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Article ; Online: Dose-Dependent Genetic Resistance to Azole Fungicides Found in the Apple Scab Pathogen.

Heaven, Thomas / Armitage, Andrew D / Xu, Xiangming / Goddard, Matthew R / Cockerton, Helen M

2023 Volume 9, Issue 12

Abstract: The evolution of azole resistance in fungal pathogens presents a major challenge in both crop production and human health. Apple orchards across the world are faced with the emergence of azole fungicide resistance in the apple scab ... ...

Abstract	The evolution of azole resistance in fungal pathogens presents a major challenge in both crop production and human health. Apple orchards across the world are faced with the emergence of azole fungicide resistance in the apple scab pathogen
Language	English
Publishing date	2023-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof9121136
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: A Genomic Resource for the Strawberry Powdery Mildew Pathogen

Heaven, Thomas / Cockerton, Helen M / Xu, Xiangming / Goddard, Matthew / Armitage, Andrew D

Phytopathology

2023 Volume 113, Issue 2, Page(s) 355–359

Abstract: Powdery mildew is one of the most economically destructive diseases in protected strawberry production. Here we present the first genome assembly ... ...

Abstract	Powdery mildew is one of the most economically destructive diseases in protected strawberry production. Here we present the first genome assembly for
MeSH term(s)	Fragaria/microbiology ; Plant Diseases/microbiology ; Ascomycota/genetics ; Erysiphe ; Genomics
Language	English
Publishing date	2023-02-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	208889-7
ISSN	1943-7684 ; 0031-949X
ISSN (online)	1943-7684
ISSN	0031-949X
DOI	10.1094/PHYTO-03-22-0091-A
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Article ; Online: UCSF ChimeraX: Tools for structure building and analysis.

Meng, Elaine C / Goddard, Thomas D / Pettersen, Eric F / Couch, Greg S / Pearson, Zach J / Morris, John H / Ferrin, Thomas E

Protein science : a publication of the Protein Society

2023 Volume 32, Issue 11, Page(s) e4792

Abstract: Advances in computational tools for atomic model building are leading to accurate models of large molecular assemblies seen in electron microscopy, often at challenging resolutions of 3-4 Å. We describe new methods in the UCSF ChimeraX molecular modeling ...

Abstract	Advances in computational tools for atomic model building are leading to accurate models of large molecular assemblies seen in electron microscopy, often at challenging resolutions of 3-4 Å. We describe new methods in the UCSF ChimeraX molecular modeling package that take advantage of machine-learning structure predictions, provide likelihood-based fitting in maps, and compute per-residue scores to identify modeling errors. Additional model-building tools assist analysis of mutations, post-translational modifications, and interactions with ligands. We present the latest ChimeraX model-building capabilities, including several community-developed extensions. ChimeraX is available free of charge for noncommercial use at https://www.rbvi.ucsf.edu/chimerax.
MeSH term(s)	Software ; Cryoelectron Microscopy/methods ; Likelihood Functions ; Models, Molecular ; Microscopy, Electron ; Protein Conformation
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1106283-6
ISSN	1469-896X ; 0961-8368
ISSN (online)	1469-896X
ISSN	0961-8368
DOI	10.1002/pro.4792
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Article ; Online: Dose-Dependent Genetic Resistance to Azole Fungicides Found in the Apple Scab Pathogen

Thomas Heaven / Andrew D. Armitage / Xiangming Xu / Matthew R. Goddard / Helen M. Cockerton

Journal of Fungi, Vol 9, Iss 12, p

2023 Volume 1136

Abstract	The evolution of azole resistance in fungal pathogens presents a major challenge in both crop production and human health. Apple orchards across the world are faced with the emergence of azole fungicide resistance in the apple scab pathogen Venturia inaequalis . Target site point mutations observed in this fungus to date cannot fully explain the reduction in sensitivity to azole fungicides. Here, polygenic resistance to tebuconazole was studied across a population of V. inaequalis . Genotyping by sequencing allowed Quantitative Trait Loci (QTLs) mapping to identify the genetic components controlling this fungicide resistance. Dose-dependent genetic resistance was identified, with distinct genetic components contributing to fungicide resistance at different exposure levels. A QTL within linkage group seven explained 65% of the variation in the effective dose required to reduce growth by 50% (ED 50 ). This locus was also involved in resistance at lower fungicide doses (ED 10 ). A second QTL in linkage group one was associated with dose-dependent resistance, explaining 34% of variation at low fungicide doses (ED 10 ), but did not contribute to resistance at higher doses (ED 50 and ED 90 ). Within QTL regions, non-synonymous mutations were observed in several ATP-Binding Cassette and Major Facilitator SuperFamily transporter genes. These findings provide insight into the mechanisms of fungicide resistance that have evolved in horticultural pathogens. Identification of resistance gene candidates supports the development of molecular diagnostics to inform management practices.
Keywords	quantitative trait loci (QTLs) ; plant pathogen ; biotroph ; linkage map ; genotyping by sequencing ; single nucleotide polymorphism (SNP) ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: A Genomic Resource for the Strawberry Powdery Mildew Pathogen Podosphaera aphanis

Heaven, Thomas / Cockerton, Helen M. / Xu, Xiangming / Goddard, Matthew / Armitage, Andrew D.

Phytopathology®. 2023 Feb., v. 113, no. 2 p.355-359

2023

Abstract: Powdery mildew is one of the most economically destructive diseases in protected strawberry production. Here we present the first genome assembly for Podosphaera aphanis, the causal agent of powdery mildew on strawberry. This obligate-biotrophic fungal ... ...

Abstract	Powdery mildew is one of the most economically destructive diseases in protected strawberry production. Here we present the first genome assembly for Podosphaera aphanis, the causal agent of powdery mildew on strawberry. This obligate-biotrophic fungal pathogen was sampled from a naturally occurring outbreak on Fragaria × ananassa ‘Malling Centenary’ plants grown under cover in the United Kingdom. Assembled reads resolved a 55.6 Mb genome, composed of 12,357 contigs whose annotation led to prediction of 17,239 genes encoding 17,328 proteins. The genome is highly-complete, with 97.5% of conserved single-copy Ascomycete genes shown to be present. This annotated P. aphanis genome provides a molecular resource for further investigation into host−pathogen interactions in the strawberry powdery mildew pathosystem.
Keywords	Fragaria ananassa ; Podosphaera aphanis ; fungi ; genome ; genome assembly ; genomics ; pathogens ; powdery mildew ; prediction ; strawberries ; United Kingdom ; biotroph ; Fragaria ; horticulture ; mycology ; Rubus ; Sphaerotheca macularis
Language	English
Dates of publication	2023-02
Size	p. 355-359.
Publishing place	The American Phytopathological Society
Document type	Article ; Online
ZDB-ID	208889-7
ISSN	1943-7684 ; 0031-949X
ISSN (online)	1943-7684
ISSN	0031-949X
DOI	10.1094/PHYTO-03-22-0091-A
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A common regulatory haplotype doubles lactoferrin concentration in milk.

Lopdell, Thomas J / Trevarton, Alexander J / Moody, Janelle / Prowse-Wilkins, Claire / Knowles, Sarah / Tiplady, Kathryn / Chamberlain, Amanda J / Goddard, Michael E / Spelman, Richard J / Lehnert, Klaus / Snell, Russell G / Davis, Stephen R / Littlejohn, Mathew D

Genetics, selection, evolution : GSE

2024 Volume 56, Issue 1, Page(s) 22

Abstract: Background: Bovine lactoferrin (Lf) is an iron absorbing whey protein with antibacterial, antiviral, and antifungal activity. Lactoferrin is economically valuable and has an extremely variable concentration in milk, partly driven by environmental ... ...

Abstract	Background: Bovine lactoferrin (Lf) is an iron absorbing whey protein with antibacterial, antiviral, and antifungal activity. Lactoferrin is economically valuable and has an extremely variable concentration in milk, partly driven by environmental influences such as milking frequency, involution, or mastitis. A significant genetic influence has also been previously observed to regulate lactoferrin content in milk. Here, we conducted genetic mapping of lactoferrin protein concentration in conjunction with RNA-seq, ChIP-seq, and ATAC-seq data to pinpoint candidate causative variants that regulate lactoferrin concentrations in milk. Results: We identified a highly-significant lactoferrin protein quantitative trait locus (pQTL), as well as a cis lactotransferrin (LTF) expression QTL (cis-eQTL) mapping to the LTF locus. Using ChIP-seq and ATAC-seq datasets representing lactating mammary tissue samples, we also report a number of regions where the openness of chromatin is under genetic influence. Several of these also show highly significant QTL with genetic signatures similar to those highlighted through pQTL and eQTL analysis. By performing correlation analysis between these QTL, we revealed an ATAC-seq peak in the putative promotor region of LTF, that highlights a set of 115 high-frequency variants that are potentially responsible for these effects. One of the 115 variants (rs110000337), which maps within the ATAC-seq peak, was predicted to alter binding sites of transcription factors known to be involved in lactation-related pathways. Conclusions: Here, we report a regulatory haplotype of 115 variants with conspicuously large impacts on milk lactoferrin concentration. These findings could enable the selection of animals for high-producing specialist herds.
MeSH term(s)	Animals ; Female ; Haplotypes ; Lactation/genetics ; Lactoferrin/genetics ; Lactoferrin/analysis ; Lactoferrin/metabolism ; Milk/chemistry ; Milk/metabolism ; Cattle
Chemical Substances	Lactoferrin (EC 3.4.21.-)
Language	English
Publishing date	2024-03-28
Publishing country	France
Document type	Journal Article
ZDB-ID	1005838-2
ISSN	1297-9686 ; 0754-0264 ; 0999-193X
ISSN (online)	1297-9686
ISSN	0754-0264 ; 0999-193X
DOI	10.1186/s12711-024-00890-x
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Article: Anti-synthetase syndrome associated interstitial lung disease after combination dual immune checkpoint inhibition.

Bell, Peter T / Beaton, Thomas / Terrill, Matthew / Gillis, David / Goddard, John

Respirology case reports

2023 Volume 11, Issue 4, Page(s) e01115

Abstract: Immune checkpoint inhibitors (ICIs) unleash potent anti-tumour responses but with frequent off-target immune-mediated adverse events (irAE). ICIs can induce a spectrum of rheumatologic manifestations including inflammatory arthritis, Sjögren's syndrome, ... ...

Abstract	Immune checkpoint inhibitors (ICIs) unleash potent anti-tumour responses but with frequent off-target immune-mediated adverse events (irAE). ICIs can induce a spectrum of rheumatologic manifestations including inflammatory arthritis, Sjögren's syndrome, scleroderma and systemic lupus erythematosus. Here, we describe a case of antisynthetase syndrome associated interstitial lung disease (ILD) following dual Programmed Cell Death 1 and Cytotoxic T Lymphocyte-Associated Protein 4 checkpoint inhibition in a patient with metastatic melanoma. Initial treatment course was complicated by a number of irAEs including pneumonitis, colitis and thyroiditis. Suspicion of an underlying systemic rheumatic disease was heightened by the severe, relapsing and fibrosing nature of the interstitial pneumonitis. A diagnosis of amyopathic antisynthetase syndrome was made upon detection of circulating aminoacyl-tRNA synthetase (anti-EJ) autoantibodies. Intensification of induction immunosuppression followed by maintenance mycophenolate, prednisone and monthly intravenous immunoglobulin achieved long-term disease control. Detection of de novo ICI-induced inflammatory myositis ILD requires a high index of suspicion and carries important prognostic and treatment implications.
Language	English
Publishing date	2023-03-13
Publishing country	United States
Document type	Case Reports
ZDB-ID	2750180-2
ISSN	2051-3380
ISSN	2051-3380
DOI	10.1002/rcr2.1115
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Article ; Online: Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis.

Bruorton, Matthew / Donnelley, Martin / Goddard, Thomas / O'Connor, Antonia / Parsons, David / Phillips, Jessica / Carson-Chahhoud, Kristin / Tai, Andrew

BMJ open

2024 Volume 14, Issue 2, Page(s) e080034

Abstract: Introduction: Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry (XV) is a novel form of X- ... ...

Abstract	Introduction: Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry (XV) is a novel form of X-ray imaging that can generate lung ventilation data through the breathing cycle. XV technology has been validated in multiple animal models, including the β-ENaC mouse model of CF lung disease. It has since been assessed in early-phase clinical trials in adult human subjects; however, there is a paucity of data in the paediatric cohort, including in CF. The aim of this pilot study was to investigate the feasibility of performing a single-centre cohort study in paediatric patients with CF and in those with normal lungs to demonstrate the appropriateness of proceeding with further studies of XV in these cohorts. Methods and analysis: This is a cross-sectional, single-centre, pilot study. It will recruit children aged 3-18 years to have XV lung imaging performed, as well as paired pulmonary function testing. The study will aim to recruit 20 children without CF with normal lungs and 20 children with CF. The primary outcome will be the feasibility of recruiting children and performing XV testing. Secondary outcomes will include comparisons between XV and current assessments of pulmonary function and structure. Ethics and dissemination: This project has ethical approval granted by The Women's and Children's Hospital Human Research Ethics Committee (HREC ID 2021/HRE00396). Findings will be disseminated through peer-reviewed publication and conferences. Trial registration number: ACTRN12623000109606.
MeSH term(s)	Adult ; Animals ; Mice ; Child ; Humans ; Female ; Cystic Fibrosis/diagnostic imaging ; Cystic Fibrosis/complications ; Pilot Projects ; X-Rays ; Cohort Studies ; Cross-Sectional Studies ; Lung/diagnostic imaging
Language	English
Publishing date	2024-02-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-080034
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Article ; Online: Effect of Perioperative Antithrombotics on Postoperative Transfusion and Hematoma in Head and Neck Free Flaps.

Hicks, Melanie D / Vasudev, Milind / Bishop, Jessica L / Garcia, Natalie / Chowdhury, Farshad / Pham, Tiffany T / Heslop, Gabriela / Greene, Benjamin / Jeyarajan, Hari / Grayson, Jessica W / Goddard, Julie A / Tjoa, Tjoson / Haidar, Yarah / Thomas, Carissa M

OTO open

2023 Volume 7, Issue 4, Page(s) e86

Abstract: Objective: To explore if antiplatelet or anticoagulant therapy increases the risk of transfusion requirement or postoperative hematoma formation in patients undergoing microvascular reconstruction for head and neck defects.: Study design: ... ...

Abstract	Objective: To explore if antiplatelet or anticoagulant therapy increases the risk of transfusion requirement or postoperative hematoma formation in patients undergoing microvascular reconstruction for head and neck defects. Study design: Retrospective cohort study. Setting: Departments of Otolaryngology-Head and Neck Surgery at the University of Alabama at Birmingham, the University of Colorado, and the University of California Irvine. Methods: A multi-institutional, retrospective review on microvascular reconstruction of the head and neck between August 2013 to July 2021. Perioperative antithrombotic data were collected to examine predictors of postoperative transfusion and hematoma. Results: A total of 843 free flaps were performed. Preoperative hemoglobin, hematocrit, operative time, and flap type were positive predictors of postoperative transfusion in both bivariate ( Conclusion: Antithrombotic regimens do not increase the risk of postoperative transfusion or hematoma in head and neck microvascular reconstruction. Based on this limited data, perioperative antithrombotic regimens can be considered in patients who may otherwise be at risk for these postoperative complications.
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Journal Article
ISSN	2473-974X
ISSN (online)	2473-974X
DOI	10.1002/oto2.86
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Article ; Online: Effect of Perioperative Antithrombotics on Head and Neck Microvascular Free Flap Survival After Anastomotic Revision.

Bishop, Jessica L / Vasudev, Milind / Garcia, Natalie / Heslop, Gabriela / Pham, Tiffany T / Hicks, Melanie D / Chowdhury, Farshad / Grayson, Jessica W / Goddard, Julie A / Tjoa, Tjoson / Haidar, Yarah / Thomas, Carissa M

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

2023 Volume 168, Issue 6, Page(s) 1353–1361

Abstract: Objective: To determine if antithrombotic therapy improves head and neck microvascular free flap survival following anastomotic revision.: Study design: A retrospective review of all patients with microvascular free tissue transfer to the head and ... ...

Abstract	Objective: To determine if antithrombotic therapy improves head and neck microvascular free flap survival following anastomotic revision. Study design: A retrospective review of all patients with microvascular free tissue transfer to the head and neck between August 2013 and July 2021. Setting: Otolaryngology-Head and Neck Surgery Departments at University of Alabama at Birmingham, University of Colorado, and University of California Irvine. Methods: Perioperative use of anticoagulation, antiplatelets, intraoperative heparin bolus, tissue plasminogen activator (tPA) and vasopressor use, and leech therapy were collected plus microvascular free flap outcomes. The primary endpoint was free flap failure. Analyses of free flaps that underwent anastomotic revision with or without thrombectomy were performed. Results: A total of 843 microvascular free flaps were included. The overall rate of flap failure was 4.0% (n = 34). The overall rate of pedicle anastomosis revision (artery, vein, or both) was 5.0% (n = 42) with a failure rate of 47.6% (n = 20) after revision. Anastomotic revision significantly increased the risk of flap failure (odds ratio [OR] 52.68, 95% confidence interval [CI] [23.90, 121.1], p < .0001) especially when both the artery and vein were revised (OR 9.425, 95% CI [2.117, 52.33], p = .005). Free flap failure after the anastomotic revision was not affected by postoperative antiplatelet therapy, postoperative prophylactic anticoagulation, intraoperative heparin bolus, tPA, and therapeutic anticoagulation regardless of which vessels were revised and if a thrombus was identified. Conclusion: In cases of microvascular free tissue transfer pedicle anastomotic revision, the use of antithrombotic therapy does not appear to significantly change free flap survival outcomes.
MeSH term(s)	Humans ; Free Tissue Flaps/blood supply ; Fibrinolytic Agents/therapeutic use ; Tissue Plasminogen Activator ; Heparin ; Postoperative Complications/prevention & control ; Retrospective Studies ; Anticoagulants/therapeutic use ; Anastomosis, Surgical ; Head and Neck Neoplasms/drug therapy
Chemical Substances	Fibrinolytic Agents ; Tissue Plasminogen Activator (EC 3.4.21.68) ; Heparin (9005-49-6) ; Anticoagulants
Language	English
Publishing date	2023-02-05
Publishing country	England
Document type	Journal Article
ZDB-ID	392085-9
ISSN	1097-6817 ; 0161-6439 ; 0194-5998
ISSN (online)	1097-6817
ISSN	0161-6439 ; 0194-5998
DOI	10.1002/ohn.295
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