Characterisation of barley resistance to rhynchosporium on chromosome 6HS

Key Message: Major resistance gene to rhynchosporium, Rrs18, maps close to the telomere on the short arm of chromosome 6H in barley. Rhynchosporium or barley scald caused by a fungal pathogen Rhynchosporium commune is one of the most destructive and economically important diseases of barley in the world. Testing of Steptoe × Morex and CIho 3515 × Alexis doubled haploid populations has revealed a large effect QTL for resistance to R. commune close to the telomere on the short arm of chromosome 6H, present in both populations. Mapping markers flanking the QTL from both populations onto the 2017 Morex genome assembly revealed a rhynchosporium resistance locus independent of Rrs13 that we named Rrs18. The causal gene was fine mapped to an interval of 660 Kb using Steptoe × Morex backcross 1 S₂ and S₃ lines with molecular markers developed from Steptoe exome capture variant calling. Sequencing RNA from CIho 3515 and Alexis revealed that only 4 genes within the Rrs18 interval were transcribed in leaf tissue with a serine/threonine protein kinase being the most likely candidate for Rrs18.Max Coulter, Bianca Büttner, Kerstin Hofmann, Micha Bayer, Luke Ramsay, Günther Schweizer, Robbie Waugh, Mark E. Looseley, Anna Avrov

A Unique Carrier for Delivery of Therapeutic Compounds beyond the Blood-Brain Barrier

BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB) that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin), across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX) or adriamycin (ADR) and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders, including classes of resident and metastatic brain tumors. It may be prudent, therefore, to consider implementation of this novel delivery platform in various clinical settings for therapeutic intervention in acute and chronic neurological diseases

Differential remodeling in small and large murine airways revealed by novel whole lung airway analysis.

Airway remodeling occurs in chronic asthma leading to increased airway smooth muscle (ASM) mass and extracellular matrix (ECM) deposition. Although extensively studied in murine airways, studies report only selected larger airways at one time-point meaning the spatial distribution and resolution of remodeling are poorly understood. Here we use a new method allowing comprehensive assessment of the spatial and temporal changes in ASM, ECM, and epithelium in large numbers of murine airways after allergen challenge. Using image processing to analyze 20-50 airways per mouse from a whole lung section revealed increases in ASM and ECM after allergen challenge were greater in small and large rather than intermediate airways. ASM predominantly accumulated adjacent to the basement membrane, whereas ECM was distributed across the airway wall. Epithelial hyperplasia was most marked in small and intermediate airways. After challenge, ASM changes resolved over 7 days, whereas ECM and epithelial changes persisted. The new method suggests large and small airways remodel differently, and the long-term consequences of airway inflammation may depend more on ECM and epithelial changes than ASM. The improved quantity and quality of unbiased data provided by the method reveals important spatial differences in remodeling and could set new analysis standards for murine asthma models

Crossover equation of state models applied to the critical behavior of Xenon

The turbidity ( τ ) measurements of Güttinger and Cannell (Phys Rev A 24:3188–3201, 1981) in the temperature range 28mK≤T−Tc≤29K along the critical isochore of homogeneous xenon are reanalyzed. The singular behaviors of the isothermal compressibility ( κT ) and the correlation length ( ξ ) predicted from the master crossover functions are introduced in the turbidity functional form derived by Puglielli and Ford (Phys Rev Lett 25:143–146, 1970). We show that the turbidity data are thus well represented by the Ornstein–Zernike approximant, within 1 % precision. We also introduce a new crossover master model (CMM) of the parametric equation of state for a simple fluid system with no adjustable parameter. The CMM model and the phenomenological crossover parametric model are compared with the turbidity data and the coexisting liquid–gas density difference ( ΔρLV ). The excellent agreement observed for τ , κT , ξ , and ΔρLV in a finite temperature range well beyond the Ising-like preasymptotic domain confirms that the Ising-like critical crossover behavior of xenon can be described in conformity with the universal features estimated by the renormalization-group methods. Only 4 critical coordinates of the vapor–liquid critical point are needed in the (pressure, temperature, molecular volume) phase surface of xenon

Fine mapping of the Rrs1 resistance locus against scald in two large populations derived from Spanish barley landraces

Key messageIn two Spanish barley landraces with outstanding resistance to scald, the Rrs1 Rh4 locus was fine mapped including all known markers used in previous studies and closely linked markers were developed. Scald, caused by Rhynchosporium commune, is one of the most prevalent barley diseases worldwide. A search for new resistance sources revealed that Spanish landrace-derived lines SBCC145 and SBCC154 showed outstanding resistance to scald. They were crossed to susceptible cultivar Beatrix to create large DH-mapping populations of 522 and 416 DH lines that were scored for disease resistance in the greenhouse using two R. commune isolates. To ascertain the pattern of resistance, parents and reference barley lines with known scald resistance were phenotyped with a panel of differential R. commune isolates. Subpopulations were genotyped with the Illumina GoldenGate 1,536 SNP Assay and a large QTL in the centromeric region of chromosome 3H, known to harbour several scald resistance genes and/or alleles, was found in both populations. Five SNP markers closest to the QTL were converted into CAPS markers. These CAPS markers, together with informative SSR markers used in other scald studies, confirmed the presence of the Rrs1 locus. The panel of differential scald isolates indicated that the allele carried by both donors was Rrs1 Rh4 . The genetic distance between Rrs1 and its flanking markers was 1.2 cM (11_0010) proximally and 0.9 cM (11_0823) distally, which corresponds to a distance of just below 9 Mbp. The number and nature of scald resistance genes on chromosome 3H are discussed. The effective Rrs1 allele found and the closely linked markers developed are already useful tools for molecular breeding programs and provide a good step towards the identification of candidate genes.Kerstin Hofmann, Cristina Silvar, Ana M. Casas, Markus Herz, Bianca Büttner, M. Pilar Gracia, Bruno Contreras‑Moreira, Hugh Wallwork, Ernesto Igartua, Günther Schweize

Designing a Serious Game for Youth with ASD: Perspectives from End-Users and Professionals

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Recent years have seen an emergence of social emotional computer games for individuals with Autism Spectrum Disorder (ASD). These games are heterogeneous in design with few underpinned by theoretically informed approaches to computer-based interventions. Guided by the serious game framework outlined by Whyte et al. (Journal of Autism and Developmental Disorders 45(12):1–12, 2014), this study aimed to identify the key motivating and learning features for serious games targeting emotion recognition skills from the perspectives of 11 youth with ASD and 11 experienced professionals. Results demonstrated that youth emphasised the motivating aspects of game design, while the professionals stressed embedding elements facilitating the generalisation of acquired skills. Both complementary and differing views provide suggestions for the application of serious game principles in a potential serious game