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Iatrogenic hypoglycaemia remains a major barrier to optimal glycaemic control required to prevent long-term complications in people with type 1 diabetes (pwT1D). Hypoglycaemia is the consequence of the interaction between absolute or relative insulin excess from treatment and compromised physiological defences against falling plasma glucose. With a longer duration of diabetes and repeated exposure to hypoglycaemia, pwT1D can develop impaired awareness of hypoglycaemia (IAH). IAH increases the risk of severe hypoglycaemia six-fold, causing significant morbidity, and, if left untreated, death. Over the last few decades, a stepwise change in diabetes management has been the introduction and widespread uptake of novel technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems. These technologies aim to improve glycaemic control whilst minimising hypoglycaemia. Alarms and safety functions, such as suspension of insulin delivery, can help to reduce the hypoglycaemia burden. This review examines the role of continuous glucose monitors and AID systems in managing IAH, exploring evidence for their impact on symptomatic awareness and identifying areas for future research. In conclusion, there is strong evidence that CGM and AID systems improve glycaemic control and reduce the hypoglycaemia burden. However, despite the use of these technologies, severe hypoglycaemic episodes are not entirely eliminated, and it remains unclear whether their implementation restores the physiological symptoms and counter-regulatory response to hypoglycaemia. Plain language summary Staying safe from low blood sugar—the role of technology Type 1 diabetes occurs when the immune system damages cells in the pancreas that make and release insulin, a hormone needed to control sugar (glucose) levels in the blood. For people with type 1 diabetes, insulin treatment is essential and must be given by injection under the skin. Injections do not control glucose levels automatically and it is hard to match insulin doses to food and activity, resulting in both high and low blood sugar levels (hypoglycaemia). Avoiding high blood sugar is important to prevent long-term complications such as eye disease, whereas low blood sugar is dangerous as the brain needs a continuous sugar supply to function. If this supply is interrupted, it can stop the brain working normally and may lead to confusion, unconsciousness and, very rarely, death. When blood sugar drops, the body releases chemical messengers that can raise glucose levels and cause symptoms warning people their glucose is falling. In long-standing type 1 diabetes, some people lose early symptoms of low blood sugar, leading to a condition called impaired awareness of hypoglycaemia. This makes them more likely to develop severely low glucose levels. New technologies like continuous glucose monitors (CGMs) and automatic insulin delivery systems (AID, sometimes known as the artificial pancreas) have revolutionised diabetes management. CGM can track glucose levels continuously and warn people when levels are falling, while AID systems automatically adjust insulin delivery, aiming to keep blood sugar within a safe range. This review examines the evidence behind CGM and AID systems in treating people with impaired awareness of hypoglycaemia. While these technologies improve blood sugar control and reduce hypoglycaemic events, they do not completely eliminate them. Importantly, it remains unclear whether these devices help people regain the ability to recognise early warning signs of low blood sugar.

Crop diseases reduce wheat yields by ~25% globally and thus pose a major threat to global food security 1 . Genetic resistance can reduce crop losses in the field and can be selected through the use of molecular markers. However, genetic resistance often breaks down following changes in pathogen virulence, as experienced with the wheat yellow (stripe) rust fungus Puccinia striiformis f. sp. tritici ( Pst ) 2 . This highlights the need to (1) identify genes that, alone or in combination, provide broad-spectrum resistance, and (2) increase our understanding of the underlying molecular modes of action. Here we report the isolation and characterization of three major yellow rust resistance genes ( Yr7 , Yr5 and YrSP ) from hexaploid wheat ( Triticum aestivum ), each having a distinct recognition specificity. We show that Yr5 , which remains effective to a broad range of Pst isolates worldwide, is closely related yet distinct from Yr7 , whereas YrSP is a truncated version of Yr5 with 99.8% sequence identity. All three Yr genes belong to a complex resistance gene cluster on chromosome 2B encoding nucleotide-binding and leucine-rich repeat proteins (NLRs) with a non-canonical N-terminal zinc-finger BED domain 3 that is distinct from those found in non-NLR wheat proteins. We developed diagnostic markers to accelerate haplotype analysis and for marker-assisted selection to expedite the stacking of the non-allelic Yr genes. Our results provide evidence that the BED-NLR gene architecture can provide effective field-based resistance to important fungal diseases such as wheat yellow rust. Crop fungal diseases pose great threats to global food security. This study isolates and characterizes three BED-domain-containing immune receptor genes from hexaploid wheat that confer resistance to yellow rust with distinct recognition specificities.

Field sport coaches must use reliable and valid tests to assess change-of-direction speed in their athletes. Few tests feature linear sprinting with acute change- of-direction maneuvers. The Change-of-Direction and Acceleration Test (CODAT) was designed to assess field sport change-of-direction speed, and includes a linear 5-meter (m) sprint, 45° and 90° cuts, 3- m sprints to the left and right, and a linear 10-m sprint. This study analyzed the reliability and validity of this test, through comparisons to 20-m sprint (0-5, 0-10, 0-20 m intervals) and Illinois agility run (IAR) performance. Eighteen Australian footballers (age = 23.83 ± 7.04 yrs; height = 1.79 ± 0.06 m; mass = 85.36 ± 13.21 kg) were recruited. Following familiarization, subjects completed the 20-m sprint, CODAT, and IAR in 2 sessions, 48 hours apart. Intra-class correlation coefficients (ICC) assessed relative reliability. Absolute reliability was analyzed through paired samples t-tests (p ≤ 0.05) determining between-session differences. Typical error (TE), coefficient of variation (CV), and differences between the TE and smallest worthwhile change (SWC), also assessed absolute reliability and test usefulness. For the validity analysis, Pearson's correlations (p ≤ 0.05) analyzed between-test relationships. Results showed no between-session differences for any test (p = 0.19-0.86). CODAT time averaged ~6 s, and the ICC and CV equaled 0.84 and 3.0%, respectively. The homogeneous sample of Australian footballers meant that the CODAT's TE (0.19 s) exceeded the usual 0.2 x standard deviation (SD) SWC (0.10 s). However, the CODAT is capable of detecting moderate performance changes (SWC calculated as 0.5 x SD = 0.25 s). There was a near perfect correlation between the CODAT and IAR (r = 0.92), and very large correlations with the 20-m sprint (r = 0.75-0.76), suggesting that the CODAT was a valid change-of-direction speed test. Due to movement specificity, the CODAT has value for field sport assessment. Key pointsThe change-of-direction and acceleration test (CODAT) was designed specifically for field sport athletes from specific speed research, and data derived from time-motion analyses of sports such as rugby union, soccer, and Australian football. The CODAT features a linear 5-meter (m) sprint, 45° and 90° cuts and 3-m sprints to the left and right, and a linear 10-m sprint.The CODAT was found to be a reliable change-of-direction speed assessment when considering intra-class correlations between two testing sessions, and the coefficient of variation between trials. A homogeneous sample of Australian footballers resulted in absolute reliability limitations when considering differences between the typical error and smallest worthwhile change. However, the CODAT will detect moderate (0.5 times the test's standard deviation) changes in performance.The CODAT correlated with the Illinois agility run, highlighting that it does assess change-of-direction speed. There were also significant relationships with short sprint performance (i.e. 0-5 m and 0-10 m), demonstrating that linear acceleration is assessed within the CODAT, without the extended duration and therefore metabolic limitations of the IAR. Indeed, the average duration of the test (~6 seconds) is field sport-specific. Therefore, the CODAT could be used as an assessment of change-of-direction speed in field sport athletes.

For new varieties to be sold, they must first pass assessment using a set of phenotypic criteria that test for distinctness, uniformity, and stability (DUS) and which serve as the basis for the awarding of plant breeders’ rights. The objective of this study was to use historical DUS phenotypic data to investigate the genetic architecture of DUS characteristics in wheat ( Triticum aestivum L.). Using a panel of 334 varieties, genome-wide association studies (GWAS) identified significant marker–trait associations for 18 of the 33 wheat DUS characteristics investigated. The most significant was the genetic locus P22_3B_821 for stem pith thickness, located between 818 and 830 Mb on chromosome 3B. Haplotype analysis informed conversion of three genetic markers selected from the genotyping array to the KASP genotyping platform, allowing alleles associated with low–medium versus thick pith thickness to be easily tracked. Subsequent genomic and molecular analysis found evidence that TaDof-B copy number variation (CNV) may underlie control of pith thickness in wheat, whereby CNV ≥3 was associated with the solid stem phenotype, analogous to that previously observed for TdDof-B in durum wheat ( T. turgidum subsp. durum ) and lower CNV with hollow stems. Finally, correlations between DUS characteristics with yield, grain quality traits, and year of release indicated that reduced ear density is under breeder selection and that this has a beneficial effect on the quality traits ‘grain test weight’ and ‘Hagberg falling number’. Collectively, these findings and molecular tools will help inform commercial, DUS regulatory and scientific advances in future wheat research and development programmes.

Wheat (Triticum aestivum L.) is a major source of nutrients for populations across the globe, but the amino acid composition of wheat grain does not provide optimal nutrition. The nutritional value of wheat grain is limited by low concentrations of lysine (the most limiting essential amino acid) and high concentrations of free asparagine (precursor to the processing contaminant acrylamide). There are currently few available solutions for asparagine reduction and lysine biofortification through breeding. In this study, we investigated the genetic architecture controlling grain free amino acid composition and its relationship to other traits in a Robigus × Claire doubled haploid population. Multivariate analysis of amino acids and other traits showed that the two groups are largely independent of one another, with the largest effect on amino acids being from the environment. Linkage analysis of the population allowed identification of quantitative trait loci (QTL) controlling free amino acids and other traits, and this was compared against genomic prediction methods. Following identification of a QTL controlling free lysine content, wheat pangenome resources facilitated analysis of candidate genes in this region of the genome. These findings can be used to select appropriate strategies for lysine biofortification and free asparagine reduction in wheat breeding programs. Core Ideas High free asparagine and low lysine concentrations limit the nutritional value of wheat grain. Investigation of a biparental mapping population formed from the UK soft wheats Claire and Robigus. Breeding for lower free asparagine and higher lysine using Claire and Robigus diversity is possible but limited.

Background Little is known about the initial, symptomless (latent) phase of the devastating wheat disease Septoria tritici blotch. However, speculations as to its impact on fungal success and disease severity in the field have suggested that a long latent phase is beneficial to the host and can reduce inoculum build up in the field over a growing season. The winter wheat cultivar Stigg is derived from a synthetic hexaploid wheat and contains introgressions from wild tetraploid wheat Triticum turgidum subsp. dicoccoides , which contribute to cv. Stigg’s exceptional STB resistance, hallmarked by a long latent phase. We compared the early transcriptomic response to Zymoseptoria tritici of cv. Stigg to a susceptible wheat cultivar, to elucidate the mechanisms of and differences in pathogen recognition and disease response in these two hosts. Results The STB-susceptible cultivar Longbow responds to Z. tritici infection with a stress response, including activation of hormone-responsive transcription factors, post translational modifications, and response to oxidative stress. The activation of key genes associated with these pathways in cv. Longbow was independently observed in a second susceptible wheat cultivar based on an independent gene expression study. By comparison, cv. Stigg is apathetic in response to STB, and appears to fail to activate a range of defence pathways that cv. Longbow employs. Stigg also displays some evidence of sub-genome bias in its response to Z. tritici infection, whereas the susceptible cv. Longbow shows even distribution of Z. tritici responsive genes across the three wheat sub-genomes. Conclusions We identify a suite of disease response genes that are involved in early pathogen response in susceptible wheat cultivars that may ultimately lead to susceptibility. In comparison, we hypothesise that rather than an active defence response to stave off disease progression, cv. Stigg’s defence strategy is molecular lethargy, or a lower-amplitude of pathogen recognition that may stem from cv. Stigg’s wild wheat-derived ancestry. Overall, we present insights into cv. Stigg’s exceptional resistance to STB, and present key biological processes for further characterisation in this pathosystem.

Genetic diversity in modern sunflower (Helianthus annuus L.) cultivars (elite oilseed inbred lines) has been shaped by domestication and breeding bottlenecks and wild and exotic allele introgression−the former narrowing and the latter broadening genetic diversity. To assess single nucleotide polymorphism (SNP) frequencies, nucleotide diversity, and linkage disequilibrium (LD) in modern cultivars, alleles were resequenced from 81 genic loci distributed throughout the sunflower genome. DNA polymorphisms were abundant; 1078 SNPs (1/45.7 bp) and 178 insertions-deletions (INDELs) (1/277.0 bp) were identified in 49.4 kbp of DNA/genotype. SNPs were twofold more frequent in noncoding (1/32.1 bp) than coding (1/62.8 bp) sequences. Nucleotide diversity was only slightly lower in inbred lines (θ = 0.0094) than wild populations (θ = 0.0128). Mean haplotype diversity was 0.74. When extraploted across the genome (∼3500 Mbp), sunflower was predicted to harbor at least 76.4 million common SNPs among modern cultivar alleles. LD decayed more slowly in inbred lines than wild populations (mean LD declined to 0.32 by 5.5 kbp in the former, the maximum physical distance surveyed), a difference attributed to domestication and breeding bottlenecks. SNP frequencies and LD decay are sufficient in modern sunflower cultivars for very high-density genetic mapping and high-resolution association mapping.

Orange wheat blossom midge (OWBM, Sitodiplosis mosellana Géhin) is an important insect pest of wheat (Triticum aestivum) in many growing regions. Sm1 is the only described OWBM resistance gene and is the foundation of managing OWBM through host genetics. Sm1 was previously mapped to wheat chromosome arm 2BS relative to simple sequence repeat (SSR) markers and the dominant, sequence characterized amplified region (SCAR) marker WM1. The objectives of this research were to saturate the Sm1 region with markers, develop improved markers for marker-assisted selection (MAS), and examine the synteny between wheat, Brachypodium distachyon, and rice (Oryza sativa) in the Sm1 region. The present study mapped Sm1 in four populations relative to single nucleotide polymorphisms (SNPs), SSRs, Diversity Array Technology (DArT) markers, single strand conformation polymorphisms (SSCPs), and the SCAR WM1. Numerous high quality SNP assays were designed that mapped near Sm1. BLAST delineated the syntenic intervals in B. distachyon and rice using gene-based SNPs as query sequences. The Sm1 region in wheat was inverted relative to B. distachyon and rice, which suggests a chromosomal rearrangement within the Triticeae lineage. Seven SNPs were tested on a collection of wheat lines known to carry Sm1 and not to carry Sm1. Sm1-flanking SNPs were identified that were useful for predicting the presence or absence of Sm1 based upon haplotype. These SNPs will be a major improvement for MAS of Sm1 in wheat breeding programs.

Simon Berry,1 Victoria Ship2 1Simon Berry Optometrist, Durham, UK; 2Dove Medical Press Ltd, Macclesfield, UK We are pleased to announce that Clinical Optometry has recently been accepted for indexing with PubMed. This is an exciting and important leap forward for this journal that began with humble beginnings as a sister journal to Clinical Ophthalmology when some of the articles submitted were more suited to an optometric audience. All articles published in Clinical Optometry are now available through PubMed and PubMed Central (Clin Optom (Auckl)), the Emerging Sources Citation Index (Web of Science), Scopus, Directory of Open Access Journals, OAIster, as well as through Dove Medical Press and Internet search engines such as Google. It is heartening that the scientific quality of these articles, and the peer review process, has been proven to be of a high enough standard for archiving.

Background Triticum monococcum (2 n = 2 x = 14) is an ancient diploid wheat with many useful traits and is used as a model for wheat gene discovery. DArT ( D iversity Ar rays T echnology) employs a hybridisation-based approach to type thousands of genomic loci in parallel. DArT markers were developed for T. monococcum to assess genetic diversity, compare relationships with hexaploid genomes, and construct a genetic linkage map integrating DArT and microsatellite markers. Results A DArT array, consisting of 2304 hexaploid wheat, 1536 tetraploid wheat, 1536 T. monococcum as well as 1536 T. boeoticum representative genomic clones, was used to fingerprint 16 T. monococcum accessions of diverse geographical origins. In total, 846 polymorphic DArT markers were identified, of which 317 were of T. monococcum origin, 246 of hexaploid, 157 of tetraploid, and 126 of T. boeoticum genomes. The fingerprinting data indicated that the geographic origin of T. monococcum accessions was partially correlated with their genetic variation. DArT markers could also well distinguish the genetic differences amongst a panel of 23 hexaploid wheat and nine T. monococcum genomes. For the first time, 274 DArT markers were integrated with 82 simple sequence repeat (SSR) and two morphological trait loci in a genetic map spanning 1062.72 cM in T. monococcum . Six chromosomes were represented by single linkage groups, and chromosome 4A m was formed by three linkage groups. The DArT and SSR genetic loci tended to form independent clusters along the chromosomes. Segregation distortion was observed for one third of the DArT loci. The Ba (black awn) locus was refined to a 23.2 cM region between the DArT marker locus wPt-2584 and the microsatellite locus Xgwmd33 on 1A m ; and the Hl (hairy leaf) locus to a 4.0 cM region between DArT loci 376589 and 469591 on 5A m . Conclusion DArT is a rapid and efficient approach to develop many new molecular markers for genetic studies in T. monococcum . The constructed genetic linkage map will facilitate localisation and map-based cloning of genes of interest, comparative mapping as well as genome organisation and evolution studies between this ancient diploid species and other crops.