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Journal articleHowlett P, Gan J, Lesosky M, et al., 2024,
Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis.
, ThoraxBACKGROUND: Silicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship. METHODS: Web of Science, Medline and Embase were searched on 24 February 2023. Studies of radiographic, autopsy or death certificate silicosis, with an estimated average follow-up of over 20 years since first employment, were included. Cumulative silicosis risk methods were compared. The relative risks (RR) of silicosis at increasing cumulative exposures were calculated and used to estimate the absolute risk reduction (ARR). RESULTS: Eight eligible studies, including 10 cohorts, contributed 8792 cases of silicosis among 65 977 participants. Substantial differences in cumulative risk estimates between methodologies exist. Using the same method, we observed higher cumulative silicosis risks among mining compared with non-mining cohorts. A reduction from 4 to 2 mg/m³-years in cumulative RCS exposure corresponded to substantial risk reductions among miners (RR 0.23 (95% CI 0.18 to 0.29, I2=92.9%) with an ARR of 323 (95% CI 298 to 344) per 1000) and non-miners (RR 0.55 (95% CI 0.36 to 0.83, I2=77.0%) with an ARR of 23 (95% CI 9 to 33) per 1000). CONCLUSION: Despite significant heterogeneity, our findings support a reduction in permissible exposure limits from 0.1 mg/m3 to 0.05 mg/m³, particularly among mining populations. Further research is needed among non-miners as only two studies were eligible.
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Journal articleVersi A, Azim A, Ivan FX, et al., 2024,
Host-microbial interactions differ with age of asthma onset
, European Respiratory Journal, ISSN: 0903-1936Asthma is a heterogenous disease [1] and dichotomisation between childhood/early-onset (EO) and adult/late-onset (LO) disease [2] identified differences in lung function decline and response to anti-inflammatory therapies including biologics [3]. This suggests distinct inflammatory mechanisms underpin EO and LO asthma. In parallel, a relationship exists between airway neutrophilia and the airway microbiome [4, 5]. We postulate that differences in host-microbial interactions are associated with the age of asthma onset and would be maintained over time. Here, we applied a recently described machine learning framework, sparse canonical correlation analysis (Sparse-CCA) [6], to identify differences in host-microbial interactions in the airways of EO and LO asthma.
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Journal articleMeldrum OW, Donaldson GC, Narayana JK, et al., 2024,
Accelerated Lung Function Decline and Mucus-Microbe Evolution in Chronic Obstructive Pulmonary Disease.
, Am J Respir Crit Care Med, Vol: 210, Pages: 298-310Rationale: Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Objectives: Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. Methods: This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV1 decline (n = 30; accelerated decline; 156 ml/yr FEV1 loss) and with no FEV1 decline (n = 28; nondecline; 49 ml/yr FEV1 gain) over time. Lung microbiomes from paired sputum (total 116 specimens) were assessed by shotgun metagenomics and corresponding mucus profiles evaluated for biochemical and biophysical properties. Measurements and Main Results: Biochemical and biophysical mucus properties are significantly altered in the accelerated decline group. Unsupervised principal component analysis showed clear separation, with mucus biochemistry associated with accelerated decline, whereas biophysical mucus characteristics contributed to interindividual variability. When mucus and microbes are considered together, an accelerated decline mucus-microbiome association emerges, characterized by increased mucin (MUC5AC [mucin 5AC] and MUC5B [mucin 5B]) concentration and the presence of Achromobacter and Klebsiella. As COPD progresses, mucus-microbiome shifts occur, initially characterized by low mucin concentration and transition from viscous to elastic dominance accompanied by the commensals Veillonella, Gemella, Rothia, and Prevotella (Global Initiative for Chronic Obstructive Lung Disease [GOLD] A and B) before transition to increased mucus viscosity, mucins, and DNA concentration together with the emergence of pathogenic microorganisms including Haemophilus, Moraxella, and Pseudomonas (GOLD E). Conclusions: Mucus-microbiome associations evolve over time wi
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Journal articleSchyck S, Marchese P, Amani M, et al., 2024,
Harnessing Fungi Signaling in Living Composites
, Global Challenges, Vol: 8Signaling pathways in fungi offer a profound avenue for harnessing cellular communication and have garnered considerable interest in biomaterial engineering. Fungi respond to environmental stimuli through intricate signaling networks involving biochemical and electrical pathways, yet deciphering these mechanisms remains a challenge. In this review, an overview of fungal biology and their signaling pathways is provided, which can be activated in response to external stimuli and direct fungal growth and orientation. By examining the hyphal structure and the pathways involved in fungal signaling, the current state of recording fungal electrophysiological signals as well as the landscape of fungal biomaterials is explored. Innovative applications are highlighted, from sustainable materials to biomonitoring systems, and an outlook on the future of harnessing fungi signaling in living composites is provided.
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Journal articleBattersby JL, Stevens DA, Coutts RHA, et al., 2024,
The expanding mycovirome of Aspergilli
, Journal of Fungi, Vol: 10, ISSN: 2309-608XMycoviruses are viruses that infect fungi and are widespread across all major fungal taxa,exhibiting great biological diversity. Since their discovery in the 1960s, researchers have observeda myriad of fungal phenotypes altered due to mycoviral infection. In this review, we examine thenuanced world of mycoviruses in the context of the medically and agriculturally important fungalgenus, Aspergillus. The advent of RNA sequencing has revealed a previous underestimate of viralprevalence in fungi, in particular linear single-stranded RNA viruses, and here we outline the diverseviral families known to date that contain mycoviruses infecting Aspergillus. Furthermore, we describethese novel mycoviruses, highlighting those with peculiar genome structures, such as a split RNAdependent RNA polymerase gene. Next, we delineate notable mycovirus-mediated phenotypesin Aspergillus, in particular reporting on observations of mycoviruses that affect their fungal host’svirulence and explore how this may relate to virus-mediated decreased stress tolerance. Furthermore,mycovirus effects on microbial competition and antifungal resistance are discussed. The factors thatinfluence the manifestation of these phenotypes, such as temperature, fungal life stage, and infectionwith multiple viruses, among others, are also evaluated. In addition, we attempt to elucidate themolecular mechanisms that underpin these phenotypes, examining how mycoviruses can be targets,triggers, and even suppressors of RNA silencing and how this can affect fungal gene expression andphenotypes. Finally, we highlight the potential therapeutic applications of mycoviruses and how, inan approach analogous to bacteriophage therapy, their ability to produce hypovirulence in Aspergillusmight be used to attenuate invasive aspergillosis infections in humans.
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Journal articleBlank M, Wilson RC, Wan Y, et al., 2024,
Exploring real-world vancomycin target attainment in neonatal intensive care in the context of Staphylococcal infections: a retrospective observational cohort study
, Journal of Infection, Vol: 89, ISSN: 0163-4453 -
Journal articleShabestary K, Klemm C, Carling B, et al., 2024,
Phenotypic heterogeneity follows a growth-viability tradeoff in response to amino acid identity
, Nature Communications, Vol: 15, ISSN: 2041-1723In their natural environments, microorganisms mainly operate at suboptimal growth conditions with fluctuations in nutrient abundance. The resulting cellular adaptation is subject to conflicting tasks: growth or survival maximisation. Here, we study this adaptation by systematically measuring the impact of a nitrogen downshift to 24 nitrogen sources on cellular metabolism at the single-cell level. Saccharomyces lineages grown in rich media and exposed to a nitrogen downshift gradually differentiate to form two subpopulations of different cell sizes where one favours growth while the other favours viability with an extended chronological lifespan. This differentiation is asymmetrical with daughter cells representing the new differentiated state with increased viability. We characterise the metabolic response of the subpopulations using RNA sequencing, metabolic biosensors and a transcription factor-tagged GFP library coupled to high-throughput microscopy, imaging more than 800,000 cells. We find that the subpopulation with increased viability is associated with a dormant quiescent state displaying differences in MAPK signalling. Depending on the identity of the nitrogen source present, differentiation into the quiescent state can be actively maintained, attenuated, or aborted. These results establish amino acids as important signalling molecules for the formation of genetically identical subpopulations, involved in chronological lifespan and growth rate determination.
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Journal articleFu J, Zaghen S, Lu H, et al., 2024,
Reprogramming Yarrowia lipolytica metabolism for efficient synthesis of itaconic acid from flask to semipilot scale
, Science Advances, Vol: 10, ISSN: 2375-2548Itaconic acid is an emerging platform chemical with extensive applications. Itaconic acid is currently produced by Aspergillus terreus through biological fermentation. However, A. terreus is a fungal pathogen that needs additional morphology controls, making itaconic acid production on industrial scale problematic. Here, we reprogrammed the Generally Recognized As Safe (GRAS) yeast Yarrowia lipolytica for competitive itaconic acid production. After preventing carbon sink into lipid accumulation, we evaluated itaconic acid production both inside and outside the mitochondria while fine-tuning its biosynthetic pathway. We then mimicked the regulation of nitrogen limitation in nitrogen-replete conditions by down-regulating NAD+-dependent isocitrate dehydrogenase through weak promoters, RNA interference, or CRISPR interference. Ultimately, we optimized fermentation parameters for fed-batch cultivations and produced itaconic acid titers of 130.1 grams per liter in 1-liter bioreactors and 94.8 grams per liter in a 50-liter bioreactor on semipilot scale. Our findings provide effective approaches to harness the GRAS microorganism Y. lipolytica for competitive industrial-scale production of itaconic acid.
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Journal articleJaillais Y, Bayer E, Bergmann DC, et al., 2024,
Guidelines for naming and studying plasma membrane domains in plants.
, Nat Plants, Vol: 10, Pages: 1172-1183Biological membranes play a crucial role in actively hosting, modulating and coordinating a wide range of molecular events essential for cellular function. Membranes are organized into diverse domains giving rise to dynamic molecular patchworks. However, the very definition of membrane domains has been the subject of continuous debate. For example, in the plant field, membrane domains are often referred to as nanodomains, nanoclusters, microdomains, lipid rafts, membrane rafts, signalling platforms, foci or liquid-ordered membranes without any clear rationale. In the context of plant-microbe interactions, microdomains have sometimes been used to refer to the large area at the plant-microbe interface. Some of these terms have partially overlapping meanings at best, but they are often used interchangeably in the literature. This situation generates much confusion and limits conceptual progress. There is thus an urgent need for us as a scientific community to resolve these semantic and conceptual controversies by defining an unambiguous nomenclature of membrane domains. In this Review, experts in the field get together to provide explicit definitions of plasma membrane domains in plant systems and experimental guidelines for their study. We propose that plasma membrane domains should not be considered on the basis of their size alone but rather according to the biological system being considered, such as the local membrane environment or the entire cell.
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Journal articlePennisi I, Cavuto ML, Miglietta L, et al., 2024,
Rapid, portable, and electricity-free sample extraction method for enhanced molecular diagnostics in resource-limited settings
, Analytical Chemistry, Vol: 96, Pages: 11181-11188, ISSN: 0003-2700The COVID-19 pandemic has highlighted the need for rapid and reliable diagnostics that are accessible in resource-limited settings. To address this pressing issue, we have developed a rapid, portable, and electricity-free method for extracting nucleic acids from respiratory swabs (i.e. nasal, nasopharyngeal and buccal swabs), successfully demonstrating its effectiveness for the detection of SARS-CoV-2 in residual clinical specimens. Unlike traditional approaches, our solution eliminates the need for micropipettes or electrical equipment, making it user-friendly and requiring little to no training. Our method builds upon the principles of magnetic bead extraction and revolves around a low-cost plastic magnetic lid, called SmartLid, in combination with a simple disposable kit containing all required reagents conveniently prealiquoted. Here, we clinically validated the SmartLid sample preparation method in comparison to the gold standard QIAamp Viral RNA Mini Kit from QIAGEN, using 406 clinical isolates, including 161 SARS-CoV-2 positives, using the SARS-CoV-2 RT-qPCR assays developed by the US Centers for Disease Control and Prevention (CDC). The SmartLid method showed an overall sensitivity of 95.03% (95% CI: 90.44-97.83%) and a specificity of 99.59% (95% CI: 97.76-99.99%), with a positive agreement of 97.79% (95% CI: 95.84-98.98%) when compared to QIAGEN's column-based extraction method. There are clear benefits to using the SmartLid sample preparation kit: it enables swift extraction of viral nucleic acids, taking less than 5 min, without sacrificing significant accuracy when compared to more expensive and time-consuming alternatives currently available on the market. Moreover, its simplicity makes it particularly well-suited for the point-of-care where rapid results and portability are crucial. By providing an efficient and accessible means of nucleic acid extraction, our approach aims to introduce a step-change in diagnostic capabilities for resource-limited sett
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