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Article ; Online: Culturing and Mating of Aspergillus fumigatus.

Ashton, George D / Dyer, Paul S

2019 Volume 54, Issue 1, Page(s) e87

Abstract: Aspergillus fumigatus is an opportunistic human fungal pathogen, capable of causing invasive aspergillosis in patients with compromised immune systems. The fungus was long considered a purely asexual organism. However, a sexual cycle was reported in 2009, ...

Abstract	Aspergillus fumigatus is an opportunistic human fungal pathogen, capable of causing invasive aspergillosis in patients with compromised immune systems. The fungus was long considered a purely asexual organism. However, a sexual cycle was reported in 2009, with methods described to induce mating under laboratory conditions. The presence of a sexual cycle now offers a valuable tool for classical genetic analysis of the fungus, such as allowing determination of whether traits of interest are mono- or poly-genic in nature. For example, the sexual cycle is currently being exploited to determine the genetic basis of traits of medical importance such as resistance to azole antifungals and virulence, and to characterize the genes involved. The sexual cycle can also be used to assess the possibility of gene flow between isolates. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This unit describes protocols for culturing of A. fumigatus and for inducing sexual reproduction between compatible MAT1-1 and MAT1-2 isolates of the species. The unit also provides working methods for harvesting sexual structures, isolating single-spore progeny and confirming whether sexual recombination has occurred. © The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
MeSH term(s)	Aspergillosis/microbiology ; Aspergillus fumigatus/genetics ; Aspergillus fumigatus/growth & development ; Aspergillus fumigatus/physiology ; Culture Media/chemistry ; Culture Media/metabolism ; Genes, Mating Type, Fungal ; Humans ; Mycology/instrumentation ; Mycology/methods ; Polymerase Chain Reaction/methods ; Preservation, Biological/methods ; Spores, Fungal/genetics ; Spores, Fungal/growth & development ; Spores, Fungal/physiology
Chemical Substances	Culture Media
Language	English
Publishing date	2019-09-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2213675-7
ISSN	1934-8533 ; 1934-8525
ISSN (online)	1934-8533
ISSN	1934-8525
DOI	10.1002/cpmc.87
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Article ; Online: Zinc and its role in vitamin D function

Ashton Amos / Mohammed S. Razzaque

Current Research in Physiology, Vol 5, Iss , Pp 203-

2022 Volume 207

Abstract: Zinc is an essential mineral with an important relationship with vitamin D. Studies have found ... that reduced blood zinc levels could predict vitamin D deficiency in adolescent girls, while zinc ... supplementation increased vitamin D levels in postmenopausal women. In vitro studies using human ...

Abstract	Zinc is an essential mineral with an important relationship with vitamin D. Studies have found that reduced blood zinc levels could predict vitamin D deficiency in adolescent girls, while zinc supplementation increased vitamin D levels in postmenopausal women. In vitro studies using human peritoneal macrophages have found that zinc induced the release of calcitriol (1,25-dihydroxycholecalciferol). Zinc also acts as a cofactor for vitamin D functions, as the transcriptional activity of vitamin D-dependent genes relies on zinc to exert pleiotropic functions, including mineral ion regulation. Vitamin D could also induce zinc transporters to regulate zinc homeostasis. Together, zinc and vitamin D in adequate concentrations help maintain a healthy musculoskeletal system and beyond; however, deficiency in either of these nutrients can result in various disorders affecting almost all body systems. This brief article will focus on the role of zinc in vitamin D functions.
Keywords	Zinc ; Vitamin D ; Sources ; Interactions ; Deficiency ; Physiology ; QP1-981 ; Specialties of internal medicine ; RC581-951
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Enhancing the repeatability and sensitivity of low-cost PCB, pH-sensitive field-effect transistors.

Ashton, Rhys / Silver, Callum D / Bird, Toby W / Coulson, Ben / Pratt, Andrew / Johnson, Steven

Biosensors & bioelectronics

2023 Volume 227, Page(s) 115150

Abstract: Discrete, extended gate pH-sensitive field-effect transistors (dEGFETs) fabricated on printed circuit boards (PCBs) are a low-cost, simple to manufacture analytical technology that can be applied to a wide range of applications. Electrodeposited iridium ... ...

Abstract	Discrete, extended gate pH-sensitive field-effect transistors (dEGFETs) fabricated on printed circuit boards (PCBs) are a low-cost, simple to manufacture analytical technology that can be applied to a wide range of applications. Electrodeposited iridium oxide (IrOx) films have emerged as promising pH-sensitive layers owing to their theoretically high pH sensitivity and facile deposition, but typically exhibit low pH sensitivity or lack reproducibility. Moreover, to date, a combined IrOx and dEGFET PCB system has not yet been realised. In this study, we demonstrate a dEGFET pH sensor based on an extended gate manufactured on PCB that is rendered pH sensitive through an electrodeposited IrOx film, which can reliably and repeatably display beyond-Nernstian pH response. Using a combination of complementary surface analysis techniques, we show that the high pH sensitivity and repeatability of the dEGFETs are dependent on both the chemical composition and critically the uniformity of the IrOx film. The IrOx film uniformity can be enhanced through electrochemical polishing of the extended gate electrode prior to electrodeposition, leading to dEGFETs that exhibit a median pH sensitivity of 70.7 ± 5 mV/pH (n = 56) compared to only 31.3 ± 14 mV/pH (n = 31) for IrOx electrodeposited on non-polished PCB electrodes. Finally, we demonstrate the applicability of these devices by demonstrating the detection and quantification of ampicillin due to β-Lactamase enzyme activity, thus laying the foundation for cheap and ubiquitous sensors which can be applied to a range of global challenges across healthcare and environmental monitoring.
MeSH term(s)	Reproducibility of Results ; Biosensing Techniques/methods ; Electrodes ; Hydrogen-Ion Concentration
Language	English
Publishing date	2023-02-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2023.115150
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Article ; Online: The physiologic benefits of optimizing cardiorespiratory fitness and physical activity - From the cell to systems level in a post-pandemic world.

Faghy, Mark A / Tatler, Amanda / Chidley, Corinna / Fryer, Simon / Stoner, Lee / Laddu, Deepika / Arena, Ross / Ashton, Ruth E

Progress in cardiovascular diseases

2024 Volume 83, Page(s) 49–54

Abstract: Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates ... ...

Abstract	Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates clear associations between physical activity (PA) and cardiorespiratory fitness (CRF) which can offset the risk of mortality and increase life expectancy and the quality of life in patients. Whilst well documented, the narrative of increased CRF remained pertinent during the coronavirus disease 2019 (COVID-19) pandemic, where individuals with lower levels of CRF had more than double the risk of dying from COVID-19 compared to those with a moderate or high CRF. The need to better understand the mechanisms associated with COVID-19 and those that continue to be affected with persistent symptoms following infection (Long COVID), and CV health is key if we are to be able to effectively target the use of CRF and PA to improve the lives of those suffering its afflictions. Whilst there is a long way to go to optimise PA and CRF for improved health at a population level, particularly in a post-pandemic world, increasing the understanding using a cellular-to-systems approach, we hope to provide further insight into the benefits of engaging in PA.
MeSH term(s)	Humans ; Cardiorespiratory Fitness ; COVID-19/epidemiology ; Exercise/physiology ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/physiopathology ; Cardiovascular Diseases/prevention & control ; SARS-CoV-2 ; Quality of Life
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	209312-1
ISSN	1873-1740 ; 1532-8643 ; 0033-0620
ISSN (online)	1873-1740 ; 1532-8643
ISSN	0033-0620
DOI	10.1016/j.pcad.2024.02.006
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Article: Longitudinal progression of blood biomarkers reveals a key role of astrocyte reactivity in preclinical Alzheimer's disease.

Varma, V R / An, Y / Kac, P R / Bilgel, M / Moghekar, A / Loeffler, T / Amschl, D / Troncoso, J / Blennow, K / Zetterberg, H / Ashton, N J / Resnick, S M / Thambisetty, M

medRxiv : the preprint server for health sciences

2024

Abstract: Defining the progression of blood biomarkers of Alzheimer's disease (AD) is essential for targeting treatments in patients most likely to benefit from early intervention. We delineated the temporal ordering of blood biomarkers a decade prior to the onset ...

Abstract	Defining the progression of blood biomarkers of Alzheimer's disease (AD) is essential for targeting treatments in patients most likely to benefit from early intervention. We delineated the temporal ordering of blood biomarkers a decade prior to the onset of AD symptoms in participants in the Baltimore Longitudinal Study of Aging. We show that increased astrocyte reactivity, assessed by elevated glial fibrillary acidic protein (GFAP) levels is an early event in the progression of blood biomarker changes in preclinical AD. In AD-converters who are initially cognitively unimpaired (N=158, 377 serial plasma samples), higher plasma GFAP levels are observed as early as 10-years prior to the onset of cognitive impairment due to incident AD compared to individuals who remain cognitively unimpaired (CU, N=160, 379 serial plasma samples). Plasma GFAP levels in AD-converters remain elevated 5-years prior to and coincident with the onset of cognitive impairment due to AD. In participants with neuropathologically confirmed AD, plasma GFAP levels are elevated relative to cognitively normal individuals and intermediate in those who remain cognitively unimpaired despite significant AD pathology (asymptomatic AD). Higher plasma GFAP levels at death are associated with greater severity of both neuritic plaques and neurofibrillary tangles. In the 5XFAD transgenic model of AD, we observed greater GFAP levels in the cortex and hippocampus of transgenic mice relative to wild-type prior to the development of cognitive impairment. Reactive astrocytosis, an established biological response to neuronal injury, may be an early initiator of AD pathogenesis and a promising therapeutic target.
Language	English
Publishing date	2024-01-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.25.24301779
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Article ; Online: Expression of the wheat multipathogen resistance hexose transporter Lr67res is associated with anion fluxes.

Milne, Ricky J / Dibley, Katherine E / Bose, Jayakumar / Ashton, Anthony R / Ryan, Peter R / Tyerman, Stephen D / Lagudah, Evans S

Plant physiology

2023 Volume 192, Issue 2, Page(s) 1254–1267

Abstract: Many disease resistance genes in wheat (Triticum aestivum L.) confer strong resistance to specific pathogen races or strains, and only a small number of genes confer multipathogen resistance. The Leaf rust resistance 67 (Lr67) gene fits into the latter ... ...

Abstract	Many disease resistance genes in wheat (Triticum aestivum L.) confer strong resistance to specific pathogen races or strains, and only a small number of genes confer multipathogen resistance. The Leaf rust resistance 67 (Lr67) gene fits into the latter category as it confers partial resistance to multiple biotrophic fungal pathogens in wheat and encodes a Sugar Transport Protein 13 (STP13) family hexose-proton symporter variant. Two mutations (G144R, V387L) in the resistant variant, Lr67res, differentiate it from the susceptible Lr67sus variant. The molecular function of the Lr67res protein is not understood, and this study aimed to broaden our knowledge on this topic. Biophysical analysis of the wheat Lr67sus and Lr67res protein variants was performed using Xenopus laevis oocytes as a heterologous expression system. Oocytes injected with Lr67sus displayed properties typically associated with proton-coupled sugar transport proteins-glucose-dependent inward currents, a Km of 110 ± 10 µM glucose, and a substrate selectivity permitting the transport of pentoses and hexoses. By contrast, Lr67res induced much larger sugar-independent inward currents in oocytes, implicating an alternative function. Since Lr67res is a mutated hexose-proton symporter, the possibility of protons underlying these currents was investigated but rejected. Instead, currents in Lr67res oocytes appeared to be dominated by anions. This conclusion was supported by electrophysiology and 36Cl- uptake studies and the similarities with oocytes expressing the known chloride channel from Torpedo marmorata, TmClC-0. This study provides insights into the function of an important disease resistance gene in wheat, which can be used to determine how this gene variant underpins disease resistance in planta.
MeSH term(s)	Disease Resistance/genetics ; Triticum/metabolism ; Chlorine/metabolism ; Radioisotopes/metabolism ; Monosaccharide Transport Proteins/genetics ; Protons ; Oocytes/metabolism ; Hexoses/metabolism ; Glucose ; Sugars ; Plant Diseases/genetics ; Plant Diseases/microbiology
Chemical Substances	Chlorine-36 ; Chlorine (4R7X1O2820) ; Radioisotopes ; Monosaccharide Transport Proteins ; Protons ; Hexoses ; Glucose (IY9XDZ35W2) ; Sugars
Language	English
Publishing date	2023-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208914-2
ISSN	1532-2548 ; 0032-0889
ISSN (online)	1532-2548
ISSN	0032-0889
DOI	10.1093/plphys/kiad104
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Article ; Online: Zinc and its role in vitamin D function.

Amos, Ashton / Razzaque, Mohammed S

Current research in physiology

2022 Volume 5, Page(s) 203–207

Abstract	Zinc is an essential mineral with an important relationship with vitamin D. Studies have found that reduced blood zinc levels could predict vitamin D deficiency in adolescent girls, while zinc supplementation increased vitamin D levels in postmenopausal women. In vitro studies using human peritoneal macrophages have found that zinc induced the release of calcitriol (1,25-dihydroxycholecalciferol). Zinc also acts as a cofactor for vitamin D functions, as the transcriptional activity of vitamin D-dependent genes relies on zinc to exert pleiotropic functions, including mineral ion regulation. Vitamin D could also induce zinc transporters to regulate zinc homeostasis. Together, zinc and vitamin D in adequate concentrations help maintain a healthy musculoskeletal system and beyond; however, deficiency in either of these nutrients can result in various disorders affecting almost all body systems. This brief article will focus on the role of zinc in vitamin D functions.
Language	English
Publishing date	2022-04-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2665-9441
ISSN (online)	2665-9441
DOI	10.1016/j.crphys.2022.04.001
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Article ; Online: Dissecting the causal polymorphism of the Lr67res multipathogen resistance gene.

Milne, Ricky J / Dibley, Katherine E / Bose, Jayakumar / Riaz, Adnan / Zhang, Jianping / Schnippenkoetter, Wendelin / Ashton, Anthony R / Ryan, Peter R / Tyerman, Stephen D / Lagudah, Evans S

Journal of experimental botany

2024

Abstract: Partial resistance to multiple biotrophic fungal pathogens in wheat (Triticum aestivum L.) is conferred by a variant of the Lr67 gene, which encodes a hexose-proton symporter. Two mutations (G144R, V387L) differentiate the resistant and susceptible ... ...

Abstract	Partial resistance to multiple biotrophic fungal pathogens in wheat (Triticum aestivum L.) is conferred by a variant of the Lr67 gene, which encodes a hexose-proton symporter. Two mutations (G144R, V387L) differentiate the resistant and susceptible protein variants (Lr67res and Lr67sus). Lr67res lacks sugar transport capability and was associated with anion transporter-like properties when expressed in Xenopus laevis oocytes. Here, we extended this functional characterization to include yeast and in planta studies. The Lr67res allele, but not Lr67sus, induced sensitivity to ions in yeast (including NaCl, LiCl, KI), which is consistent with our previous observations that Lr67res expression in oocytes induces novel ion fluxes. We demonstrate that another naturally occurring single amino acid variant in wheat, containing only the Lr67G144R mutation, confers rust resistance. Transgenic barley plants expressing the orthologous HvSTP13 gene carrying the G144R and V387L mutations were also more resistant to Puccinia hordei infection. NaCl treatment of pot-grown adult wheat plants with the Lr67res allele induced leaf tip necrosis and partial leaf rust resistance. An Lr67res-like function can be introduced into orthologous plant hexose transporters via single amino acid mutation, highlighting the strong possibility of generating disease resistance in other crops, especially with gene editing.
Language	English
Publishing date	2024-04-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2976-2
ISSN	1460-2431 ; 0022-0957
ISSN (online)	1460-2431
ISSN	0022-0957
DOI	10.1093/jxb/erae164
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Article: Genomics of

Nowlan, Joseph P / Sies, Ashton N / Britney, Scott R / Cameron, Andrew D S / Siah, Ahmed / Lumsden, John S / Russell, Spencer

Pathogens (Basel, Switzerland)

2023 Volume 12, Issue 1

Abstract: ... ...

Abstract	Tenacibaculum
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens12010101
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Article ; Online: Salmonella enterica

Kumwenda, Benjamin / Canals, Rocío / Predeus, Alexander V / Zhu, Xiaojun / Kröger, Carsten / Pulford, Caisey / Wenner, Nicolas / Lora, Lizeth Lacharme / Li, Yan / Owen, Siân V / Everett, Dean / Hokamp, Karsten / Heyderman, Robert S / Ashton, Philip M / Gordon, Melita A / Msefula, Chisomo L / Hinton, Jay C D

microLife

2024 Volume 5, Page(s) uqae005

Abstract: Invasive non- ... ...

Abstract	Invasive non-typhoidal
Language	English
Publishing date	2024-03-28
Publishing country	England
Document type	Journal Article
ISSN	2633-6693
ISSN (online)	2633-6693
DOI	10.1093/femsml/uqae005
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