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Journal articleQuintero Santofimio V, Amaral A, Feary J, 2024,
Occupational exposures in low- and middle-income countries: a scoping review
, PLOS Global Public Health, Vol: 4, ISSN: 2767-3375Exposure to high levels of harmful agents in the workplace can significantly impact workers’ health, contributing to morbidity and mortality. Levels of these exposures are often measured in high-income countries in research studies and, in some places, to monitor levels in line with health and safety regulations. However, less is known about workplace exposure levels in low- and middle-income countries (LMICs). Our aim was to describe the quantitative exposure measurements of different occupational agents across industries within LMICs. We conducted a scoping review of peer-reviewed publications available on Web of Science and PubMed from inception to 1 September 2023. Our search focused on quantitative occupational exposure measurements across industries in LMICs. We identified a total of 8,676 publications. After screening, 58 studies from 25 countries were retained for final review. China, Iran, and Tanzania contributed the greatest number of studies. Manufacturing, mining, and agriculture were the most studied sectors, with factory workers and miners being the most common job titles. Exposure measurements included vapour, gases, dust, and fumes (VGDF), solvents, metals, pesticides and particulate matter. Occupational exposure levels for the same industry varied widely across geographical regions. This review provides a comprehensive overview of occupational exposures in LMICs and highlights the absence of data in certain geographical areas and industries. The study contributes valuable insights for directing future research, and the need to optimise the assessment of occupational exposures in LMICs with the aim ultimately of reducing disease.
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Thesis dissertationIrakleidi DA, 2024,
The Rtc RNA Repair System in E. coli: underlying molecular regulation and its role in infection and antibiotic resistance.
The Rtc RNA repair system, comprising of the RNA cyclase RtcA, the RNA ligase RtcB and the transcriptional activator RtcR, is present in many bacterial species causing human diseases, including the model organisms and putative pathogens Escherichia coli and Salmonella enterica, and has been suggested to play a role in the development of antibiotic resistance. Here we explore the events underlying Rtc activation via RtcR and its CRISPR-associated Rossmann fold (CARF) domain as well as its physiological role during infection. In vitro transcription and ATPase assays showcased the inherent inhibition exerted by the RtcR CARF domain towards RtcR activation as well as its recognition of 2’,3’cP RNA termini – known to act as substrates for the system’s ligase, RtcB – as inducing ligands. End-labelling as well as adapter ligation with RtcB of in vivo bound RNA extracts derived from wildtype or N-terminal truncated RtcR provides evidence for the in vivo association of 2’,3’cP-RNA molecules with RtcR. Β-galactosidase assays demonstrated more prominent rtcBA expression in the rtc-inducing ΔhisT and Δrna E. coli mutants when compared to the wildtype, regardless of nutrient abundance. rtcBA expression appears at least partly RtcR-dependent, relying on certain inverted repeats, possibly carrying RtcR binding sites, located at specific positions in the rtcBA promoter. Pathogenicity assays using the infection model G. mellonella demonstrated that wildtype E. coli K12 MG1655 cells are more virulent in vivo compared to variants lacking any of the Rtc components or the functionally important RtcR CARF domain. Complementation of rtc gene deletions with wildtype Rtc proteins, but not functionally catalytic mutants, reverses the infection phenotype to that of wildtype. Post-infection treatment of larvae with the ribosome-targeting antibiotics chloramphenicol and tetracycline fails at affecting the survival rates of larvae infect
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Journal articleFisher MC, Burnett F, Chandler C, et al., 2024,
A one health roadmap towards understanding and mitigating emerging Fungal Antimicrobial Resistance: fAMR
, npj Antimicrobials and Resistance, Vol: 2, ISSN: 2731-8745The emergence of fungal antimicrobial resistance—fAMR—is having a growing impact on human and animal health, and food security. This roadmap charts inter-related actions that will enhance our ability to mitigate the risk of fAMR. As humanity’s reliance on antifungal chemicals escalates, our understanding of their one-health consequences needs to scale accordingly if we are to protect our ability to manage the global spectrum of fungal disease sustainably.
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Journal articleMalci K, Li IS, Kisseroudis N, et al., 2024,
Modulating Microbial Materials - Engineering Bacterial Cellulose with Synthetic Biology
, ACS SYNTHETIC BIOLOGY, Vol: 13, Pages: 3857-3875, ISSN: 2161-5063 -
Journal articleNgo LT, Rekowski MJ, Koestler DC, et al., 2024,
Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.
, ERJ Open Res, Vol: 10, ISSN: 2312-0541BACKGROUND: Idiopathic interstitial pneumonias (IIPs), such as idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features, present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). METHODS: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared with controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles that were then analysed to predict survival outcomes and investigate associated pathways. RESULTS: Proteomic profiling successfully differentiated IIP from controls. k-means clustering based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology index (concordance index 0.794 versus 0.709). The cluster with the worst prognosis featured decreased inflammatory signalling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B-cell-mediated immunity. CONCLUSIONS: The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalised treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.
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Journal articleLin L, Ledesma-Amaro R, Ji X-J, et al., 2024,
Harnessing oleaginous yeast to produce omega fatty acids
, TRENDS IN BIOTECHNOLOGY, Vol: 42, Pages: 1335-1338, ISSN: 0167-7799 -
Journal articleOikawa K, Fujisaki K, Shimizu M, et al., 2024,
The blast pathogen effector AVR-Pik binds and stabilizes rice heavy metal-associated (HMA) proteins to co-opt their function in immunity
, PLOS PATHOGENS, Vol: 20, ISSN: 1553-7366 -
Journal articleMadhuprakash J, Toghani A, Contreras MP, et al., 2024,
A disease resistance protein triggers oligomerization of its NLR helper into a hexameric resistosome to mediate innate immunity
, Science Advances, Vol: 10, ISSN: 2375-2548NRCs are essential helper NLR (nucleotide-binding domain and leucine-rich repeat) proteins that execute immune responses triggered by sensor NLRs. The resting state of NbNRC2 was recently shown to be a homodimer, but the sensor-activated state remains unclear. Using cryo-EM, we determined the structure of sensor-activated NbNRC2, which forms a hexameric inflammasome-like resistosome. Mutagenesis of the oligomerization interface abolished immune signaling, confirming the functional significance of the NbNRC2 resistosome. Comparative structural analyses between the resting state homodimer and sensor-activated homohexamer revealed substantial rearrangements, providing insights into NLR activation mechanisms. Furthermore, structural comparisons between NbNRC2 hexamer and previously reported CC-NLR pentameric assemblies revealed features allowing an additional protomer integration. Using the NbNRC2 hexamer structure, we assessed the recently released AlphaFold 3 for predicting activated CC-NLR oligomers, revealing high-confidence modeling of NbNRC2 and other CC-NLR amino-terminal α1 helices, a region proven difficult to resolve structurally. Overall, our work sheds light on NLR activation mechanisms and expands understanding of NLR structural diversity.
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Journal articleChotirmall SH, Chang AB, Chalmers JD, 2024,
Infection vs Inflammation The Bronchiectasis " Tug Of War "
, CHEST, Vol: 166, Pages: 928-930, ISSN: 0012-3692 -
Journal articleWee LE, Tan JYJ, Chiew CJ, et al., 2024,
Response.
, Chest, Vol: 166, Pages: e167-e168
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