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Journal articleEhsan M, Ghani L, Lan B, et al., 2025,
Unsymmetric triazine‐based triglucoside detergents for membrane protein stability
, ChemBioChem: a European journal of chemical biology, Vol: 26, ISSN: 1439-4227Membrane proteins play a crucial role in a variety of biological processes and are key targets for pharmaceutical development. Structural studies of membrane proteins provide molecular insights into the mechanisms of these processes and are essential for effective drug discovery. Historically, these studies have relied on solubilization of the target protein using detergents, but conventional detergents often fail to maintain the stability of challenging membrane proteins. To address this issue, there is a need to develop novel detergents with enhanced protein stabilization properties. In this study, we synthesized unsymmetric variants of recently reported tris(hydroxymethyl)aminomethane(TRIS)-linker-bearing triazine-based triglucosides (TTGs) by incorporating two different alkyl chains (long and short) into the detergent structure. When tested with model membrane proteins, including a G protein-coupled receptor, TTG-8,12 demonstrated superior efficacy in stabilizing membrane proteins compared to the original TTGs and the gold standard detergents DDM/LMNG. These results suggest that detergent unsymmetry is an important concept for improving detergent performance and unsymmetric detergents such as TTG-8,12 hold significant potential for advancing membrane protein structural studies.
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Journal articleRafieenia R, Klemm C, Hapeta P, et al., 2025,
Designing synthetic microbial communities with the capacity to upcycle fermentation byproducts to increase production yields
, Trends in Biotechnology, Vol: 43, Pages: 601-619, ISSN: 0167-7799Microbial cell factories, which convert feedstocks into a product of value, have the potential to help transition toward a bio-based economy with more sustainable ways to produce food, fuels, chemicals, and materials. One common challenge found in most bioconversions is the co-production, together with the product of interest, of undesirable byproducts or overflow metabolites. Here, we designed a strategy based on synthetic microbial communities to address this issue and increase overall production yields. To achieve our goal, we created a Yarrowia lipolytica co-culture comprising a wild-type (WT) strain that consumes glucose to make biomass and citric acid (CA), and an ‘upcycler’ strain, which consumes the CA produced by the WT strain. The co-culture produced up to two times more β-carotene compared with the WT monoculture using either minimal medium or hydrolysate. The proposed strategy has the potential to be applied to other bioprocesses and organisms.
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Journal articleNarayana JK, Mac Aogáin M, Hansbro PM, et al., 2025,
The bronchiectasis microbiome: current understanding and treatment implications.
, Curr Opin Pulm Med, Vol: 31, Pages: 135-144PURPOSE OF REVIEW: Advances in DNA sequencing and analysis of the respiratory microbiome highlight its close association with bronchiectasis phenotypes, revealing fresh opportunities for diagnosis, stratification, and personalized clinical intervention. An under-recognized condition, bronchiectasis is increasingly the subject of recent large-scale, multicentre, and longitudinal clinical studies including detailed analysis of the microbiome. In this review, we summarize recent progress in our understanding of the bronchiectasis microbiome within the context of its potential use in treatment decisions. RECENT FINDINGS: Diverse microbiome profiles exist in bronchiectasis, in line with the established disease heterogeneity including treatment response. Classical microbiology has established Pseudomonas aeruginosa and Haemophilus influenza as two microbial markers of disease, while holistic microbiome analysis has uncovered important associations with less common bacterial taxa including commensal an/or pathobiont species, including the emerging role of the fungal mycobiome, virome, and interactome. Integration of airway microbiomes with other high-dimensional biological and clinical datasets holds significant promise to determining treatable traits and mechanisms of disease related to the microbiome. SUMMARY: The bronchiectasis microbiome is an emerging and key area of study with significant implications for understanding bronchiectasis, influencing treatment decisions and ultimately improving patient outcomes.
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Journal articleBrandfellner L, Bismarck A, Müller HW, 2025,
Time for polymers: Onset of drag reduction in the Reynolds-Weissenberg-plane
, Physics of Fluids, Vol: 37, ISSN: 1070-6631The flow of dilute aqueous polyacrylamide PAAm solutions with varying polymer molecular weight was studied in turbulent pipe flow. Scans in Reynolds number Re were performed in Newtonian turbulent flow [pre drag reduction (DR) onset] and intermediate DR flow. Polymer degradation shifted the onset of DR to higher Re. Polymer relaxation times derived from molecular weight and viscosity contribution of the polymer combined with the shear rate of the flow were used to calculate the Weissenberg number Wi. Fanning friction factors f derived from experimental data were fitted as a function of Re and flow distance to obtain flow properties for any state of polymer degradation and at any Re. From this fit function the onset of DR for varying polymer molecular weight was derived in the Re-Wi plane and the flow regimes accessed with increasing Re at constant molecular weight were identified. Trends in DR onset strongly depend on the shear rate used to calculate Wi. The elasticity number El was only independent of Re when Wi was determined from volume shear rate instead of the wall shear rate. Our observations indicate that DR is dominated by processes in the volume rather than those occurring at the wall.
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Journal articleBiegler V, Schaubeder JB, Selinger J, et al., 2025,
Effect of xylan on the mechanical performance of softwood kraft pulp 2D papers and 3D foams
, Tappi Journal, Vol: 2025-March, Pages: 131-141, ISSN: 0734-1415Pulp fibers are paramount in paper products and have lately seen emerging use in fiber foams. Xylan, an integral component in pulp fibers, is known to contribute to paper strength, but its effect on the strength of pulp fiber foams remains less explored. In this study, we investigate the role of xylan in both 2D handsheets and 3D foams. For a softwood kraft pulp, we enzymatically removed 1% from pulp fibers and added 3% xylan to them by adsorption, corresponding to approximately a decrease of a tenth and an increase of a third of the total xylan content. The mechanical properties of 2D fiber networks, i.e., handsheets, made using the xylan-enriched pulp improved, particularly regarding tensile strength and Young’s modulus; however, the decrease in mechanical properties of handsheets made from enzymatically-treated xylan-depleted pulp was more pronounced. In 3D networks – pulp fiber foams, much less fiber-fiber contacts formed, and thus the mechanical properties were not as much influenced by removal of xylan. Furthermore, the presence of the required surfactant on the fibers, acting as debonding agent, overshadows any positive effect xylan might have on fiber-fiber bonding. We propose that the improved mechanical properties for the sheets result from a combination of an increased number of fiber-fiber bonds and higher sheet density, while the deterioration in mechanical properties of handsheets comprising enzymatically-treated fibers is caused by the opposite effect.
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Journal articleFerrando-Marco M, Barkoulas M, 2025,
EFL-3/E2F7 modulates Wnt signalling by repressing the Nemo-like kinase LIT-1 during asymmetric epidermal cell division in Caenorhabditis elegans.
, Development, Vol: 152The E2F family of transcription factors is conserved in higher eukaryotes and plays pivotal roles in controlling gene expression during the cell cycle. Most canonical E2Fs associate with members of the Dimerisation Partner (DP) family to activate or repress target genes. However, atypical repressors, such as E2F7 and E2F8, lack DP interaction domains and their functions are less understood. We report here that EFL-3, the E2F7 homologue of Caenorhabditis elegans, regulates epidermal stem cell differentiation. We show that phenotypic defects in efl-3 mutants depend on the Nemo-like kinase LIT-1. EFL-3 represses lit-1 expression through direct binding to a lit-1 intronic element. Increased LIT-1 expression in efl-3 mutants reduces POP-1/TCF nuclear distribution, and consequently alters Wnt pathway activation. Our findings provide a mechanistic link between an atypical E2F family member and NLK during C. elegans asymmetric cell division, which may be conserved in other animals.
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Journal articleRueda-Maíllo F, Garrido-Jurado I, Kotta-Loizou I, et al., 2025,
A mycoviral infection drives virulence and ecological fitness of the entomopathogenic fungus Beauveria bassiana
, Journal of Invertebrate Pathology, Vol: 209, ISSN: 0022-2011Entomopathogenic 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 articleWang L-L, Shen X, Xie Y, et al., 2025,
A gut Eggerthella lenta-derived metabolite impairs neutrophil function to aggravate bacterial lung infection.
, Sci Transl Med, Vol: 17The composition of the gut microbiota in patients with bronchiectasis has been proven to be distinct from that of healthy individuals, and this disrupted gut microbiota can exacerbate lung infections. However, the responsible microbes and mechanisms in the "gut-lung" axis in bronchiectasis remain unknown. Here, we report that Eggerthella lenta was enriched in the gut, and taurine ursodeoxycholic acid (TUDCA) was enriched in both the guts and sera of patients with bronchiectasis, with both being associated with disease severity. Fecal microbiota transfer from patients with bronchiectasis as well as administration of E. lenta independently exacerbated pulmonary Pseudomonas aeruginosa infections in murine models. E. lenta-associated TUDCA bound adenosine monophosphate-activated protein kinase (AMPK) within neutrophils and interfered with the interaction between liver kinase B1 and AMPK, with a consequential decrease in AMPK phosphorylation. This ultimately reduced ATP production in neutrophils, inhibited their function, and compromised P. aeruginosa elimination from the lung, aggravating tissue injury. Metformin treatment improved disease severity and outcome in the mouse models. In sum, the gut bacterium E. lenta raises the stakes of bacterial lung infection because it causes dysfunction of neutrophils circulated from serum to lung via the metabolite TUDCA. Interventions targeting E. lenta or AMPK phosphorylation may serve as adjunctive strategies to complement existing approaches for managing chronic pulmonary infection in bronchiectasis and other chronic respiratory disease states.
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Journal articleHowlett P, Ehrlich R, 2025,
Confronting the growing epidemic of silicosis and TB among small-scale miners
, The Lancet Public Health, ISSN: 2468-2667An estimated 49.5 million small-scale miners (SSM) globally are exposed to veryhigh levels of silica during their work. The substantial morbidity and mortality ofsilicosis and tuberculosis (TB) among workers exposed to such levels have beenclearly documented. This Viewpoint raises concern at the failure to respond to agrowing epidemic of lung disease – predominantly silicosis and TB – among SSM.We structure our argument around five points.First, we outline the huge burden of lung disease among SSM. Current estimates ofdisease prevalence yield approximately 450,000 microbiologically confirmedprevalent TB cases and 2.75 million prevalent silicosis cases globally among SSM.Second, we critically examine these figures in the context of high silica exposures.Given the very high intensities reported among SSM, between four and 2400 timesthe United States Permissible Exposure Limit, we believe the reported highprevalences of silicosis and TB are plausible. Third, we illustrate the failure tosupport research that aims to understand and mitigate the epidemic of silicosis andTB among SSM. Fourth, we examine the historic, socioeconomic and political factorsshaping the current epidemic. The small-scale mining industry has grown rapidlyover two decades, driven by upstream factors such as unemployment, climatechange and the growing mineral demand. These continued pressures suggest thatthis growth will accelerate. Finally, we recommend solutions appropriate to the earlystages of a response and the large-scale mobilization required. A funded globalplatform to bring together stakeholders is needed to facilitate research and action. Akey intervention is silica dust reduction, building on studies which demonstrateeffective and inexpensive technologies and practices.We conclude that an urgent and coordinated response is needed to address thedevastating health impacts of silicosis and TB in SSM and their preventableworkplace causes.
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Thesis dissertationVersi A, 2025,
Analysis of microbiome-based asthma phenotypes
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