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Journal articleWagner M, Biegler V, Wurm S, et al., 2025,
Pulp fibre foams: Morphology and mechanical performance
, Composites Part A: Applied Science and Manufacturing, Vol: 188, ISSN: 1359-835XCellulose (pulp) fibre foams serve as bio-based alternative to fossil-based cellular lightweight materials. The mechanical properties of cellulose fibre foams are inferior compared with traditional polymer foams and available information is often limited to compression properties. We present a comprehensive analysis of cellulose fibre foams with densities ranging from 60 to 130 kg/m3, examining their compression, tensile, flexural, and shear properties. Key findings include a high mean zenithal fibre angle which decreases with increasing density, as well as a high strain rate amplification (SRA) in compressive strength, which also decreases with increasing density. With respect to formulation, the addition of carboxymethyl cellulose (CMC) enhanced fibre dispersion, bubble homogeneity of the wet foam, and dimensional stability of the end-product. These results provide a foundation for numerical models and advance the understanding of cellulose pulp fibre foams, highlighting their potential for certain applications.
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Journal articleOrzan E, Barrio A, Biegler V, et al., 2025,
Foaming and cross-linking of cellulose fibers using phytic acid.
, Carbohydr Polym, Vol: 347Bio-based compounds have become the focus in the development of next-generation materials. The polyphosphated structure and availability of phytic acid has sparked an interest to understand its properties and apply it to making fire-retardant fabrics. However, its degradative effect on natural fibers sets limitations to its potential uses. In this study, we unveiled a new dimension to explore with phytic acid: cellulose fiber foams. Phytic acid enabled synergistic foaming with carboxymethyl cellulose albeit causing issues in long-term wet foam stability. Adding cellulose fibers to this mixture and drying at 160 °C produced solid foams with increased compressive strength and stiffness; comparable to foams cross-linked with the commonly used citric acid. The reduced contact area in low-density fiber networks allowed the cross-linking between phytic acid and the fiber network to mitigate structural weakening due to fiber degradation. Imaging also revealed the formation of a film encompassing fiber bonds; attributed to the strong interaction between phytic acid and carboxymethyl cellulose. Furthermore, phytic acid imparted self-extinguishing fire-retardant properties to the cellulose fiber foams measured using thermogravimetric analysis and cone calorimetry. This work showcases a simple new application for phytic acid without the use of catalysts or solvents. It serves to encourage further development of green practices to continuously challenge the industrial landscape.
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Journal articleBottery MJ, van Rhijn N, Chown H, et al., 2024,
Elevated mutation rates in multi-azole resistant Aspergillus fumigatus drive rapid evolution of antifungal resistance.
, Nat Commun, Vol: 15The environmental use of azole fungicides has led to selective sweeps across multiple loci in the Aspergillus fumigatus genome causing the rapid global expansion of a genetically distinct cluster of resistant genotypes. Isolates within this cluster are also more likely to be resistant to agricultural antifungals with unrelated modes of action. Here we show that this cluster is not only multi-azole resistant but has increased propensity to develop resistance to next generation antifungals because of variants in the DNA mismatch repair system. A variant in msh6-G233A is found almost exclusively within azole resistant isolates harbouring the canonical cyp51A azole resistance allelic variant TR34/L98H. Naturally occurring isolates with this msh6 variant display up to 5-times higher rate of mutation, leading to an increased likelihood of evolving resistance to other antifungals. Furthermore, unlike hypermutator strains, the G233A variant conveys no measurable fitness cost and has become globally distributed. Our findings further suggest that resistance to next-generation antifungals is more likely to emerge within organisms that are already multi-azole resistant due to close linkage between TR34/L98H and msh6-G233A, posing a major problem due to the prospect of dual use of novel antifungals in clinical and agricultural settings.
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Journal articleDavies JC, Polineni D, Boyd AC, et al., 2024,
Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-in-Human Trial.
, Am J Respir Crit Care Med, Vol: 210, Pages: 1398-1408Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Although CF is a multiorgan disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of CFTR mutations on CFTR function has allowed for the development of CFTR modulator therapies. Despite the remarkable impact that these therapies have had, there remains a significant proportion of people with CF (estimated at 10-15% of the global CF population) who are genetically ineligible for, or intolerant of, current CFTR-targeting therapies and whose therapeutic needs remain unmet. Inhaled genetic therapies offer the prospect of addressing the unmet pulmonary treatment need in people with CF, with several approaches, including gene addition therapy (the focus of this review), RNA-based therapies, antisense oligonucleotides, and gene editing, being explored. Various nonviral and viral vectors have been investigated for CF gene addition therapy for mutation-agnostic restoration of CFTR function in the lungs. Lentiviral vectors offer the prospect of highly efficient and long-lasting gene expression, and the potential to be safely and, in contrast to other commonly used viral vectors, effectively redosed. A third-generation lentiviral vector pseudotyped with Sendai virus F and HN envelope proteins (rSIV.F/HN) has been developed for the treatment of CF. Promising preclinical results support the progression of this vector carrying a full-length CFTR transgene (BI 3720931) into a first-in-human clinical trial expected to begin in 2024.
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Journal articleMonteirinho Leitao RA, Leitao R, Wan IU, et al., 2024,
Detection of fungal sequences in human brain: rDNA locus amplification and deep sequencing
, Scientific Reports, ISSN: 2045-2322The aetiology of Alzheimer’s disease (AD) and Parkinson’s disease (PD) are unknown and tend to manifest at a late stage in life; eventhough these neurodegenerative diseases are caused by different affected proteins, they are both characterized by neuroinflammation.Links between bacterial and viral infection and AD/PD has been suggested in several studies, however, few have attempted to establisha link between fungal infection and AD/PD. In this study we adopted a nanopore-based sequencing approach to characterise thepresence or absence of fungal genera in both human brain tissue and cerebrospinal fluid (CSF). We observed the presence of smallfungal burden DNA in two AD brains and a control case (extensive amyloid angiopathy). This approach would be well-placed toinvestigate potential links between microbial infection and neurodegenerative disease.
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Journal articleRueda-Maíllo F, Garrido-Jurado I, Kotta-Loizou I, et al., 2024,
A mycoviral infection drives virulence and ecological fitness of the entomopathogenic fungus Beauveria bassiana.
, J Invertebr PatholEntomopathogenic ascomycetes are important natural regulators of insect pest populations and an increasingly adopted microbial control option. Fungal virulence in entomopathogenic ascomycetes can be modified by mycoviruses, viruses that infect fungi, whereas the possible role of these viruses on the physical and biochemical properties of the virus-containing fungal strains and on their ecological fitness has remained largely unexplored. Here, utilizing a Beauveria bassiana strain naturally infected with two mycoviruses, Beauveria bassiana partitivirus 2 (BbPV-2) and Beauveria bassiana polymycovirus 1 (BbPmV-1), we found that the mycovirus-containing strain is hypervirulent towards the experimental insect Galleria mellonella and shows major physical and biochemical changes in spore size, isoelectric point, and Pr1 activity, but even more impactful, the mycoviral infection confers a significant environmental- abiotic and biotic stress tolerance to the fungus. Hence, mycovirus infection expanded the temperature range for fungal growth and germination, and improved tolerance to osmotic stress, water stress, and UV-B radiation. Similarly, the antagonistic activity of the mycovirus-containing strain against Trichoderma harzianum was increased as compared to the mycovirus-free one. Taken together, these data suggest for the first time a mycovirus related adaptation of key traits indicators of environmental competence of a beneficial fungus, rendering these mycoviruses as potent tools for entomopathogenic fungal strain selection and development as mycoinsecticides.
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Journal articleIvan FX, Tiew PY, Jaggi TK, et al., 2024,
Sputum metagenomics reveals a multidrug resistant Pseudomonas-dominant severe asthma phenotype in an Asian population.
, RespirologyBACKGROUND AND OBJECTIVE: While the lung microbiome in severe asthma has been studied, work has employed targeted amplicon-based sequencing approaches without functional assessment with none focused on multi-ethnic Asian populations. Here we investigate the clinical relevance of microbial phenotypes of severe asthma in Asians using metagenomics. METHODS: Prospective assessment of clinical, radiological, and immunological measures were performed in a multi-ethnic Asian severe asthma cohort (N = 70) recruited across two centres in Singapore. Sputum was subjected to shotgun metagenomic sequencing and patients followed up for a 2-year period. Metagenomic assessment of sputum microbiomes, resistomes and virulomes were related to clinical outcomes. RESULTS: The lung microbiome in a multi-ethnic Asian cohort with severe asthma demonstrates an increased abundance of Pseudomonas species. Unsupervised clustering of sputum metagenomes identified two patient clusters: C1 (n = 52) characterized by upper airway commensals and C2 (n = 18) dominated by established respiratory pathogens including M. catarrhalis, S. aureus and most significantly P. aeruginosa. C2 patients demonstrated a significantly increased exacerbation frequency on 2-year follow up and an antimicrobial resistome characterized by multidrug resistance. Virulomes appear indistinguishable between severe asthmatics with or without co-existing bronchiectasis, and C2 patients exhibit increased gene expression related to biofilm formation, effector delivery systems and microbial motility. Independent comparison of the C2 cluster to a non-asthmatic bronchiectasis cohort demonstrates analogous airway microbial virulence patterns. CONCLUSION: Sputum metagenomics demonstrates a multidrug-resistant Pseudomonas-dominant severe asthma phenotype in Asians, characterized by poor clinical outcome including increased exacerbations which is independent of co-existing bronchiectasis.
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Journal articleBiegler V, Verdross P, Woodward RT, et al., 2024,
Cellulose fibre foam templated porous epoxy composites: Wetting matters
, Composites Part A: Applied Science and Manufacturing, Vol: 187, ISSN: 1359-835XCellulose foams were used to produce porous epoxy-composites. The influence of fibre wetting by the resins on foam morphology and resulting compression properties was investigated. Impregnated foam morphology determined the composite structures and their mechanical properties. Fibre preforms of various densities (40–80 kg·m−3) were prepared by frothing surfactant stabilised fibre suspensions. The preforms, exhibiting compressive strengths of 0.02 MPa, were impregnated with three different resins (a lignin-based resin BLER/MA, and two commercial formulations, A/A and A/XB). Depending on the formation of closed- or open-cell structures in the cured foam composites, compressive strengths of up to 2 MPa (BLER/MA), 33 MPa (A/A), or 23 MPa (A/XB), and compressive moduli of up to 47 MPa (BLER/MA), 468 MPa (A/A), or 379 MPa (A/XB) were obtained. The surface area, fibre coverage homogeneity, and composite morphology were investigated in relation to wetting. A tool kit for fibre foam templated porous composite design is provided.
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Journal articleWoubshete M, Chan LI, Diallinas G, et al., 2024,
The dimer of human SVCT1 is key for transport function.
, Biochim Biophys Acta Biomembr, Vol: 1866Humans and other primates lack the ability to synthesize the essential nutrient, Vitamin C, which is derived exclusively from the diet. Crucial for effective vitamin C uptake are the Na+ dependent Vitamin C transporters, SVCT1 and SVCT2, members of the nucleobase ascorbate transporter (NAT) family. SVCT1 and 2 actively transport the reduced form of Vitamin C, ascorbic acid, into key tissues. The recent structure of the mouse SVCT1 revealed the molecular basis of substrate binding and that, like the other structurally characterised members of the NAT family, it exists as a closely associated dimer. SVCT1 is likely to function via the elevator mechanism with the core domain of each protomer able to bind substrate and move through the membrane carrying the substrate across the membrane. Here we explored the function of a range of variants of the human SVCT1, revealing a range of residues involved in substrate selection and binding, and confirming the importance of the C-terminus in membrane localisation. Furthermore, using a dominant negative mutant we show that the dimer is essential for transport function, as previously seen in the fungal homologue, UapA. In addition, we show that a localisation deficient C-terminal truncation of SVCT1 blocks correct localisation of co-expressed, associated wildtype SVCT1. These results clearly show the importance of the dimer in both correct SVCT1 trafficking and transport activity.
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Journal articlePeck LD, Llewellyn T, Bennetot B, et al., 2024,
Horizontal transfers between fungal Fusarium species contributed to successive outbreaks of coffee wilt disease.
, PLoS Biol, Vol: 22Outbreaks of fungal diseases have devastated plants and animals throughout history. Over the past century, the repeated emergence of coffee wilt disease caused by the fungal pathogen Fusarium xylarioides severely impacted coffee production across sub-Saharan Africa. To improve the disease management of such pathogens, it is crucial to understand their genetic structure and evolutionary potential. We compared the genomes of 13 historic strains spanning 6 decades and multiple disease outbreaks to investigate population structure and host specialisation. We found that F. xylarioides comprised at least 4 distinct lineages: 1 host-specific to Coffea arabica, 1 to C. canephora var. robusta, and 2 historic lineages isolated from various Coffea species. The presence/absence of large genomic regions across populations, the higher genetic similarities of these regions between species than expected based on genome-wide divergence and their locations in different loci in genomes across populations showed that horizontal transfers of effector genes from members of the F. oxysporum species complex contributed to host specificity. Multiple transfers into F. xylarioides populations matched different parts of the F. oxysporum mobile pathogenicity chromosome and were enriched in effector genes and transposons. Effector genes in this region and other carbohydrate-active enzymes important in the breakdown of plant cell walls were shown by transcriptomics to be highly expressed during infection of C. arabica by the fungal arabica strains. Widespread sharing of specific transposons between F. xylarioides and F. oxysporum, and the correspondence of a putative horizontally transferred regions to a Starship (large mobile element involved in horizontal gene transfers in fungi), reinforce the inference of horizontal transfers and suggest that mobile elements were involved. Our results support the hypothesis that horizontal gene transfers contributed to the repeated emergence of coffee wilt di
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