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To safeguard bread wheat against pests and diseases, breeders have introduced over 200 resistance genes into its genome, thus nearly doubling the number of designated resistance genes in the wheat gene pool1. Isolating these genes facilitates their fast-tracking in breeding programs and incorporation into polygene stacks for more durable resistance. We cloned the stem rust resistance gene Sr43, which was crossed into bread wheat from the wild grass Thinopyrum elongatum2,3. Sr43 encodes an active protein kinase fused to two domains of unknown function. The gene, which is unique to the Triticeae, appears to have arisen through a gene fusion event 6.7 to 11.6 million years ago. Transgenic expression of Sr43 in wheat conferred high levels of resistance to a wide range of isolates of the pathogen causing stem rust, highlighting the potential value of Sr43 in resistance breeding and engineering.

Wheat stem rust, caused by Puccinia graminis f. sp. tritici, is a re-emerging disease, posing a threat to wheat production. In Spain, stem rust has been rarely detected since the 1970s, but infection was observed in wheat fields in 2018. We analysed six stem rust samples collected in Rota, Cádiz province and one from Monteagudo del Castillo, Teruel province. All the samples from Rota were typed as race TKTTF, whereas the sample from Monteagudo del Castillo, collected in a wheat field adjacent to barberry bushes, was typed as race TKHBK. This race has a unique and significant virulence combination that includes virulence to Sr31, Sr33, Sr53 and Sr59, and is avirulent to Rusty, a durum line developed for universal susceptibility to the wheat stem rust pathogen. TKHBK is the first race outside the Ug99 race group with virulence to Sr31 and the first known race with virulence to Sr59. Genotyping studies indicate that race TKHBK does not belong to the Ug99 or TKTTF race groups and constitutes a previously unknown lineage. Two hundred bread and durum wheat cultivars and breeding lines from Spain were evaluated against TKHBK, TKTTF, and six additional races. Resistance was observed to all the races evaluated. Molecular markers confirmed the presence of Sr7a, Sr24, Sr31, Sr38 and Sr57 in bread wheat, and Sr13 in durum wheat. The re-emergence of wheat stem rust in Spain and the occurrence of unique virulences underscore the need to continue surveying and monitoring this disease. info:eu-repo/semantics/acceptedVersion

Key message The diploid wheat recessive stem rust resistance gene SrTm4 was fine-mapped to a 754-kb region on chromosome arm 2AmL and potential candidate genes were identified. Abstract Race Ug99 of Puccinia graminis f. sp. tritici (Pgt), the causal agent of wheat stem (or black) rust is one of the most serious threats to global wheat production. The identification, mapping, and deployment of effective stem rust resistance (Sr) genes are critical to reduce this threat. In this study, we generated SrTm4 monogenic lines and found that this gene confers resistance to North American and Chinese Pgt races. Using a large mapping population (9522 gametes), we mapped SrTm4 within a 0.06 cM interval flanked by marker loci CS4211 and 130K1519, which corresponds to a 1.0-Mb region in the Chinese Spring reference genome v2.1. A physical map of the SrTm4 region was constructed with 11 overlapping BACs from the resistant Triticum monococcum PI 306540. Comparison of the 754-kb physical map with the genomic sequence of Chinese Spring and a discontinuous BAC sequence of DV92 revealed a 593-kb chromosomal inversion in PI 306540. Within the candidate region, we identified an L-type lectin-domain containing receptor kinase (LLK1), which was disrupted by the proximal inversion breakpoint, as a potential candidate gene. Two diagnostic dominant markers were developed to detect the inversion breakpoints. In a survey of T. monococcum accessions, we identified 10 domesticated T. monococcum subsp. monococcum genotypes, mainly from the Balkans, carrying the inversion and showing similar mesothetic resistant infection types against Pgt races. The high-density map and tightly linked molecular markers developed in this study are useful tools to accelerate the deployment of SrTm4-mediated resistance in wheat breeding programs.

Impaired social cognition is a core deficit of frontotemporal dementia (FTD). It is most commonly associated with the behavioural-variant of FTD, with atrophy of the orbitofrontal and ventromedial prefrontal cortex. However, social cognitive changes are also common in semantic dementia, with atrophy centred on the anterior temporal lobes. The impairment of social behaviour in FTD has typically been attributed to damage to the orbitofrontal cortex and/or temporal poles and/or the uncinate fasciculus that connects them. However, the relative contribution of each region is unresolved. In this review, we present a unified neurocognitive model of controlled social behaviour that not only explains the observed impairment of social behaviours in FTD, but also assimilates findings from other patient groups, comparative neurology, and normative cognitive neuroscience. We propose that impaired social behaviour results from damage to two cognitively- and anatomically-distinct components. The first component is social-semantic knowledge, supported by the anterior temporal lobes bilaterally. The second component is social control, supported by the orbitofrontal cortex, medial frontal cortex and ventrolateral frontal cortex, which interact with social-semantic knowledge to guide and shape social behaviour.

Wheat stem rust caused by Puccinia graminis f. sp. tritici is a widespread and recurring threat to wheat production. Emerging P. graminis f. sp. tritici variants are rapidly overcoming major gene resistance deployed in wheat cultivars and new sources of race-nonspecific resistance are urgently needed. The National Small Grains Collection (NSGC) contains thousands of wheat landrace accessions that may harbor unique and broadly effective sources of resistance to emerging P. graminis f. sp. tritici variants. All NSGC available facultative and winter-habit bread wheat landraces were tested in a field nursery in St. Paul, Minnesota, against a bulk collection of six common U.S. P. graminis f. sp. tritici races. Infection response and severity data were collected on 9,192 landrace accessions at the soft-dough stage and resistant accessions were derived from single spikes. Derived accessions were tested in St. Paul a second time to confirm resistance and in a field nursery in Njoro, Kenya against emerging races of P. graminis f. sp. tritici with virulence to many known resistance genes including Sr24, Sr31, Sr38, and SrTmp. Accessions resistant in the St. Paul field were also tested at the seedling stage with up to 13 P. graminis f. sp. tritici races, including TTKSK and TKTTF, and with 19 molecular markers linked with known stem rust resistance genes or genes associated with modern breeding practices. Forty-five accessions were resistant in both U.S. and Kenya field nurseries and lacked alleles linked with known stem rust resistance genes. Accessions with either moderate or strong resistance in the U.S. and Kenya field nurseries and with novel seedling resistance will be prioritized for further study.

Wheat stem (or black) rust, caused by Puccinia graminis f. sp. tritici (Pgt), has been historically among the most devastating global fungal diseases of wheat. The recent occurrence and spread of new virulent races such as Ug99 have prompted global efforts to identify and isolate more effective stem rust resistance (Sr) genes. Here, we report the map-based cloning of the Ug99-effective SrTm5 gene from diploid wheat Triticum monococcum accession PI 306540 that encodes a typical coiled-coil nucleotide-binding leucine-rich repeat protein. This gene, designated as Sr22b, is a new allele of Sr22 with a rare insertion of a large (13.8-kb) retrotransposon into its second intron. Biolistic transformation of an ~112-kb circular bacterial artificial chromosome plasmid carrying Sr22b into the susceptible wheat variety Fielder was sufficient to confer resistance to stem rust. In a survey of 168 wheat genotypes, Sr22b was present only in cultivated T. monococcum subsp. monococcum accessions but absent in all tested tetraploid and hexaploid wheat lines. We developed a diagnostic molecular marker for Sr22b and successfully introgressed a T. monococcum chromosome segment containing this gene into hexaploid wheat to accelerate its deployment and pyramiding with other Sr genes in wheat breeding programmes. Sr22b can be a valuable component of gene pyramids or transgenic cassettes combining different resistance genes to control this devastating disease.

Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. We advocate that biophysical models of neurophysiology offer both a bridge from clinical to preclinical models of pathology, and quantitative assays for experimental medicine. Such biophysical models can also disclose hidden neuronal dynamics generating neurophysiological observations like electro- and magneto-encephalography (MEG). Here, we augment a biophysically informed mesoscale model of human cortical function by inclusion of synaptic density estimates as captured by [11C]UCB-J positron emission tomography, and provide insights into how regional synapse loss affects neurophysiology. We use the primary tauopathy of progressive supranuclear palsy (Richardson’s syndrome) as an exemplar condition, with high clinicopathological correlations. Progressive supranuclear palsy causes a marked change in cortical neurophysiology in the presence of mild atrophy and is associated with a decline in cognitive functions associated with the frontal lobe. Using (parametric empirical) Bayesian inversion of a conductance-based canonical microcircuit model of MEG data, we show that the inclusion of regional synaptic density—as a subject-specific prior on laminar specific neuronal populations—markedly increases model evidence. Specifically, model comparison suggests that a reduction in synaptic density in inferior frontal cortex affects superficial and granular layer glutamatergic excitation. This predicted individual differences in behaviour, demonstrating the link between synaptic loss, neurophysiology, and cognitive deficits. The method we demonstrate is not restricted to progressive supranuclear palsy or the effects of synaptic loss: such pathology-enriched dynamic causal models can be used to assess the mechanisms of other neurological disorders, with diverse non-invasive measures of pathology, and is suitable to test the effects of experimental pharmacology.

Barley leaf rust (BLR), caused by Puccinia hordei, is best controlled through genetic resistance. An efficient resistance breeding program prioritizes the need to identify, characterize, and map new sources of resistance as well as understanding the effectiveness, structure, and function of resistance genes. In this study, three mapping populations were developed by crossing Israelian barley lines “AGG-396,” “AGG-397,” and “AGG-403” (carrying unknown leaf rust resistance) with a susceptible variety “Gus” to characterize and map resistance. Genetic analysis of phenotypic data from rust testing F3s with a P. hordei pathotype 5457 P+ revealed monogenic inheritance in all three populations. Targeted genotyping-by-sequencing of the three populations detected marker trait associations in the same genomic region on the short arm of chromosome 2H between 39 and 57 Mb (AGG-396/Gus), 44 and 64 Mb (AGG-397/Gus), and 31 and 58 Mb (AGG-403/Gus), suggesting that the resistance in all three lines is likely conferred by the same locus (tentatively designated RphAGG396). Two Kompetitive allele-specific PCR (KASP) markers, HvGBSv2-902 and HvGBSv2-932, defined a genetic distance of 3.8 cM proximal and 7.1 cM distal to RphAGG396, respectively. To increase the marker density at the RphAGG396 locus, 75 CAPS markers were designed between two flanking markers. Integration of marker data resulted in the identification of two critical recombinants and mapping RphAGG396 between markers- Mloc-28 (40.75 Mb) and Mloc-41 (41.92 Mb) narrowing the physical window to 1.17 Mb based on the Morex v2.0 reference genome assembly. To enhance map resolution, 600 F2s were genotyped with markers- Mloc-28 and Mloc-41 and nine recombinants were identified, placing the gene at a genetic distance of 0.5 and 0.2 cM between the two markers, respectively. Two annotated NLR (nucleotide-binding domain leucine-rich repeat) genes (r2.2HG0093020 and r2.2HG0093030) were identified as the best candidates for RphAGG396. A closely linked marker was developed for RphAGG396 that can be used for marker-assisted selection.

SUMMARY The resistance gene Sr13 is one of the most important genes in durum wheat for controlling stem rust caused by Puccinia graminis f. sp. tritici (Pgt). The Sr13 functional gene CNL13 has haplotypes R1, R2 and R3. The R1/R3 and R2 haplotypes were originally designated as alleles Sr13a and Sr13b, respectively. To detect additional Sr13 alleles, we developed Kompetitive allele specific PCR (KASP™) marker KASPSr13 and four semi‐thermal asymmetric reverse PCR markers, rwgsnp37–rwgsnp40, based on the CNL13 sequence. These markers were shown to detect R1, R2 and R3 haplotypes in a panel of diverse tetraploid wheat accessions. We also observed the presence of Sr13 in durum line CAT‐A1, although it lacked any of the known haplotypes. Sequence analysis revealed that CNL13 of CAT‐A1 differed from the susceptible haplotype S1 by a single nucleotide (C2200T) in the leucine‐rich repeat region and differed from the other three R haplotypes by one or two additional nucleotides, confirming that CAT‐A1 carries a new (R4) haplotype. Stem rust tests on the monogenic, transgenic and mutant lines showed that R1 differed from R3 in its susceptibility to races TCMJC and THTSC, whereas R4 differed from all other haplotypes for susceptibility to TTKSK, TPPKC and TCCJC. Based on these differences, we designate the R1, R3 and R4 haplotypes as alleles Sr13a, Sr13c and Sr13d, respectively. This study indicates that Sr13d may be the primitive functional allele originating from the S1 haplotype via a point mutation, with the other three R alleles probably being derived from Sr13d through one or two additional point mutations., Significance Statement A new resistant haplotype (R4) of Sr13, designated as Sr13d, was identified in the genotype CAT‐A1, and based on sequencing studies this allele is hypothesized to be a primitive functional resistant allele of Sr13. We established from extensive rust tests that haplotypes R1 and R3 should be separated, and R3 was designated Sr13c and determined to be preferable to Sr13a for breeding, while Sr13d was undesirable for breeding due to susceptibility to stem rust Ug99.

AC Taber is a hard red spring wheat cultivar that has had long-lasting resistance to the leaf rust fungus Puccinia triticina. The objective of this study was to determine the chromosome location of the leaf rust resistance genes in AC Taber. The leaf rust-susceptible cultivar Thatcher was crossed with AC Taber to develop an F6 recombinant inbred line (RIL) population. The RILs and parents were evaluated for segregation of leaf rust resistance in five field plot tests and in two seedling tests to race BBBDB of P. triticina. A genetic map of the RIL population was developed using 90,000 single nucleotide polymorphism markers with the Illumina Infinium iSelect 90K wheat bead array. Quantitative trait loci (QTLs) with significant effects for lower leaf rust severity in the field plot tests were found on chromosomes 2BS and 3BS. The same QTLs also had significant effects for lower infection type in seedlings to leaf rust race BBBDB. The gene on 2BS was the adult plant resistance gene Lr13, and the gene on 3BS mapped to the same region as the adult plant resistance gene Lr74 and other QTLs for leaf rust resistance. Kompetitive allele-specific PCR assay markers linked to the 2BS and 3BS regions were developed and should be useful for marker-based selection of these genes.

Stem rust of wheat (Triticum spp.), caused by Puccinia graminis f. sp. tritici (Pgt), is one of the most impactful wheat diseases because of its threat to global wheat production. While disease mitigation has primarily been achieved through the deployment of resistant wheat varieties, emerging new virulent races continue to pose risks to the crop. For example, races such as Ug99 (TTKSK), TKTTF, and TTRTF have caused epidemics in different wheat growing regions of the world in recent years. A continual search for new and effective sources of resistance is therefore necessary to safeguard wheat production. This study assessed a breeding panel from the Ethiopian Institute of Agricultural Research (EIAR) wheat breeding program for seedling and field plant resistance to TTRTF and reports genomic regions conferring resistance to TTRTF. Trait correlations (r) were medium to strong (range = .38-.71) and heritabilities were moderate (.32-.56). Association analysis for resistance to TTRTF resulted in detection of 20 markers in 11 chromosomes; the marker S1B_175439851 was associated with resistance at both seedling and adult plant stages. Models with two to four QTL combinations reduced seedling and field disease severity by 12-48 and 9-17%, respectively. Genomic prediction for TTRTF resistance resulted in low to moderately-high predictions (mean correlations of .25-.47). Identification of resistant lines and QTL in the EIAR population is expected to assist in selection toward improved resistance to TTRTF. Specifically, the application of genomic selection (GS) in identifying resistant lines in future related breeding populations will further assist breeding efforts against this new stem rust pathogen race.

The winter wheat (Triticum aestivum L.) line CI13227 has been characterized as having adult plant resistance to leaf rust caused by Puccinia triticina Eriks (Pt). Line CI13227 was crossed with the susceptible spring wheat 'Thatcher' (Tc) and a Tc*2/CI13227 F

In the last 20 years, severe wheat stem rust outbreaks have been recorded in Africa, Europe, and Central Asia. This previously well controlled disease, caused by the fungus Puccinia graminis f. sp. tritici, has reemerged as a major threat to wheat cultivation. The stem rust (Sr) resistance gene Sr22 encodes a nucleotide-binding and leucine-rich repeat receptor which confers resistance to the highly virulent African stem rust isolate Ug99. Here, we show that the Sr22 gene is conserved among grasses in the Triticeae and Poeae lineages. Triticeae species contain syntenic loci with single-copy orthologs of Sr22 on chromosome 7, except Hordeum vulgare, which has experienced major expansions and rearrangements at the locus. We also describe 14 Sr22 sequence variants obtained from both Triticum boeoticum and the domesticated form of this species, T. monococcum, which have been postulated to encode both functional and nonfunctional Sr22 alleles. The nucleotide sequence analysis of these alleles identified historical sequence exchange resulting from recombination or gene conversion, including breakpoints within codons, which expanded the coding potential at these positions by introduction of nonsynonymous substitutions. Three Sr22 alleles were transformed into wheat cultivar Fielder and two postulated resistant alleles from Schomburgk (hexaploid wheat introgressed with T. boeoticum segment carrying Sr22) and T. monococcum accession PI190945, respectively, conferred resistance to P. graminis f. sp. tritici race TTKSK, thereby unequivocally confirming Sr22 effectiveness against Ug99. The third allele from accession PI573523, previously believed to confer susceptibility, was confirmed as nonfunctional against Australian P. graminis f. sp. tritici race 98-1,2,3,5,6. [Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Objectives To compare the clinical performance of a universal adhesive in class V non-carious cervical lesions (NCCLs) using two surface treatment protocols (self-etch [SfE] vs selective-enamel-etch [SelE]). Material and methods Thirty-three adults, each with ≥2 NCCLs, received one resin composite restoration utilizing a SfE universal adhesive and another utilizing the adhesive and SelE with 37% phosphoric acid. Restorations were evaluated for sensitivity, retention, marginal discoloration, marginal adaptation, and clinical acceptability through 24 months using Cochran-Mantel-Haenszel tests for stratified, ordered categorical outcomes. Results Sixty-six restorations (35 SfE, 31 SelE; 27 volunteers) were evaluated at 24 months. There were no significant differences between SfE and SelE for sensitivity, retention, marginal adaptation, or clinical acceptability. One SfE restoration was lost. Marginal adaptation was significantly worse at 24 months than baseline for SelE (P = 0.01), but not for SfE. Marginal discoloration was significantly worse for SfE (P = 0.02), but not for SelE. Sensitivity improved from baseline to 24 months for both groups (SelE P = 0.004, SfE P = 0.002). Conclusions Twenty-four-month data indicated significantly reduced sensitivity for both groups, worse marginal discoloration for SfE, and worse marginal adaptation for SelE. No changes in retention or clinical acceptability were observed in either group. All retained restorations were clinically acceptable at 24 months. Clinical significance Both self-etch and selective enamel etch techniques with a universal adhesive produced clinically acceptable results in resin composite restorations for NCCLs over 2 years.

Wheat (Triticum aestivum L.) rusts are a worldwide production problem. Plant breeders have used genetic resistance to combat these fungi. However, single-gene resistance is rapidly overcome as a result of frequent occurrence of new virulent fungal strains. Thus, a supply of new resistance sources is continually needed, and new resistance sources are limited within hexaploid wheat genetic stocks. Wild relatives are able to be a resource for new resistance genes but are hindered because of chromosome incapability with domesticated wheats. Twenty-eight double-haploid hexaploid wheat/Amblyopyrum muticum (Boiss.) Eig introgression lines, with introgressions covering the majority of the T genome, were evaluated for resistance to Puccinia triticina Erikss., P. graminis Pers.:Pers. f.sp. tritici Erikss. & E. Henning, and P. striiformis Westend. f.sp. tritici Erikss.. At the seedling level, four lines were resistant to races of P. triticina, six lines were resistant to P. graminis, and 15 lines were resistant to P. striiformis. At the adult stage, 16 lines were resistant to P. triticina. Line 355 had resistance to all three rusts and line 161 had resistance to all tested races of P. triticina. Some of these lines will require further work to reduce the size of the introgressed segment; however, lines 92 and 355 have very small fragments and can be used directly as new resistance donors.

See Piguet (doi:10.1093/brain/awaa119) for a scientific commentary on this article. Murley et al. report the results of a transdiagnostic study of clinical phenotype and brain atrophy in frontotemporal lobar degeneration syndromes, showing that these syndromes exist on a multidimensional spectrum, rather than as discrete entities., The syndromes caused by frontotemporal lobar degeneration have highly heterogeneous and overlapping clinical features. There has been great progress in the refinement of clinical diagnostic criteria in the past decade, but we propose that a better understanding of aetiology, pathophysiology and symptomatic treatments can arise from a transdiagnostic approach to clinical phenotype and brain morphometry. In a cross-sectional epidemiological study, we examined 310 patients with a syndrome likely to be caused by frontotemporal lobar degeneration, including behavioural variant frontotemporal dementia, non-fluent, and semantic variants of primary progressive aphasia (PPA), progressive supranuclear palsy and corticobasal syndrome. We included patients with logopenic PPA and those who met criteria for PPA but not a specific subtype. To date, 49 patients have a neuropathological diagnosis. A principal component analysis identified symptom dimensions that broadly recapitulated the core features of the main clinical syndromes. However, the subject-specific scores on these dimensions showed considerable overlap across the diagnostic groups. Sixty-two per cent of participants had phenotypic features that met the diagnostic criteria for more than one syndrome. Behavioural disturbance was prevalent in all groups. Forty-four per cent of patients with corticobasal syndrome had progressive supranuclear palsy-like features and 30% of patients with progressive supranuclear palsy had corticobasal syndrome-like features. Many patients with progressive supranuclear palsy and corticobasal syndrome had language impairments consistent with non-fluent variant PPA while patients with behavioural variant frontotemporal dementia often had semantic impairments. Using multivariate source-based morphometry on a subset of patients (n = 133), we identified patterns of covarying brain atrophy that were represented across the diagnostic groups. Canonical correlation analysis of clinical and imaging components found three key brain-behaviour relationships, with a continuous spectrum across the cohort rather than discrete diagnostic entities. In the 46 patients with follow-up (mean 3.6 years) syndromic overlap increased with time. Together, these results show that syndromes associated with frontotemporal lobar degeneration do not form discrete mutually exclusive categories from their clinical features or structural brain changes, but instead exist in a multidimensional spectrum. Patients often manifest diagnostic features of multiple disorders while deficits in behaviour, movement and language domains are not confined to specific diagnostic groups. It is important to recognize individual differences in clinical phenotype, both for clinical management and to understand pathogenic mechanisms. We suggest that a transdiagnostic approach to the spectrum of frontotemporal lobar degeneration syndromes provides a useful framework with which to understand disease aetiology, progression, and heterogeneity and to target future treatments to a higher proportion of patients.

Key message: Stem rust resistance genes, SrRL5271 and Sr672.1 as well as SrCPI110651, from Aegilops tauschii, the diploid D genome progenitor of wheat, are sequence variants of Sr46 differing by 1–2 nucleotides leading to non-synonymous amino acid substitutions. Abstract: The Aegilops tauschii (wheat D-genome progenitor) accessions RL 5271 and CPI110672 were identified as resistant to multiple races (including the Ug99) of the wheat stem rust pathogen Puccinia graminis f. sp. tritici (Pgt). This study was conducted to identify the stem rust resistance (Sr) gene(s) in both accessions. Genetic analysis of the resistance in RL 5271 identified a single dominant allele (SrRL5271) controlling resistance, whereas resistance segregated at two loci (SR672.1 and SR672.2) for a cross of CPI110672. Bulked segregant analysis placed SrRL5271 and Sr672.1 in a region on chromosome arm 2DS that encodes Sr46. Molecular marker screening, mapping and genomic sequence analysis demonstrated SrRL5271 and Sr672.1 are alleles of Sr46. The amino acid sequence of SrRL5271 and Sr672.1 is identical but differs from Sr46 (hereafter referred to as Sr46_h1 by following the gene nomenclature in wheat) by a single amino acid (N763K) and is thus designated Sr46_h2. Screening of a panel of Ae. tauschii accessions identified an additional allelic variant that differed from Sr46_h2 by a different amino acid (A648V) and was designated Sr46_h3. By contrast, the protein encoded by the susceptible allele of Ae. tauschii accession AL8/78 differed from these resistance proteins by 54 amino acid substitutions (94% nucleotide sequence gene identity). Cloning and complementation tests of the three resistance haplotypes confirmed their resistance to Pgt race 98-1,2,3,5,6 and partial resistance to Pgt race TTRTF in bread wheat. The three Sr46 haplotypes, with no virulent races detected yet, represent a valuable source for improving stem resistance in wheat.

Synaptic loss is an early feature of neurodegenerative disease models, and is often severe inpost mortemclinical studies, including frontotemporal dementia. Positron emission tomography (PET) imaging with radiotracers that bind to synaptic vesicle glycoprotein 2A enables quantification of synapsesin vivo. This study used [11C]UCB-J PET in people with behavioural variant frontotemporal dementia (bvFTD), testing the hypothesis that synaptic loss is severe and related to clinical severity. We performed a cross-sectional observational study of bvFTD,versushealthy controls, in which participants underwent neurological examination, neuropsychological assessment, magnetic resonance imaging (MRI) and [11C]UCB-J PET. Patients were recruited from the Cambridge Centre for Frontotemporal Dementia at the University of Cambridge, and healthy volunteers from the UK National Institute for Health Research Join Dementia Research register. Eleven people with a clinical diagnosis of probable bvFTD and 25 age- and sex-matched healthy controls were included. All participants underwent dynamic [11C]UCB-J PET imaging, structural MRI and a neuropsychological battery, including the Addenbrooke’s cognitive examination (ACE-R), and INECO frontal screening (IFS). General linear models were used to compare [11C]UCB-J binding potential maps between groups, and correlate synaptic density with cognitive performance and clinical features in patients. Group-comparison and correlation analyses were also performed using partial-volume corrected [11C]UCB-J binding potential from regions of interest (ROIs). Patients with bvFTD showed severe synaptic loss compared to controls. In particular, [11C]UCB-J binding was significantly reduced bilaterally in medial and dorsolateral frontal regions, inferior frontal gyri, anterior and posterior cingulate gyrus, insular cortex and medial temporal lobe. Synaptic loss in the left frontal and cingulate regions correlated significantly with cognitive impairments as assessed with ACE-R and IFS. Results from ROI-based analyses mirrored the voxel-wise results. In keeping with preclinical models, and human post mortem data, there is widespread frontotemporal loss of synapses in symptomatic bvFTD, in proportion to disease severity. [11C]UCB-J PET could support translational studies and experimental medicines strategies for new disease-modifying treatments for neurodegeneration.

Adult plant resistance (APR) to wheat stem rust has been one of the approaches for resistance breeding since the evolution of the Ug99 race group and other races. This study was conducted to dissect and understand the genetic basis of APR to stem rust in spring wheat line ‘Copio’. A total of 176 recombinant inbred lines (RILs) from the cross of susceptible parent ‘Apav’ with Copio were phenotyped for stem rust resistance in six environments. Composite interval mapping using 762 genotyping-by-sequencing markers identified 16 genomic regions conferring stem rust resistance. Assays with gene-linked molecular markers revealed that Copio carried known APR genes Sr2 and Lr46/Yr29/Sr58 in addition to the 2NS/2AS translocation that harbors race-specific genes Sr38, Lr37, and Yr17. Three quantitative trait loci (QTLs) were mapped on chromosomes 2B, two QTLs on chromosomes 3A, 3B, and 6A each, and one QTL on each of chromosomes 2A, 1B, 2D, 4B, 5D, 6D, and 7A. The QTL QSr.umn.5D is potentially a new resistance gene and contributed to quantitative resistance in Copio. The RILs with allelic combinations of Sr2, Sr38, and Sr58 had 27 to 39% less stem rust coefficient of infection in all field environments compared with RILs with none of these genes, and this gene combination was most effective in the U.S. environments. We conclude that Copio carries several genes that provide both race-specific and non–race-specific resistance to diverse races of stem rust fungus and can be used by breeding programs in pyramiding other effective genes to develop durable resistance in wheat.

Wheat stem rust, caused by Puccinia graminis f. sp. tritici, is a re-emerging disease exemplified by recent epidemics caused by new virulent races. Understanding the sources and origins of genetic variations in the pathogen populations globally can facilitate the development of better strategies in disease management. We analyzed 68 wheat stem rust samples collected between 2013 and 2015 from Georgia where stem rust incidences are frequent and the alternate host, common barberry, is present. A total of 116 single-pustule isolates were derived and evaluated on stem rust differential lines to determine the virulence phenotypes and 23 races were identified, many of which were detected for the first time. Unique virulence combinations including, Sr22+Sr24 and Sr13b+Sr35+Sr37 were detected. These virulence combinations pose new challenges to breeding programs because many of these genes are used in breeding for resistance to the Ug99 race group. Sixty-one isolates were genotyped using a custom single-nucleotide polymorphism chip and 17 genotypes were identified. The 2013 isolates contained 11 multilocus genotypes compared with isolates of 2014 and 2015, with five and three genotypes, respectively. The higher levels of virulence and genotypic diversity observed in the 2013 samples strongly indicated that sexual recombination occurs in the Georgian P. graminis f. sp. tritici population, and that the Caucasus region of Eurasia may be an important source of new races. [Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Wheat stem rust, caused by Puccinia graminis Pers. f. sp. tritici (Pgt), is a devastating fungal disease threatening global wheat production. The present paper reports the identification of stem rust resistance gene Sr60, a race-specific gene from diploid wheat Triticum monococcum L. that encodes a protein with two putative kinase domains. This gene, designated as WHEAT TANDEM KINASE 2 (WTK2), confers intermediate levels of resistance to Pgt. WTK2 was identified by map-based cloning and validated by transformation of a c.10-kb genomic sequence including WTK2 into susceptible common wheat variety Fielder (Triticum aestivum L.). Transformation of Fielder with WTK2 was sufficient to confer Pgt resistance. Sr60 transcripts were transiently upregulated 1 d post-inoculation with Pgt, but not in mock-inoculated plants. The upregulation of Sr60 was associated with stable upregulation of several pathogenesis-related genes. The Sr60-resistant haplotype found in T. monococcum was not found in polyploid wheat, suggesting an opportunity to introduce a novel resistance gene. Sr60 was successfully introgressed into hexaploid wheat, and we developed a diagnostic molecular marker to accelerate its deployment and pyramiding with other resistance genes. The cloned Sr60 also can be a useful component of transgenic cassettes including other resistance genes with complementary resistance profiles.

Bread wheat improvement using genomic tools is essential for accelerating trait genetic gains. Here we report the genomic predictabilities of 35 key traits and demonstrate the potential of genomic selection for wheat end-use quality. We also performed a large genome-wide association study that identified several significant marker–trait associations for 50 traits evaluated in South Asia, Africa and the Americas. Furthermore, we built a reference wheat genotype–phenotype map, explored allele frequency dynamics over time and fingerprinted 44,624 wheat lines for trait-associated markers, generating over 7.6 million data points, which together will provide a valuable resource to the wheat community for enhancing productivity and stress resilience. Large-scale genomic analyses in wheat identify regions associated with 50 agronomic traits evaluated in South Asia, Africa and the Americas. This genotype–phenotype map can be used to enhance wheat productivity and stress resilience.

Two stem rust resistance genes identified on chromosome arms 2BL and 6AL of the cultivated emmer wheat accession PI 193883 can be used for protecting modern varieties against Ug99 strains. The wheat research community consistently strives to identify new genes that confer resistance to stem rust caused by the fungal pathogen Puccinia graminis f. sp. tritici Eriks & E. Henn (Pgt). In the current study, our objective was to identify and genetically characterize the stem rust resistance derived from the cultivated emmer accession PI 193883. A recombinant inbred line population developed from a cross between the susceptible durum wheat line Rusty and PI 193883 was genotyped and evaluated for reaction to Pgt races TTKSK, TRTTF, and TMLKC. Two QTLs conferring resistance were identified on chromosome arms 2BL (QSr.fcu-2B) and 6AL (QSr.fcu-6A). The stem rust resistance gene (Sr883-2B) underlying QSr.fcu-2B was recessive, and based on its physical location it is located proximal to the Sr9 region. QSr.fcu-6A was located in the Sr13 region, but PI 193883 is known to carry the susceptible haplotype S4 for Sr13, indicating that the gene underlying QSr.fcu-6A (Sr883-6A) is likely a new allele of Sr13 or a gene residing close to Sr13. Three IWGSC scaffold-based simple sequence repeat (SSR) and two SNP-based semi-thermal asymmetric reverse PCR (STARP) markers were developed for the Sr883-2B region, and one STARP marker was developed for Sr883-6A. Sr883-2B was epistatic to Sr883-6A for reaction to TTKSK and TRTTF, and the two genes had additive effects for TMLKC. These two genes and the markers developed in this research provide additional resources and tools for the improvement in stem rust resistance in durum and common wheat breeding programs.

In Ethiopia, breeding rust resistant wheat cultivars is a priority for wheat production. A stem rust epidemic during 2013 to 2014 on previously resistant cultivar Digalu highlighted the need to determine the effectiveness of wheat lines to multiple races of Puccinia graminis f. sp. tritici in Ethiopia. During 2014 and 2015, we evaluated a total of 97 bread wheat and 14 durum wheat genotypes against four P. graminis f. sp. tritici races at the seedling stage and in single-race field nurseries. Resistance genes were postulated using molecular marker assays. Bread wheat lines were resistant to race JRCQC, the race most virulent to durum wheat. Lines with stem rust resistance gene Sr24 possessed the most effective resistance to the four races. Only three lines with adult plant resistance possessed resistance effective to the four races comparable with cultivars with Sr24. Although responses of the wheat lines across races were positively correlated, wheat lines were identified that possessed adult plant resistance to race TTKSK but were relatively susceptible to race TKTTF. This study demonstrated the importance of testing wheat lines for response to multiple races of the stem rust pathogen to determine if lines possessed non-race-specific resistance. [Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Leaf rust caused by Puccinia triticina Erikss. (Pt) and stem rust caused by Puccinia graminis f. sp. tritici Erikss. & E. Henn (Pgt) are serious constraints to production of durum wheat (Triticum turgidum L). The objective of this study was to identify leaf rust resistance (Lr) and stem rust resistance (Sr) genes/QTL in Portuguese durum landrace PI 192051. Four Pt-isolates, representing three virulence phenotypes (BBBQJ, BBBSJ & EEEEE) and six Pgt-races TTKSK, JRCQC, TKTTF, QFCFC, TPMKC and TMLKC were used to evaluate 180 recombinant inbred lines (RILs) derived from the cross Rusty (rust susceptible) × PI 192051-1 (rust resistant) at the seedling stage. The RILs were also phenotyped at the adult-plant stage in a stem rust nursery in Ethiopia in 2017. The RILs were genotyped using the Illumina iSelect 9K wheat SNP array. PI 192051-1 carries a previously unidentified major Sr gene designated as QSr.ace-7A on chromosome arm 7AS and Lr gene Lr.ace-4A in the pericentromeric region of chromosome 4A. In addition, three minor Sr QTL QSr.ace-1A, QSr.ace-2B and QSr.ace-4A were mapped in PI 192051-1 on chromosomes 1AL, 2BL, and 4A, respectively Lr.ace-4A could be co-located or tightly linked to QSr.ace-4A. Markers linked to the identified QTL/genes can be used for marker assisted selection. These findings enrich the genetic basis of rust resistance in both durum and common wheat.

Dasypyrum villosum is a wild relative of common wheat (Triticum aestivum L.) with resistance to Puccinia graminis f. tritici, the causal agent of stem rust, including the highly virulent race TTKSK (Ug99). In order to transfer resistance, T. durum–D. villosum amphiploids were initially developed and used as a bridge to create wheat–D. villosum introgression lines. Conserved ortholog set (COS) markers were used to identify D. villosum chromosome introgression lines, which were then subjected to seedling P. graminis f. tritici resistance screening with race TTKSK. A COS marker-verified line carrying chromosome 2V with TTKSK resistance was further characterized by combined genomic in situ and fluorescent in situ analyses to confirm a monosomic substitution line MS2V(2D) (20″ + 1′ 2V[2D]). This is the first report of stem rust resistance on 2V, which was temporarily designated as SrTA10276-2V. To facilitate the use of this gene in wheat improvement, a complete set of previously developed wheat–D. villosum disomic addition lines was subjected to genotyping-by-sequencing analysis to develop D. villosum chromosome-specific markers. On average, 350 markers per chromosome were identified. These markers can be used to develop diagnostic markers for D. villosum-derived genes of interest in wheat improvement.

Grain yield is generally the most important criterion growers use to select which cultivar to grow. ‘Shelly’ (Reg. No. CV-1150, PI 681618) hard red spring wheat (Triticum aestivum L.) was released by the University of Minnesota Agricultural Experiment Station in 2016 because it combines very high grain yield with acceptable lodging resistance, grain protein concentration and end-use quality characteristics, and good resistance to the diseases Fusarium head blight, leaf rust, stripe rust, and stem rust. Shelly is a mid-late maturity, semidwarf cultivar that is well adapted to the north-central United States and is among the highest-yielding cultivars currently available.