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Journal articleWacker T, Helmstetter N, Wilson D, et al., 2023,
Two-speed genome evolution drives pathogenicity in fungal pathogens of animals., Proc Natl Acad Sci U S A, Vol: 120
The origins and evolution of virulence in amphibian-infecting chytrids Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are largely unknown. Here, we use deep nanopore sequencing of Bsal and comparative genomics against 21 high-quality genome assemblies that span the fungal Chytridiomycota. We discover that Bsal has the most repeat-rich genome of the Chytridiomycota, comprising 40.9% repetitive elements; this genome has expanded to more than 3× the length of its conspecific Bd, with autonomous and fully functional LTR/Gypsy elements contributing significantly to the expansion. The M36 metalloprotease virulence factors are highly expanded (n = 177) in Bsal, most of which (53%) are flanked by transposable elements, suggesting they have a repeat-associated expansion. We find enrichment upstream of M36 metalloprotease genes of three novel repeat families belonging to the repeat superfamily of LINEs that are implicated with gene copy number variations. Additionally, Bsal has a highly compartmentalized genome architecture, with virulence factors enriched in gene-sparse/repeat-rich compartments, while core conserved genes are enriched in gene-rich/repeat-poor compartments. Genes upregulated during infection are primarily found in the gene-sparse/repeat-rich compartment in both Bd and Bsal. Furthermore, genes with signatures of positive selection in Bd are enriched in repeat-rich regions, suggesting these regions are a cradle for the evolution of chytrid pathogenicity. These are the hallmarks of two-speed genome evolution, and this study provides evidence of two-speed genomes in an animal pathogen, shedding light on the evolution of fungal pathogens of vertebrates driving global declines and extinctions.
Journal articleShaw WM, Studena L, Roy K, et al., 2023,
Author Correction: Inducible expression of large gRNA arrays for multiplexed CRISPRai applications( doi 10.1038/s41467-022-32603-7, 25 augu , 20220, Nature Communications, Vol: 14, Pages: 1-1, ISSN: 2041-1723
Journal articlePeljto AL, Blumhagen RZ, Walts AD, et al., 2023,
Idiopathic pulmonary fibrosis is associated with common genetic variants and limited rare variants, American Journal of Respiratory and Critical Care Medicine, Vol: 207, Pages: 1194-1202, ISSN: 1073-449X
Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
Journal articleSun L, Zhang Q, Kong X, et al., 2023,
Highly efficient neutralizer-free L-malic acid production using engineered Saccharomyces cerevisiae, BIORESOURCE TECHNOLOGY, Vol: 370, ISSN: 0960-8524
Journal articleRobinson L, Collins A, Murphy R, et al., 2023,
Diversity and prevalence of type VI secretion system effectors in clinical Pseudomonas aeruginosa isolates, Frontiers in Microbiology, Vol: 13, ISSN: 1664-302X
Pseudomonas aeruginosa is an opportunistic pathogen and a major driver of morbidity and mortality in people with Cystic Fibrosis (CF). The Type VI secretion system (T6SS) is a molecular nanomachine that translocates effectors across the bacterial membrane into target cells or the extracellular environment enabling intermicrobial interaction. P. aeruginosa encodes three T6SS clusters, the H1-, H2- and H3-T6SS, and numerous orphan islands. Genetic diversity of T6SS-associated effectors in P. aeruginosa has been noted in reference strains but has yet to be explored in clinical isolates. Here, we perform a comprehensive bioinformatic analysis of the pangenome and T6SS effector genes in 52 high-quality clinical P. aeruginosa genomes isolated from CF patients and housed in the Personalised Approach to P. aeruginosa strain repository. We confirm that the clinical CF isolate pangenome is open and principally made up of accessory and unique genes that may provide strain-specific advantages. We observed genetic variability in some effector/immunity encoding genes and show that several well-characterised vgrG and PAAR islands are absent from numerous isolates. Our analysis shows clear evidence of disruption to T6SS genomic loci through transposon, prophage, and mobile genetic element insertions. We identified an orphan vgrG island in P. aeruginosa strain PAK and five clinical isolates using in silico analysis which we denote vgrG7, predicting a gene within this cluster to encode a Tle2 lipase family effector. Close comparison of T6SS loci in clinical isolates compared to reference P. aeruginosa strain PAO1 revealed the presence of genes encoding eight new T6SS effectors with the following putative functions: cytidine deaminase, lipase, metallopeptidase, NADase, and pyocin. Finally, the prevalence of characterised and putative T6SS effectors were assessed in 532 publicly available P. aeruginosa genomes, which suggests the existence of accessory effectors. Our in silico study of
Journal articlePates KM, Shang Z, Periselneris J, et al., 2023,
Breaking the mould, a first parse at natural language processing in aspergillosis diagnosis, Journal of Thoracic Disease, Vol: 15, Pages: 17-21, ISSN: 2072-1439
Journal articleWalls LE, Otoupal P, Ledesma-Amaro R, et al., 2023,
Bioconversion of cellulose into bisabolene using Ruminococcus flavefaciens and Rhodosporidium toruloides, Bioresource Technology, Vol: 368, ISSN: 0960-8524
In this study, organic acids were demonstrated as a promising carbon source for bisabolene production by the non-conventional yeast, Rhodosporidium toruloides, at microscale with a maximum titre of 1055 ± 7 mg/L. A 125-fold scale-up of the optimal process, enhanced bisabolene titres 2.5-fold to 2606 mg/L. Implementation of a pH controlled organic acid feeding strategy at this scale lead to a further threefold improvement in bisabolene titre to 7758 mg/L, the highest reported microbial titre. Finally, a proof-of-concept sequential bioreactor approach was investigated. Firstly, the cellulolytic bacterium Ruminococcus flavefaciens was employed to ferment cellulose, yielding 4.2 g/L of organic acids. R. toruloides was subsequently cultivated in the resulting supernatant, producing 318 ± 22 mg/L of bisabolene. This highlights the feasibility of a sequential bioprocess for the bioconversion of cellulose, into biojet fuel candidates. Future work will focus on enhancing organic acid yields and the use of real lignocellulosic feedstocks to further enhance bisabolene production.
Journal articleRimmer S, Barnacle J, Gibani M, et al., 2023,
The clinical presentation of monkeypox: a retrospective case-control study of patients with possible or probable monkeypox in a West London cohort, International Journal of Infectious Diseases, Vol: 126, Pages: 48-53, ISSN: 1201-9712
Objectives: Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in non-endemic countries. Our aim was to characterise diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification, and to describe a virtual care model.Methods: We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV PCR testing, 70 were confirmed positive and 70 negative. Data were compared to generate odds ratios of demographic and clinical features.Results: Positive patients were predominantly cis-male (99%) and self-identified as gay, bisexual and other men who have sex with men (GBMSM) (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (OR 7.69 [95% CI 3.58, 16.51]). Positive patients were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) compared with negative controls. 79% of patients engaged with virtual ward follow-up.Conclusions: These data can inform a risk-based approach to management of suspected monkeypox in GBMSM populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPXV outbreak.
Journal articleRusakov D, Menner A, Bismarck A, 2023,
High Porosity Poly(ether ketone ketone): Influence of Solvents on Foam Properties, Macromolecular Materials and Engineering, ISSN: 1438-7492
Poly(ether ketone ketone) (PEKK) is a semicrystalline high-performance polymer with exceptional mechanical properties, high continuous operation temperature, and is insoluble in most common solvents. Porous PEKK, desired for biomedical applications, is produced by a high-temperature thermally induced phase separation process using PEKK solutions in two high boiling aprotic solvents, 4-phenylphenol and 9-fluorenone, with concentrations up to 20 wt.%. It is demonstrated that the solvent choice has a pronounced influence on the phase separation behavior, which determines the foam morphology, physical and mechanical properties of PEKK foams. Porous PEKK with porosities ranging from 70% to 90%, specific surface areas up to 194 m2 g−1 and elastic moduli ranging from 35 to 100 MPa are produced.
Journal articleAdachi H, Sakai T, Harant AO, et al., 2023,
An atypical NLR protein modulates the NRC immune receptor network in Nicotiana benthamiana, PLOS GENETICS, Vol: 19, ISSN: 1553-7404
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