Publications by authors named "Anthony Hall"

172 Publications

Chromosome-scale genome assembly provides insights into rye biology, evolution and agronomic potential.

Nat Genet 2021 04 18;53(4):564-573. Epub 2021 Mar 18.

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Seeland, Germany.

Rye (Secale cereale L.) is an exceptionally climate-resilient cereal crop, used extensively to produce improved wheat varieties via introgressive hybridization and possessing the entire repertoire of genes necessary to enable hybrid breeding. Rye is allogamous and only recently domesticated, thus giving cultivated ryes access to a diverse and exploitable wild gene pool. To further enhance the agronomic potential of rye, we produced a chromosome-scale annotated assembly of the 7.9-gigabase rye genome and extensively validated its quality by using a suite of molecular genetic resources. We demonstrate applications of this resource with a broad range of investigations. We present findings on cultivated rye's incomplete genetic isolation from wild relatives, mechanisms of genome structural evolution, pathogen resistance, low-temperature tolerance, fertility control systems for hybrid breeding and the yield benefits of rye-wheat introgressions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00807-0DOI Listing
April 2021

Orbital decompression.

Emerg Med Australas 2021 Mar 11. Epub 2021 Mar 11.

National Trauma Research Institute, Alfred Health, Melbourne, Victoria, Australia.

A trauma patient with orbital compartment syndrome may lose vision within hours of the injury. This article describes an approach to decompressing the orbit which may be sight-saving.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1742-6723.13768DOI Listing
March 2021

Uncovering candidate genes involved in photosynthetic capacity using unexplored genetic variation in Spring Wheat.

Plant Biotechnol J 2021 Feb 27. Epub 2021 Feb 27.

The Earlham Institute, Norwich, UK.

To feed an ever-increasing population we must leverage advances in genomics and phenotyping to harness the variation in wheat breeding populations for traits like photosynthetic capacity which remains unoptimized. Here we survey a diverse set of wheat germplasm containing elite, introgression and synthetic derivative lines uncovering previously uncharacterized variation. We demonstrate how strategic integration of exotic material alleviates the D genome genetic bottleneck in wheat, increasing SNP rate by 62% largely due to Ae. tauschii synthetic wheat donors. Across the panel, 67% of the Ae. tauschii donor genome is represented as introgressions in elite backgrounds. We show how observed genetic variation together with hyperspectral reflectance data can be used to identify candidate genes for traits relating to photosynthetic capacity using association analysis. This demonstrates the value of genomic methods in uncovering hidden variation in wheat and how that variation can assist breeding efforts and increase our understanding of complex traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pbi.13568DOI Listing
February 2021

Genital premalignant and malignant diseases: a retrospective study of male genital skin biopsies.

Int J Dermatol 2021 Feb 27. Epub 2021 Feb 27.

Mater Misericordiae Hospital, Brisbane, Queensland, Australia.

Background: Genital skin malignancies are a rare entity encountered by clinicians that may result in significant morbidity and mortality. Lack of familiarity or expertise in this area among clinicians can delay appropriate management of these conditions and may result in disease progression.

Methods: We performed a retrospective descriptive cohort study of male patients who received a genital skin biopsy reported by one major dermatopathology laboratory between January 2017 and December 2018 with a histological diagnosis of a premalignant or malignant condition. Patient age, type of clinician, clinical notes, genital site, type of biopsy performed, and histopathological diagnosis were evaluated.

Results: Of the 1525 male genital skin biopsies available for analysis, 5% (74/1525) were premalignant or malignant diseases. These included penile intraepithelial neoplasia (PeIN) (42/74, 57%), followed by invasive squamous cell carcinoma (SCC) (11/74, 15%), Bowenoid papulosis (BP) (9/74, 12%), basal cell carcinoma (8/74, 11%), malignant melanoma (2/74, 2.7%), extramammary Paget's (1/74, 1.4%), and metastatic cutaneous deposits (1/74, 1.4%). PeIN and BP most commonly affected the penile shaft ([18/42] 43% and [4/9] 44%, respectively), invasive SCCs most commonly affected the glans penis (4/11, 36%), and all BCCs (8/8, 100%) were located on the scrotum. Invasive SCCs were most biopsied by urologists, BP was most biopsied by dermatologists, and PeINs and BCCs were most biopsied by general practitioners.

Conclusions: A variety of genital malignancy types were found in males. A greater understanding of male genital premalignant and malignant conditions may help guide education and further research in this area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijd.15439DOI Listing
February 2021

Relative expression of putative genes involved in galanthamine and other Amaryllidaceae alkaloids biosynthesis in Narcissus field and in vitro tissues.

Gene 2021 Mar 9;774:145424. Epub 2021 Jan 9.

Honorary Senior Lecturer, Functional and Comparative Genomics, Institute of Integrative Biology, The Biosciences Building, Crown Street, The University of Liverpool, Liverpool L69 7ZB, United Kingdom. Electronic address:

The Narcissus pseudonarcissus cv. Carlton contains Amaryllidaceae alkaloids namely galanthamine, lycorine, homolycorine, narciclasine, which are noted for their pharmaceutical properties such as for the treatment of early to mid-stage Alzheimer's diseases, cancer, tumor etc. Alkaloid biosynthesis using plant in vitro systems has been considered as a tool for drug discovery and the pathways are starting to be understood but still far from complete. Therefore, the study was emphasized to observe the relative expressions of putative genes involved in the biosynthetic pathway leading to the Amaryllidaceae alkaloids in field grown bulbs and developing cell culture systems in Narcissus. MS media fortified with growth regulators were used for the development of tissue culture from Carlton twin-scale explants. MS medium with high auxin, 20 mg/l NAA was the best medium for callus growth and maintenance while media with low auxin, 4 mg/l NAA and MS basal media gave the maximum bulblets. Field tissues showed a higher amount of galanthamine content; i.e. basal plate (1050-1310 µg Gal/g FW) and bulb (980-1150 µg Gal/g FW) than the culture derived samples; callus (1.0-7.0 µg Gal/g FW) and bulblets (12-215 µg Gal/g FW) on a fresh weight (FW) basis. GC-MS chromatograms of samples under study also showed the presence of other important alkaloids i.e. lycorine, homolycorine, lycorenine, haemanthamine, crinamine, lycoramine and tazettine. RNA extracted from in vitro callus, bulblets and field grown bulb, basal plate were used for PCR to detect the relative expression of putative genes; P450, PAL, TYDC and NpOOMT normalized to actin. The selected transcripts for P450s and TYDC were expressed in both field and in vitro tissues. Higher expressions of PAL were observed in calli than field samples. The expression of NpN4OMT was notably higher in field samples than in vitro tissues. Therefore, in vitro tissues could be a good source for the reproducible and easy extraction of alkaloids from plants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2021.145424DOI Listing
March 2021

Recommendations for the management of childhood juvenile idiopathic arthritis-type chronic anterior uveitis.

Clin Exp Ophthalmol 2021 Jan 10;49(1):38-45. Epub 2021 Jan 10.

Save Sight Institute, The University of Sydney, Sydney, New South Wales, Australia.

Importance: Australian- and New Zealand-based, uveitis-specialized ophthalmologists have produced recommendations for the management of juvenile idiopathic arthritis (JIA)-type chronic anterior uveitis.

Background: Historically, the visual prognosis of JIA-type chronic anterior uveitis has been poor. New medical advances are likely to improve outcomes, but recently published guidelines are tailored for ophthalmic care in Europe and the United States.

Design: This work involved a consensus survey and a panel meeting.

Participants: The Australian and New Zealand JIA-Uveitis Working Group (29 ophthalmologists) participated in the work.

Methods: The Delphi technique was used to achieve consensus.

Main Outcome Measures: This work yielded consensus statements.

Results: The Working Group achieved consensus around 18 statements related to clinical evaluation, use of topical and regional corticosteroids, use of systemic corticosteroid and non-corticosteroid immunomodulatory drugs, and management of secondary cataract and glaucoma in childhood JIA-type uveitis.

Conclusions And Relevance: Recommendations of the Australian and New Zealand JIA-Uveitis Working Group provide current and regionally applicable advice for managing chronic anterior uveitis in children with JIA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ceo.13856DOI Listing
January 2021

Multiple wheat genomes reveal global variation in modern breeding.

Authors:
Sean Walkowiak Liangliang Gao Cecile Monat Georg Haberer Mulualem T Kassa Jemima Brinton Ricardo H Ramirez-Gonzalez Markus C Kolodziej Emily Delorean Dinushika Thambugala Valentyna Klymiuk Brook Byrns Heidrun Gundlach Venkat Bandi Jorge Nunez Siri Kirby Nilsen Catharine Aquino Axel Himmelbach Dario Copetti Tomohiro Ban Luca Venturini Michael Bevan Bernardo Clavijo Dal-Hoe Koo Jennifer Ens Krystalee Wiebe Amidou N'Diaye Allen K Fritz Carl Gutwin Anne Fiebig Christine Fosker Bin Xiao Fu Gonzalo Garcia Accinelli Keith A Gardner Nick Fradgley Juan Gutierrez-Gonzalez Gwyneth Halstead-Nussloch Masaomi Hatakeyama Chu Shin Koh Jasline Deek Alejandro C Costamagna Pierre Fobert Darren Heavens Hiroyuki Kanamori Kanako Kawaura Fuminori Kobayashi Ksenia Krasileva Tony Kuo Neil McKenzie Kazuki Murata Yusuke Nabeka Timothy Paape Sudharsan Padmarasu Lawrence Percival-Alwyn Sateesh Kagale Uwe Scholz Jun Sese Philomin Juliana Ravi Singh Rie Shimizu-Inatsugi David Swarbreck James Cockram Hikmet Budak Toshiaki Tameshige Tsuyoshi Tanaka Hiroyuki Tsuji Jonathan Wright Jianzhong Wu Burkhard Steuernagel Ian Small Sylvie Cloutier Gabriel Keeble-Gagnère Gary Muehlbauer Josquin Tibbets Shuhei Nasuda Joanna Melonek Pierre J Hucl Andrew G Sharpe Matthew Clark Erik Legg Arvind Bharti Peter Langridge Anthony Hall Cristobal Uauy Martin Mascher Simon G Krattinger Hirokazu Handa Kentaro K Shimizu Assaf Distelfeld Ken Chalmers Beat Keller Klaus F X Mayer Jesse Poland Nils Stein Curt A McCartney Manuel Spannagl Thomas Wicker Curtis J Pozniak

Nature 2020 12 25;588(7837):277-283. Epub 2020 Nov 25.

Crop Development Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Advances in genomics have expedited the improvement of several agriculturally important crops but similar efforts in wheat (Triticum spp.) have been more challenging. This is largely owing to the size and complexity of the wheat genome, and the lack of genome-assembly data for multiple wheat lines. Here we generated ten chromosome pseudomolecule and five scaffold assemblies of hexaploid wheat to explore the genomic diversity among wheat lines from global breeding programs. Comparative analysis revealed extensive structural rearrangements, introgressions from wild relatives and differences in gene content resulting from complex breeding histories aimed at improving adaptation to diverse environments, grain yield and quality, and resistance to stresses. We provide examples outlining the utility of these genomes, including a detailed multi-genome-derived nucleotide-binding leucine-rich repeat protein repertoire involved in disease resistance and the characterization of Sm1, a gene associated with insect resistance. These genome assemblies will provide a basis for functional gene discovery and breeding to deliver the next generation of modern wheat cultivars.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2961-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759465PMC
December 2020

Naturally occurring circadian rhythm variation associated with clock gene loci in Swedish Arabidopsis accessions.

Plant Cell Environ 2021 Mar 11;44(3):807-820. Epub 2021 Jan 11.

Organisms and Ecosystems, Earlham Institute, Norwich Research Park, Norwich, UK.

Circadian clocks have evolved to resonate with external day and night cycles. However, these entrainment signals are not consistent everywhere and vary with latitude, climate and seasonality. This leads to divergent selection for clocks which are locally adapted. To investigate the genetic basis for this circadian variation, we used a delayed fluorescence imaging assay to screen 191 naturally occurring Swedish Arabidopsis accessions for their circadian phenotypes. We demonstrate that the period length co-varies with both geography and population sub-structure. Several candidate loci linked to period, phase and relative amplitude error (RAE) were revealed by genome-wide association mapping and candidate genes were investigated using TDNA mutants. We show that natural variation in a single non-synonymous substitution within COR28 is associated with a long-period and late-flowering phenotype similar to that seen in TDNA knock-out mutants. COR28 is a known coordinator of flowering time, freezing tolerance and the circadian clock; all of which may form selective pressure gradients across Sweden. We demonstrate the effect of the COR28-58S SNP in increasing period length through a co-segregation analysis. Finally, we show that period phenotypic tails remain diverged under lower temperatures and follow a distinctive "arrow-shaped" trend indicative of selection for a cold-biased temperature compensation response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pce.13941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986795PMC
March 2021

Case Studies Discussing the Pathology, Immunogenicity, and Proposed Mechanism of Toxicity of an Inhaled Anti-TGFβ Humanized Fab Antibody in Non-Human Primates and Mice.

Toxicol Pathol 2021 Feb 10;49(2):315-333. Epub 2020 Nov 10.

70294Charles River Laboratories, Senneville, Quebec, Canada.

Treatment of nonhuman primates and mice with a humanized antigen-binding fragment (Fab) antibody (UCBFab) inhibiting transforming growth factor β via daily inhalation for up to 13 weeks resulted in low systemic exposure but high local exposure in the lung. Target engagement was demonstrated by reduced levels of signal transducers, phosphoSMAD and plasminogen activator inhibitor-1 in the bronchoalveolar lavage fluid (BALF). Treatment was associated with a high frequency and titer of antidrug antibodies, indicating high local immunogenicity, and local pathology within the lung and draining lymph nodes. Microscopic changes were characterized by perivascular (PV) and peribronchiolar (PB) mononuclear inflammatory cell (MIC) infiltrates that were principally lymphocytic in nature and mixed inflammatory cell infiltrates and/or inflammation within the alveoli. Immunohistochemical investigation revealed a predominantly CD68-positive macrophage and CD3- and CD8>CD4-positive T-cell response in the alveoli, whereas within the airways, there was a variable mixture of CD3-positive T cells, CD20-positive B cells, and CD68-positive macrophages. Increased cellularity of the draining lymph nodes was also noted, indicating the presence of an immune response to the inhaled test article. Morphologic changes did not progress over time, and all changes partially recovered. Increased leukocytes (principally macrophages) in BALF cytology correlated with the changes seen by histopathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0192623320960023DOI Listing
February 2021

Increased incidence of glaucoma medication usage in middle-aged Australian males taking antiretroviral medication - a population-based study.

J Ophthalmic Inflamm Infect 2020 Nov 3;10(1):30. Epub 2020 Nov 3.

Ophthalmology, The Alfred Hospital, Alfred Health, Melbourne, Australia.

Background: To investigate a possible association between glaucoma and the use of anti-retroviral therapy (ART) for HIV in the Australian population.

Methods: A retrospective review of Australian Pharmaceutical Benefits Scheme data was undertaken from July 2012 to December 2016, inclusive. Three patient groups were compared: those on both topical intraocular pressure (IOP) -lowering medication and ART, those on ART only, and those on IOP-lowering medication only, using the 2016 Australian resident population to estimate prevalence. Odds ratios (95% confidence intervals, [CI]) with Fishers exact test for p values were calculated stratified by age and gender.

Results: The number of prescriptions for topical glaucoma medications in the general Australian population increased progressively by age with a peak prevalence in those aged 80 years and above. Prevalence of ART was highest in males aged 40-49 and 50-59 years (0.41% [CI 0.40, 0.42] and 0.44% [CI 0.43, 0.45], respectively). Our analysis identified an increase in the prescription of IOP-lowering medication in males on ART aged 30-39 (OR 2.23 [CI 1.32, 3.75], p = 0.007) and 40-49 (OR 1.86 [CI 1.42, 2.43], p < 0.001), compared to those not on ART. There were no statistically significant increased odds for females or males aged 50 years or more.

Conclusion: Compared with the known increase in glaucoma prevalence with age in the general Australian population, a statistically significant increased prevalence in use of IOP-lowering medications was found in males on ART aged 30-49 years. The mechanism for this is yet to be determined, but possible causes include sequelae of HIV infection, a drug-induced side effect, or increased medical surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12348-020-00218-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609505PMC
November 2020

Medical and Surgical Treatment of Thyroid Eye Disease.

Intern Med J 2020 Sep 25. Epub 2020 Sep 25.

Department of Endocrinology & Diabetes, The Alfred, and Department of Medicine, Monash University Alfred Health, Melbourne, Australia, 3004.

Thyroid eye disease (TED) is an autoimmune inflammatory disease strongly associated with thyroid disease, principally Graves' disease. It can range from mild disease requiring observation or symptomatic treatments only, through to sight-threatening disease requiring major drug therapy and orbital surgery. Severity is graded by the NOSPECS system and activity by the Clinical Activity Score (CAS) to assist in treatment selection. Non-surgical management can extend from observation alone to minor therapy such as oral selenium, then glucocorticoid therapy, cyclosporin, mycophenolate, rituximab, immunoglobulin, teprotumumab, and orbital radiotherapy. High dose intravenous methylprednisolone therapy is used in active vision-threatening disease with early use of tarsorrhaphy and orbital decompression. Inactive but moderate to severe disease may be treated by orbital decompression, strabismus and eyelid surgery. Systematic assessment and management by both an endocrinologist and ophthalmologist to achieve and maintain euthyroidism and select and sequence treatments according to activity and severity of TED gives the best results for quality of life and vision. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imj.15067DOI Listing
September 2020

Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial.

Lancet Diabetes Endocrinol 2020 09 18;8(9):762-772. Epub 2020 Aug 18.

Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Background: Alkaptonuria is a rare, genetic, multisystem disease characterised by the accumulation of homogentisic acid (HGA). No HGA-lowering therapy has been approved to date. The aim of SONIA 2 was to investigate the efficacy and safety of once-daily nitisinone for reducing HGA excretion in patients with alkaptonuria and to evaluate whether nitisinone has a clinical benefit.

Methods: SONIA 2 was a 4-year, open-label, evaluator-blind, randomised, no treatment controlled, parallel-group study done at three sites in the UK, France, and Slovakia. Patients aged 25 years or older with confirmed alkaptonuria and any clinical disease manifestations were randomly assigned (1:1) to receive either oral nitisinone 10 mg daily or no treatment. Patients could not be masked to treatment due to colour changes in the urine, but the study was evaluator-blinded as far as possible. The primary endpoint was daily urinary HGA excretion (u-HGA) after 12 months. Clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) score was assessed at 12, 24, 36, and 48 months. Efficacy variables were analysed in all randomly assigned patients with a valid u-HGA measurement at baseline. Safety variables were analysed in all randomly assigned patients. The study was registered at ClinicalTrials.gov (NCT01916382).

Findings: Between May 7, 2014, and Feb 16, 2015, 139 patients were screened, of whom 138 were included in the study, with 69 patients randomly assigned to each group. 55 patients in the nitisinone group and 53 in the control group completed the study. u-HGA at 12 months was significantly decreased by 99·7% in the nitisinone group compared with the control group (adjusted geometric mean ratio of nitisinone/control 0·003 [95% CI 0·003 to 0·004], p<0·0001). At 48 months, the increase in cAKUSSI score from baseline was significantly lower in the nitisinone group compared with the control group (adjusted mean difference -8·6 points [-16·0 to -1·2], p=0·023). 400 adverse events occurred in 59 (86%) patients in the nitisinone group and 284 events occurred in 57 (83%) patients in the control group. No treatment-related deaths occurred.

Interpretation: Nitisinone 10 mg daily was well tolerated and effective in reducing urinary excretion of HGA. Nitisinone decreased ochronosis and improved clinical signs, indicating a slower disease progression.

Funding: European Commission Seventh Framework Programme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-8587(20)30228-XDOI Listing
September 2020

Reduced chromatin accessibility underlies gene expression differences in homologous chromosome arms of diploid Aegilops tauschii and hexaploid wheat.

Gigascience 2020 06;9(6)

Background: Polyploidy is centrally important in the evolution and domestication of plants because it leads to major genomic changes, such as altered patterns of gene expression, which are thought to underlie the emergence of new traits. Despite the common occurrence of these globally altered patterns of gene expression in polyploids, the mechanisms involved are not well understood.

Results: Using a precisely defined framework of highly conserved syntenic genes on hexaploid wheat chromosome 3DL and its progenitor 3 L chromosome arm of diploid Aegilops tauschii, we show that 70% of these gene pairs exhibited proportionately reduced gene expression, in which expression in the hexaploid context of the 3DL genes was ∼40% of the levels observed in diploid Ae tauschii. Several genes showed elevated expression during the later stages of grain development in wheat compared with Ae tauschii. Gene sequence and methylation differences probably accounted for only a few cases of differences in gene expression. In contrast, chromosome-wide patterns of reduced chromatin accessibility of genes in the hexaploid chromosome arm compared with its diploid progenitor were correlated with both reduced gene expression and the imposition of new patterns of gene expression.

Conclusions: Our pilot-scale analyses show that chromatin compaction may orchestrate reduced gene expression levels in the hexaploid chromosome arm of wheat compared to its diploid progenitor chromosome arm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gigascience/giaa070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305686PMC
June 2020

Wheat chromatin architecture is organized in genome territories and transcription factories.

Genome Biol 2020 04 29;21(1):104. Epub 2020 Apr 29.

Institute of Plant Sciences Paris of Saclay (IPS2), UMR 9213/UMR1403, CNRS, INRA, Orsay, France.

Background: Polyploidy is ubiquitous in eukaryotic plant and fungal lineages, and it leads to the co-existence of several copies of similar or related genomes in one nucleus. In plants, polyploidy is considered a major factor in successful domestication. However, polyploidy challenges chromosome folding architecture in the nucleus to establish functional structures.

Results: We examine the hexaploid wheat nuclear architecture by integrating RNA-seq, ChIP-seq, ATAC-seq, Hi-C, and Hi-ChIP data. Our results highlight the presence of three levels of large-scale spatial organization: the arrangement into genome territories, the diametrical separation between facultative and constitutive heterochromatin, and the organization of RNA polymerase II around transcription factories. We demonstrate the micro-compartmentalization of transcriptionally active genes determined by physical interactions between genes with specific euchromatic histone modifications. Both intra- and interchromosomal RNA polymerase-associated contacts involve multiple genes displaying similar expression levels.

Conclusions: Our results provide new insights into the physical chromosome organization of a polyploid genome, as well as on the relationship between epigenetic marks and chromosome conformation to determine a 3D spatial organization of gene expression, a key factor governing gene transcription in polyploids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-020-01998-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189446PMC
April 2020

A framework for gene mapping in wheat demonstrated using the Yr7 yellow rust resistance gene.

PLoS One 2020 15;15(4):e0231157. Epub 2020 Apr 15.

School of Agriculture, Policy and Development, University of Reading, Reading, England, United Kingdom.

We used three approaches to map the yellow rust resistance gene Yr7 and identify associated SNPs in wheat. First, we used a traditional QTL mapping approach using a double haploid (DH) population and mapped Yr7 to a low-recombination region of chromosome 2B. To fine map the QTL, we then used an association mapping panel. Both populations were SNP array genotyped allowing alignment of QTL and genome-wide association scans based on common segregating SNPs. Analysis of the association panel spanning the QTL interval, narrowed the interval down to a single haplotype block. Finally, we used mapping-by-sequencing of resistant and susceptible DH bulks to identify a candidate gene in the interval showing high homology to a previously suggested Yr7 candidate and to populate the Yr7 interval with a higher density of polymorphisms. We highlight the power of combining mapping-by-sequencing, delivering a complete list of gene-based segregating polymorphisms in the interval with the high recombination, low LD precision of the association mapping panel. Our mapping-by-sequencing methodology is applicable to any trait and our results validate the approach in wheat, where with a near complete reference genome sequence, we are able to define a small interval containing the causative gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159211PMC
July 2020

Genetic susceptibility to hydroxychloroquine retinal toxicity.

Ophthalmic Genet 2020 04 13;41(2):159-170. Epub 2020 Apr 13.

Department of Surgery, Central Clinical School, Monash University, Melbourne, Australia.

Hydroxychloroquine retinal toxicity can occur in up to 7.5% of patients receiving treatment; however, possible genetic risk factors are poorly understood. The main objective of the study was to explore candidate genetic risk factors for retinal toxicity. Case-control study of patients with confirmed hydroxychloroquine retinal toxicity identified through ophthalmology departments of tertiary care hospitals and private ophthalmic practice in Australia. Participants were 26 Caucasian patients with hydroxychloroquine retinal toxicity who were matched with control subjects for age, gender, treatment duration and indication for hydroxychloroquine treatment. Participants underwent clinical examination, optical coherence tomographic scanning, automated field testing and whole exome sequencing of DNA extracted from saliva or blood. Outcome measures were grade of hydroxychloroquine toxicity and mutations in a panel of 40 candidate genes. No susceptibility or protective factors were identified in either the cohort as a whole or any subset of patients. Further larger studies, with whole-exome analysis and consideration of additional modifying genes are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13816810.2020.1747093DOI Listing
April 2020

Epidemiology of episcleritis and scleritis in urban Australia.

Clin Exp Ophthalmol 2020 08 3;48(6):757-766. Epub 2020 May 3.

Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.

Importance: The epidemiology of episcleritis and scleritis in Australia is largely unknown.

Background: To determine the incidence, prevalence and clinical characteristics of episcleritis and scleritis in Melbourne.

Design: Retrospective longitudinal study.

Participants: Patients aged ≥18 years with episcleritis or scleritis seen at the Royal Victorian Eye and Ear Hospital from November 2014 to October 2015.

Methods: Medical record review confirmed clinical diagnosis and characteristics. Incidence and prevalence were calculated using estimates of the adult population in areas of Melbourne with ≥30 ocular presentations/year to the emergency department.

Main Outcome Measures: Diagnosis of active episcleritis or scleritis, aetiology, ocular complications and treatments.

Results: From a general population of 3 408 068, we confirmed 149 new and 23 pre-existing cases of active episcleritis, and 35 new and 23 pre-existing cases of active scleritis. Incidence per 100 000 person-years was 4.4 (95% confidence interval [CI] 3.7-5.1) for episcleritis and 1.0 (95% CI 0.7-1.4) for scleritis, while 12-month prevalence was 5.1 (95% CI 4.3-5.9) and 1.7 (1.3-2.2) per 100 000 persons, respectively. Systemic disease was associated with 10% of episcleritis compared with 34% of scleritis (P < .001). Ocular complications were seen in 3% (6/184) of episcleritis eyes and 44% (32/72) of scleritis eyes, with the commonest being anterior uveitis (12/72) and ocular hypertension (14/72). At presentation, scleritis patients were commonly treated with oral non-steroidal anti-inflammatory drugs (60%) and prednisolone (19%). By 12 months, 24% of scleritis patients required immunosuppressants.

Conclusions And Relevance: Rates of episcleritis and scleritis in our single-centre Australian study were low. Episcleritis was usually benign, whereas scleritis had increased ocular complications and systemic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ceo.13761DOI Listing
August 2020

Vitamin D and Ocular Inflammation.

Ocul Immunol Inflamm 2020 04;28(3):337-340

Centre for Ophthalmology, University Tuebingen, Tuebingen, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09273948.2020.1734421DOI Listing
April 2020

Portion-controlled spinach for improved vitamin K antagonist anticoagulant control.

Br J Haematol 2020 05 3;189(3):e71-e73. Epub 2020 Feb 3.

Nutristasis Unit, Viapath, St. Thomas' Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.16481DOI Listing
May 2020

Nanopore direct RNA sequencing maps the complexity of Arabidopsis mRNA processing and mA modification.

Elife 2020 01 14;9. Epub 2020 Jan 14.

School of Life Sciences, University of Dundee, Dundee, United Kingdom.

Understanding genome organization and gene regulation requires insight into RNA transcription, processing and modification. We adapted nanopore direct RNA sequencing to examine RNA from a wild-type accession of the model plant and a mutant defective in mRNA methylation (mA). Here we show that mA can be mapped in full-length mRNAs transcriptome-wide and reveal the combinatorial diversity of cap-associated transcription start sites, splicing events, poly(A) site choice and poly(A) tail length. Loss of mA from 3' untranslated regions is associated with decreased relative transcript abundance and defective RNA 3' end formation. A functional consequence of disrupted mA is a lengthening of the circadian period. We conclude that nanopore direct RNA sequencing can reveal the complexity of mRNA processing and modification in full-length single molecule reads. These findings can refine Arabidopsis genome annotation. Further, applying this approach to less well-studied species could transform our understanding of what their genomes encode.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.49658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959997PMC
January 2020

HR-pQCT Measures of Bone Microarchitecture Predict Fracture: Systematic Review and Meta-Analysis.

J Bone Miner Res 2020 03 19;35(3):446-459. Epub 2019 Nov 19.

Research Center, Shriners Hospital for Children, Montreal, Canada.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (1) assess fracture-associated differences in HR-pQCT bone parameters; and (2) to determine if HR-pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR-pQCT (39/40 used XtremeCT scanners) to assess 1291 to 3253 and 3389 to 10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta-analysis. An additional meta-analysis of short-term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture-associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR-pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from -2.6% (95% confidence interval [CI] -3.4 to -1.9) in radial cortical vBMD to -12.6% (95% CI -15.0 to -10.3) in radial trabecular vBMD. Fracture-associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR-pQCT can predict incident fracture. Assessment of study quality, heterogeneity, and publication biases verified the validity of these findings. Finally, we demonstrated that fracture-associated deficits in total and trabecular vBMD and certain tibial cortical parameters can be reliably discerned from HR-pQCT-related precision error and can be used to detect fracture-associated differences in individual patients. Although differences in other HR-pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross-sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR-pQCT in clinical fracture prediction. © 2019 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3901DOI Listing
March 2020

Patterns of Vitamin D Levels and Exposures in Active and Inactive Noninfectious Uveitis Patients.

Ophthalmology 2020 02 11;127(2):230-237. Epub 2019 Jul 11.

Department of Surgery, Monash Medical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia; Department of Ophthalmology, The Alfred Hospital, Melbourne, Australia. Electronic address:

Purpose: To compare serum vitamin D levels and patterns of ultraviolet light and dietary exposure among patients with active and inactive noninfectious uveitis and population controls.

Design: Prospective case-control study. All participants (n = 151) underwent serum 25-hydroxy vitamin D measurement and completed a questionnaire on vitamin D intake and ultraviolet light exposure. Serum 25-hydroxy vitamin D levels were compared between active and inactive uveitis groups and with local population estimates.

Participants: Adult patients with active and inactive noninfectious uveitis were recruited from 2 Victorian tertiary hospitals and 1 private ophthalmic practice.

Methods: Serum 25-hydroxy vitamin D levels were compared between patients with active and inactive uveitis and population-based estimates of serum 25-hydroxy vitamin D levels, stratified by geographic region and season. Vitamin D intakes and exposures based on questionnaire results, including vitamin D supplementation and sunlight exposures on weekdays and weekends, were compared between active and inactive uveitis groups.

Main Outcome Measures: Serum vitamin D levels, intake of vitamin D, and exposure to sources of vitamin D.

Results: The median level of serum vitamin D in those with active uveitis (n = 74) was 46 nmol/l (interquartile range [IQR], 29-70 nmol/l), significantly lower than in the inactive control group (n = 77) at 64 nmol/l (IQR, 52-79 nmol/l; P < 0.001). The active uveitis group also showed lower median serum vitamin D levels than the local population median of 62 nmol/l (IQR, 46-77 nmol/l). Vitamin D supplementation also was associated significantly with uveitis inactivity (P = 0.026, Kendall's τ test). In a subanalysis of vitamin D-deficient participants, sun exposure was associated significantly with uveitis inactivity (P = 0.014 for weekday and weekend analyses).

Conclusions: Participants with active uveitis showed significantly lower serum 25-hydroxy vitamin D levels than inactive uveitis patients and local population-based estimates. Vitamin D supplementation was found to be associated with decreased uveitis activity, as was sun exposure in those with vitamin D deficiency. These results suggest that vitamin D supplementation should be studied as an option for the prevention of uveitis relapse in at-risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2019.06.030DOI Listing
February 2020

Ordered Intermetallic PdBi Prepared by an Electrochemically Induced Phase Transformation for Oxygen Reduction Electrocatalysis.

ACS Nano 2019 Sep 5;13(9):10818-10825. Epub 2019 Sep 5.

Department of Materials Science and Engineering , Johns Hopkins University , Baltimore , Maryland 21218 , United States.

The synthesis of alloys with long-range atomic-scale ordering (ordered intermetallics) is an emerging field of nanochemistry. Ordered intermetallic nanoparticles are useful for a wide variety of applications such as catalysis, superconductors, and magnetic devices. However, the preparation of nanostructured ordered intermetallics is challenging in comparison to disordered alloys, hindering progress in material development. Herein, we report a process for converting colloidally synthesized ordered intermetallic PdBi to ordered intermetallic PdBi nanoparticles under ambient conditions by electrochemical dealloying. The low melting point of PdBi corresponds to low vacancy formation energies, which enables the facile removal of the Bi from the surface while simultaneously enabling interdiffusion of the constituent atoms via a vacancy diffusion mechanism under ambient conditions. The resulting phase-converted ordered intermetallic PdBi exhibits 11 times and 3.5 times higher mass activity and high methanol tolerance for the oxygen reduction reaction compared with Pt/C and Pd/C, respectively, which is the highest reported for a Pd-based catalyst, to the best of our knowledge. These results establish a key development in the synthesis of noble-metal-rich ordered intermetallic phases with high catalytic activity and set forth guidelines for the design of ordered intermetallic compounds under ambient conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.9b06019DOI Listing
September 2019

Coordinated circadian timing through the integration of local inputs in Arabidopsis thaliana.

PLoS Biol 2019 08 15;17(8):e3000407. Epub 2019 Aug 15.

Sainsbury Laboratory, University of Cambridge, Cambridge, United Kingdom.

Individual plant cells have a genetic circuit, the circadian clock, that times key processes to the day-night cycle. These clocks are aligned to the day-night cycle by multiple environmental signals that vary across the plant. How does the plant integrate clock rhythms, both within and between organs, to ensure coordinated timing? To address this question, we examined the clock at the sub-tissue level across Arabidopsis thaliana seedlings under multiple environmental conditions and genetic backgrounds. Our results show that the clock runs at different speeds (periods) in each organ, which causes the clock to peak at different times across the plant in both constant environmental conditions and light-dark (LD) cycles. Closer examination reveals that spatial waves of clock gene expression propagate both within and between organs. Using a combination of modeling and experiment, we reveal that these spatial waves are the result of the period differences between organs and local coupling, rather than long-distance signaling. With further experiments we show that the endogenous period differences, and thus the spatial waves, can be generated by the organ specificity of inputs into the clock. We demonstrate this by modulating periods using light and metabolic signals, as well as with genetic perturbations. Our results reveal that plant clocks can be set locally by organ-specific inputs but coordinated globally via spatial waves of clock gene expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.3000407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695092PMC
August 2019

A high-throughput delayed fluorescence method reveals underlying differences in the control of circadian rhythms in and .

Plant Methods 2019 21;15:51. Epub 2019 May 21.

1Earlham Institute, Norwich Research Park, Norwich, NR4 7UG UK.

Background: A robust circadian clock has been implicated in plant resilience, resource-use efficiency, competitive growth and yield. A huge number of physiological processes are under circadian control in plants including: responses to biotic and abiotic stresses; flowering time; plant metabolism; and mineral uptake. Understanding how the clock functions in crops such as (bread wheat) and (oilseed rape) therefore has great agricultural potential. Delayed fluorescence (DF) imaging has been shown to be applicable to a wide range of plant species and requires no genetic transformation. Although DF has been used to measure period length of both mutants and wild ecotypes of , this assay has never been systematically optimised for crop plants. The physical size of both and led us to develop a representative sampling strategy which enables high-throughput imaging of these crops.

Results: In this study, we describe the plant-specific optimisation of DF imaging to obtain reliable circadian phenotypes with the robustness and reproducibility to detect diverging periods between cultivars of the same species. We find that the age of plant material, light regime and temperature conditions all significantly effect DF rhythms and describe the optimal conditions for measuring robust rhythms in each species. We also show that sections of leaf can be used to obtain period estimates with improved throughput for larger sample size experiments.

Conclusions: We present an optimized protocol for high-throughput phenotyping of circadian period specific to two economically valuable crop plants. Application of this method revealed significant differences between the periods of several widely grown elite cultivars. This method also identified intriguing differential responses of circadian rhythms in compared to ; specifically the dramatic change to rhythm robustness when plants were imaged under constant light versus constant darkness. This points towards diverging networks underlying circadian control in these two species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13007-019-0436-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530173PMC
May 2019

Differences in practice of ophthalmology by gender in Australia.

Clin Exp Ophthalmol 2019 Sep 16;47(7):840-846. Epub 2019 May 16.

Ophthalmology, The Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.

Importance: The number of females practising ophthalmology is rising. It is known that practice patterns between female and male ophthalmologists differ. Understanding the differences will help to inform future workforce planning.

Background: To investigate the differences in clinical practice between female and male ophthalmologists in Australia.

Design: Cross-sectional study.

Participants: Ophthalmologists participating in the Royal Australian & New Zealand College of Ophthalmologists workforce survey, and/or Medicine in Australia: Balancing Employment and Life survey, and those who made claims from Medicare Benefits Schedule Australia.

Methods: Combined analysis of de-identified 2014 data from the surveys and Medicare Benefits Schedule.

Main Outcome Measures: Hours worked, service provision, remuneration and social circumstances.

Results: Female ophthalmologists provided 35% fewer services per ophthalmologist per year (2834 vs 4328) than male ophthalmologists. Female ophthalmologists received approximately half the annual income of male ophthalmologists; median self-reported net personal annual income was AUD122 500 (interquartile range [IQR] 96 000-225 000) for females compared to AUD245 000 (IQR 180 000-365 000) for males (P = .01). The median self-reported hours worked per week was 35.0 (IQR 28.0-46.0) for females and 41.8 (IQR 36.5-48.5) for males (P = 0.04). A higher proportion of females practise in medical subspecialties, while a higher proportion of males practise in surgical subspecialties.

Conclusions And Relevance: Female ophthalmologists earn less compared to male ophthalmologists after accounting for lower service provision and hours worked. Difference in income may be partially accounted for by higher total number of services and procedural services provided by male ophthalmologists. Understanding differences between female and male ophthalmologists will help to inform future medical workforce planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ceo.13523DOI Listing
September 2019

Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency.

Genome Biol 2019 04 15;20(1):69. Epub 2019 Apr 15.

Earlham Institute, Norwich, NR4 7UZ, UK.

Background: Sequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. A lack of recombination limits breeding efforts in crops; therefore, increasing recombination rates can reduce linkage drag and generate new genetic combinations.

Results: We use computational analysis of 13 recombinant inbred mapping populations to assess crossover and gene conversion frequency in the hexaploid genome of wheat (Triticum aestivum). We observe that high-frequency crossover sites are shared between populations and that closely related parents lead to populations with more similar crossover patterns. We demonstrate that gene conversion is more prevalent and covers more of the genome in wheat than in other plants, making it a critical process in the generation of new haplotypes, particularly in centromeric regions where crossovers are rare. We identify quantitative trait loci for altered gene conversion and crossover frequency and confirm functionality for a novel RecQ helicase gene that belongs to an ancient clade that is missing in some plant lineages including Arabidopsis.

Conclusions: This is the first gene to be demonstrated to be involved in gene conversion in wheat. Harnessing the RecQ helicase has the potential to break linkage drag utilizing widespread gene conversions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-019-1675-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463664PMC
April 2019

Integrating genomic resources to present full gene and putative promoter capture probe sets for bread wheat.

Gigascience 2019 04;8(4)

Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK.

Background: Whole-genome shotgun resequencing of wheat is expensive because of its large, repetitive genome. Moreover, sequence data can fail to map uniquely to the reference genome, making it difficult to unambiguously assign variation. Resequencing using target capture enables sequencing of large numbers of individuals at high coverage to reliably identify variants associated with important agronomic traits. Previous studies have implemented complementary DNA/exon or gene-based probe sets in which the promoter and intron sequence is largely missing alongside newly characterized genes from the recent improved reference sequences.

Results: We present and validate 2 gold standard capture probe sets for hexaploid bread wheat, a gene and a putative promoter capture, which are designed using recently developed genome sequence and annotation resources. The captures can be combined or used independently. We demonstrate that the capture probe sets effectively enrich the high-confidence genes and putative promoter regions that were identified in the genome alongside a large proportion of the low-confidence genes and associated promoters. Finally, we demonstrate successful sample multiplexing that allows generation of adequate sequence coverage for single-nucleotide polymorphism calling while significantly reducing cost per sample for gene and putative promoter capture.

Conclusions: We show that a capture design employing an "island strategy" can enable analysis of the large gene/putative promoter space of wheat with only 2 × 160 Mbp probe sets. Furthermore, these assays extend the regions of the wheat genome that are amenable to analyses beyond its exome, providing tools for detailed characterization of these regulatory regions in large populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gigascience/giz018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461119PMC
April 2019

Rapid Room-Temperature Synthesis of a Metastable Ordered Intermetallic Electrocatalyst.

J Am Chem Soc 2019 Feb 1;141(6):2342-2347. Epub 2019 Feb 1.

Department of Materials Science and Engineering , Johns Hopkins University , Baltimore , Maryland 21218 , United States.

Metal alloys with atomic scale ordering (ordered intermetallics) have emerged as a new class of high performance materials for mediating electrochemical reactions. However, ordered intermetallic nanostructures often require long synthesis times and/or high temperature annealing to form because a high-activation energy barrier for interdiffusion must be overcome for the constituent metals to equilibrate into ordered structures. Here we report the direct synthesis of metastable ordered intermetallic PdBi at room-temperature in minutes via electrochemical deposition. PdBi is highly active for the reduction of O to HO, delivering specific activities over 35× higher than those of commercial Pt and Pd nanocatalysts, placing it as the most active Pd-based catalyst, to the best of our knowledge, reported under similar testing conditions. Stability tests demonstrate minimal loss of activity after 10,000 cycles, and a retention of intermetallic crystallinity. This study demonstrates a new method of preparing ordered intermetallics with extraordinary catalytic activity at room temperature, providing a new direction in catalyst discovery and synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.8b09919DOI Listing
February 2019