challenge, we report here a novel simplified method to identify GIPCs from Aspergillus fumigatus using the new Bruker MBT lipid Xtract assay. A. fumigatus reference strains and clinical isolates were cultured, harvested, heat-inactivated and suspended in double-distilled water. A fraction of this fungal preparation was then dried in a microtube, mixed with an MBT lipid Xtract matrix (Bruker Daltonik, Germany) and loaded onto a MALDI target plate. Analysis was performed using a Bruker MALDI Biotyper Sirius system in the linear negative ion mode. Mass spectra were scanned from m/z 700 to m/z 2 000. MALDI-TOF MS analysis of cultured fungi showed a clear signature of GIPCs in Aspergillus fumigatus reference strains and clinical isolates. Here, we have demonstrated that routine MALDI-TOF in the linear negative ion mode combined with the MBT lipid Xtract is able to detect Aspergillus fumigatus GIPCs.
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Journal articleDelhaye G, van der Linde S, Bauman D, et al., 2024,
Ectomycorrhizal fungi are influenced by ecoregion boundaries across Europe
, Global Ecology and Biogeography, ISSN: 1466-822X<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>Ecoregions and the distance decay in community similarity are fundamental concepts in biogeography and conservation biology that are well supported across plants and animals, but not fungi. Here we test the relevance of these concepts for ectomycorrhizal (ECM) fungi in temperate and boreal regions.</jats:p></jats:sec><jats:sec><jats:title>Location</jats:title><jats:p>Europe.</jats:p></jats:sec><jats:sec><jats:title>Time Period</jats:title><jats:p>2008–2015.</jats:p></jats:sec><jats:sec><jats:title>Major Taxa Studied</jats:title><jats:p>Ectomycorrhizal fungi.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used a large dataset of ~24,000 ectomycorrhizas, assigned to 1350 operational taxonomic units, collected from 129 forest plots via a standardized protocol. We investigated the relevance of ecoregion delimitations for ECM fungi through complementary methodological approaches based on distance decay models, multivariate analyses and indicator species analyses. We then evaluated the effects of host tree and climate on the observed biogeographical distributions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Ecoregions predict large‐scale ECM fungal biodiversity patterns. This is partly explained by climate differences between ecoregions but independent from host tree distribution. Basidiomycetes in the orders Russulales and Atheliales and producing epigeous fruiting bodies, with potentially short‐distance dispersal, show the best agreement with ecoregion boundaries. Host tree distribution and fungal abundance (as opposed to presence/absence only) are important to uncover biogeographical patterns in mycorrhizas.</jats:p>&l
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Journal articleMcNally P, Singh A, McColley SA, et al., 2024,
Safety and efficacy of ivacaftor in infants aged 1 to less than 4 months with cystic fibrosis.
, J Cyst FibrosBACKGROUND: Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 to <4 months with CF. METHODS: In this phase 3, open-label study, infants 1 to <4 months with CF and an IVA-responsive CFTR variant received an initial low dose of IVA based on age and weight. Because IVA is a sensitive CYP3A substrate and CYP3A maturation is uncertain in infants, doses were adjusted at day 15 to better match median adult exposures based on individual PK measurements taken on day 4. Primary endpoints were safety and PK measurements. RESULTS: Seven infants (residual function CFTR variants [n=5]; minimal function CFTR variants [n=2]) received ≥1 dose of IVA. Six infants had doses adjusted at day 15 and one infant did not require dose adjustment; subsequent PK analyses showed mean trough concentrations for IVA and metabolites were within range of prior clinical experience. Four infants (57.1%) had adverse events (AEs); no serious AEs were noted. One infant discontinued study drug due to a non-serious AE of elevated alanine aminotransferase >8x the upper limit of normal. Mean sweat chloride concentration decreased (-40.3 mmol/L [SD: 29.2]) through week 24. Improvements in biomarkers of pancreatic function and intestinal inflammation, as well as growth parameters, were observed. CONCLUSIONS: In this small, open-label study, IVA dosing in infants achieved exposures previously shown to be safe and efficacious. Because PK was predictable, a dosing regimen based on age and weight is proposed. IVA was generally safe and well tolerated, and led to improvements in CFTR function, markers of pancreatic function and intestinal inflammation, and growth parameters, supporting use in infants as young as 1 month of age.
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Journal articleWu Y, Li Y, Liu Y, et al., 2024,
Multiplexed in-situ mutagenesis driven by a dCas12a-based dual-function base editor.
, Nucleic Acids ResMutagenesis driving genetic diversity is vital for understanding and engineering biological systems. However, the lack of effective methods to generate in-situ mutagenesis in multiple genomic loci combinatorially limits the study of complex biological functions. Here, we design and construct MultiduBE, a dCas12a-based multiplexed dual-function base editor, in an all-in-one plasmid for performing combinatorial in-situ mutagenesis. Two synthetic effectors, duBE-1a and duBE-2b, are created by amalgamating the functionalities of cytosine deaminase (from hAPOBEC3A or hAID*Δ ), adenine deaminase (from TadA9), and crRNA array processing (from dCas12a). Furthermore, introducing the synthetic separator Sp4 minimizes interference in the crRNA array, thereby facilitating multiplexed in-situ mutagenesis in both Escherichia coli and Bacillus subtilis. Guided by the corresponding crRNA arrays, MultiduBE is successfully employed for cell physiology reprogramming and metabolic regulation. A novel mutation conferring streptomycin resistance has been identified in B. subtilis and incorporated into the mutant strains with multiple antibiotic resistance. Moreover, surfactin and riboflavin titers of the combinatorially mutant strains improved by 42% and 15-fold, respectively, compared with the control strains with single gene mutation. Overall, MultiduBE provides a convenient and efficient way to perform multiplexed in-situ mutagenesis.
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Journal articleWalker K, Li IS, Lee K, et al., 2024,
Self-pigmenting textiles grown from cellulose-producing bacteria with engineered tyrosinase expression
, Nature Biotechnology, ISSN: 1087-0156Environmental concerns are driving interest in postpetroleum synthetic textiles produced from microbial and fungal sources. Bacterial cellulose (BC) is a promising sustainable leather alternative, on account of its material properties, low infrastructure needs and biodegradability. However, for alternative textiles like BC to be fully sustainable, alternative ways to dye textiles need to be developed alongside alternative production methods. To address this, we genetically engineer Komagataeibacter rhaeticus to create a bacterial strain that grows self-pigmenting BC. Melanin biosynthesis in the bacteria from recombinant tyrosinase expression achieves dark black coloration robust to material use. Melanated BC production can be scaled up for the construction of prototype fashion products, and we illustrate the potential of combining engineered self-pigmentation with tools from synthetic biology, through the optogenetic patterning of gene expression in cellulose-producing bacteria. With this study, we demonstrate that combining genetic engineering with current and future methods of textile biofabrication has the potential to create a new class of textiles.
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Journal articleWu Z, Spencer LG, Banya W, et al., 2024,
Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial
, The Lancet Respiratory Medicine, Vol: 12, Pages: 273-280, ISSN: 2213-2600BackgroundIdiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis.MethodsThe PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40–90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed.FindingsBetween Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82%
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Journal articleJones MP, Jiang Q, Mautner A, et al., 2024,
Fungal Carbon: A Cost-Effective Tunable Network Template for Creating Supercapacitors.
, Glob Chall, Vol: 8Carbons form critical components in biogas purification and energy storage systems and are used to modify polymer matrices. The environmental impact of producing carbons has driven research interest in biomass-derived carbons, although these have yield, processing, and resource competition limitations. Naturally formed fungal filaments are investigated, which are abundantly available as food- and biotechnology-industry by-products and wastes as cost-effective and sustainable templates for carbon networks. Pyrolyzed Agaricus bisporus and Pleurotus eryngii filament networks are mesoporous and microscale with a size regime close to carbon fibers. Their BET surface areas of ≈282 m2 g-1 and ≈60 m2 g-1, respectively, greatly exceed values associated with carbon fibers and non-activated pyrolyzed bacterial cellulose and approximately on par with values for carbon black and CNTs in addition to pyrolyzed pinewood, rice husk, corn stover or olive mill waste. They also exhibit greater specific capacitance than both non-activated and activated pyrolyzed bacterial cellulose in addition to YP-50F (coconut shell based) commercial carbons. The high surface area and specific capacitance of fungal carbon coupled with the potential to tune these properties through species- and growth-environment-associated differences in network and filament morphology and inclusion of inorganic material through biomineralization makes them potentially useful in creating supercapacitors.
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Journal articleWebster VL, Hemmings S, Pérez M, et al., 2024,
Revealing the genome of the microsporidian Vairimorpha bombi, a potential driver of bumble bee declines in North America
, G3: Genes, Genomes, Genetics, Vol: 14, ISSN: 2160-1836Pollinators are vital for food security and the maintenance of terrestrial ecosystems. Bumblebees are important pollinators across northern temperate, arctic, and alpine ecosystems, yet are in decline across the globe. Vairimorpha bombi is a parasite belonging to the fungal class Microsporidia that has been implicated in rapid declines of bumblebees in North America, where it may be an emerging infectious disease. To investigate the evolutionary basis of pathogenicity of V. bombi, we sequenced and assembled its genome using Oxford Nanopore and Illumina technologies and performed phylogenetic and genomic evolutionary analyses. The genome assembly for V. bombi is 4.73 Mb, from which we predicted 1,870 protein coding genes and 179 tRNA genes. The genome assembly has low repetitive content and low GC content. V. bombi's genome assembly is the smallest of the Vairimorpha and closely related Nosema genera, but larger than those found in the Encephalitozoon and Ordospora sister clades. Orthology and phylogenetic analysis revealed 18 core conserved single-copy microsporidian genes including the Histone acetyltransferase (HAT) GCN5. Surprisingly, V. bombi was unique to the microsporidia in not encoding the 2nd predicted HAT ESA1. The V. bombi genome assembly annotation included 265 unique genes (i.e., not predicted in other microsporidia genome assemblies), 20% of which encode a secretion signal, which is a significant enrichment. Intriguingly, of the 36 microsporidian genomes we analysed, 26 also had a significant enrichment of secreted signals encoded by unique genes, ranging from 6% to 71% of those predicted genes. These results suggest that microsporidia are under selection to generate and purge diverse and unique genes encoding secreted proteins, potentially contributing to or facilitating infection of their diverse hosts. Furthermore, V. bombi has 5/7 conserved Spore Wall Proteins (SWPs) with its closest relative V. ceranae (that primarily infects honeybees), while als
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