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Fusarium head blight (FHB), one of the most destructive diseases of wheat in many parts of the world, can reduce the grain quality due to mycotoxin contamination up to rejection for usage as food or feed. Objective of this study was to map quantitative trait loci (QTL) associated with FHB resistance in the winter wheat population ‘G16-92’ (resistant)/‘Hussar’. In all, 136 recombinant inbred lines were evaluated in field trials in 2001 and 2002 after spray inoculation with a Fusarium culmorum suspension. The area under disease progress curve was calculated based on the visually scored FHB symptoms. For means across all environments two FHB resistance QTL located on chromosomes 1A, and 2BL were identified. The individual QTL explained 9.7% and 14.1% of the phenotypic variance and together 26.7% of the genetic variance. The resistance QTL on 1A coincided with a QTL for plant height in contrast to the resistance QTL on 2BL that appeared to be independently inherited from morphological characteristics like plant height and ear compactness. Therefore, especially the QTL on 2BL could be of great interest for breeding towards FHB resistance. [ABSTRACT FROM AUTHOR]

Objective: Acute renal failure remains a major challenge in critical care medicine. Both neutrophils and chemokines have been proposed as key components in the development of acute renal failure. Although the Duffy antigen receptor for chemokines (DARC) is present in several tissues and a highly specific ligand for various chemokines, its exact role in vivo remains unclear.Design: Prospective, controlled experimental study.Setting: University-based research laboratory.Subjects: C57BL/6 wild-type and DARC gene-deficient mice (DARC-/-).Interventions: To unravel the functional relevance of DARC in vivo, we compared wild-type and DARC-/- using neutrophil-dependent models of acute renal failure, induced by either local (renal ischemia-reperfusion) or systemic (endotoxemia, lipopolysaccharide) injury.Measurements and Main Results: Plasma creatinine and blood urea nitrogen concentrations served as indicators of renal function or dysfunction. Enzyme-linked immunosorbent assays were used to measure tissue and plasma chemokine concentrations. We also performed immunostaining to localize chemokine expression and flow cytometry to evaluate neutrophil recruitment into the kidney. Following renal injury, wild-type mice developed moderate renal ischemia-reperfusion(lipopolysaccharide, 300% increase in plasma creatinine concentrations) to severe acute renal failure (renal ischemia-reperfusion, 40% mortality) as well as extensive renal neutrophil recruitment. DARC-/- mice exhibited no renal dysfunction (renal ischemia-reperfusion) or only very mild renal dysfunction (lipopolysaccharide, 20% increase in serum creatinine concentrations). DARC-/- mice showed no postischemic neutrophil infiltration. Although DARC-/- and wild-type mice exhibited similar global renal neutrophil-recruitment during endotoxemia, DARC-/- mice showed significantly impaired neutrophil extravasation. Total renal concentrations of the chemokine macrophage inflammatory protein 2, which has been shown to bind to DARC and to be crucial in postischemic acute renal failure, were either identical (lipopolysaccharide) or only moderately different (renal ischemia-reperfusion) between wild-type and DARC-/- mice. Immunostaining revealed an absence of macrophage inflammatory protein-2 in renal endothelial cells of DARC-/- mice.Conclusions: We suggest that DARC predominantly exerts its effects by controlling spatial chemokine distribution, which in turn regulates neutrophil recruitment and subsequent acute renal failure. [ABSTRACT FROM AUTHOR]

Synthetic wheat lines (2 n = 6 x = 42, AABBDD), which are amphiploids developed from the hybrid between tetraploid wheat ( Triticum turgidum L., 2 n = 4 x = 28, AABB) and Aegilops tauschii Coss. (2 n = 2 x = 14, DD), are important sources of resistance against tan spot of wheat caused by Pyrenophora tritici-repentis. In the present study, inheritance, allelism and genetic linkage analysis in synthetic wheat lines have been carried out. Segregation analysis of the phenotypic and molecular data in F2:3 populations of CS/XX41, CS/XX45, and CS/XX110 has revealed a 1:2:1 segregation ratio indicating that resistance of tan spot in these synthetic lines is controlled by a single gene. Allelism tests detected no segregation for susceptibility among F1 and F2 plants derived from intercrosses of the resistance lines XX41, XX45 and XX110 indicating that the genes are either allelic or tightly linked. Linkage analysis using SSR markers showed that all the three genes: tsn3a in XX41, Tsn3b in XX45 and tsn3c in XX110 are clustered in the region around Xgwm2a, located on the short arm of chromosome 3D. The linked markers and genetic relationship of these genes will greatly facilitate their use in wheat breeding and deployment of cultivars resistant to tan spot. [ABSTRACT FROM AUTHOR]

Fusarium head blight (FHB), mainly caused by Fusarium graminearum and F. culmorum, can significantly reduce the grain quality of wheat ( Triticum aestivum L.) due to mycotoxin contamination. The objective of this study was to identify quantitative trait loci (QTLs) for FHB resistance in a winter wheat population developed by crossing the resistant German cultivar Dream with the susceptible British cultivar Lynx. A total of 145 recombinant inbred lines (RILs) were evaluated following spray inoculation with a F. culmorum suspension in field trials in 2002 in four environments across Germany. Based on amplified fragment length polymorphism and simple sequence repeat marker data, a 1,734 cM linkage map was established assuming that the majority of the polymorphic parts of the genome were covered. The area under disease progress curve (AUDPC) was calculated based on the visually scored FHB symptoms. The population segregated quantitatively for FHB severity. Composite interval mapping analysis for means across the environments identified four FHB resistance QTLs on chromosomes 6AL, 1B, 2BL and 7BS. Individually the QTLs explained 19%, 12%, 11% and 21% of the phenotypic variance, respectively, and together accounted for 41%. The QTL alleles conferring resistance on 6AL, 2BL and 7BS originated from cv. Dream. The resistance QTL on chromosome 6AL partly overlapped with a QTL for plant height. The FHB resistance QTL on 7BS coincided with a QTL for heading date, but the additive effect on heading date was of minor importance. The resistance QTL on chromosome 1B was associated with the T1BL.1RS wheat-rye translocation of Lynx. [ABSTRACT FROM AUTHOR]

A significant association between CSF Aβ42 and cognition in patients with Alzheimer’s disease (AD) homozygous for the ∊3 allele of the apolipoprotein E (apoE) has been described. In this study we extended our observations on apoE, as another plaque component, and investigated the association between CSF apoE concentrations and cognitive performance after stratification for the apoE genotype in 62 patients with AD, 19 other forms of dementia and 18 controls. CSF Aβ42 and apoE concentrations were significantly and positively associated with Mini Mental State Examination (MMSE) score in AD (Aβ42: r = 0.332; P = 0.026; apoE: r = 0.386; P = 0.006). For Aβ42 this association was exclusively present in ∊3 homozygotes (r = 0.44; P = 0.014), whereas apoE was correlated with MMSE in ∊4 hetero- or homozygotes subjects (∊4/∊X: r = 0.638; P = 0.004: ∊4/∊4; r = 0.812; P = 0.05). No association was observed between CSF concentrations of Aβ42 and apoE. The significant relationship between MMSE and CSF Aβ42 in ∊3 homozygotes and apoE in ∊4 hetero- and homozygotes respectively may suggest that both proteins may be associated independently from each other with cognitive decline. [Copyright &y& Elsevier]

Introduction: Cytosolic pattern recognition receptors (PRR) have been shown to detect nucleic acids from RNA and DNA viruses in order to launch a type I interferon mediated antiviral state . Here we show that RNA of the facultative intracellular bacterium Salmonella typhimurium is a ligand for RIG-I, triggers production of type-I interferons and contributes to pathogenicity in vivo. Methods: We use RIG-I−/− MEFs or human epithelial cells depleted of RIG-I by lentiviral shRNA transduction for transfection and infection experiments. IFNbeta production was measured by 293T IFNbeta- reporter cells or qPCR. Intracellular bacterial titers were determined by gentamycin protection assay. In vivo infection experiments were performed as described using SL1344 or SL1344 aroA deficient Salmonella strains in RIG-I+/+ and RIG-I−/− mice . Results: Infection of fibroblasts and epithelial cells with S. typhimurium, but not with non-invasive E. coli, triggers IFNbeta transcription, suggesting that intracellular replication is required. RIG-I dependent recognition of bacterial RNA is dominant in non-phagocytic cells, as shown in RIG-I knockout and knockdown model cells. Despite presence of other pathogen-associated patterns (PAMP), like LPS or flagellin, no IFNbeta was produced in fibroblasts and epithelial cells lacking RIG-I upon S. typhimurium infection. In contrast, in macrophages TLR dependent recognition of bacterial PAMPs through TRIF/Myd88 overcomes RIG-I deficiency and leads to robust induction of type I interferon. We observed higher bacterial titers at early time points after infection in the cecum of S. typhimurium infected RIG-I−/− mice, when compared to wild type animals. However, at later stages of infection, S. typhimurium overcomes the innate response leading to similar weight loss and mortality in wildtype and RIG-I−/− mice. Conclusion: In summary, our data implicate a role of RIG-I mediated innate immune recognition of bacterial RNA in early control of bacterial replication, most likely mediated by non-phagocytic intestinal epithelial cells targeted by S. typhimurium. [Copyright &y& Elsevier]

Abstract: Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses. [Copyright &y& Elsevier]

During 2 years and at five locations in Europe, 56 winter wheat genotypes were evaluated for resistance to Fusarium head blight (FHB). The genotypes were both parents and selected recombinants taken from the following populations previously tested for FHB resistance: ‘Arina’/‘Forno’, ‘Arina’/‘Riband’, ‘Dream’/‘Lynx’, G16-92/‘Hussar’, ‘Renan’/‘Récital’, SVP-72017 × ‘Capo’ and ‘Capo’/‘Sumai-3’. In addition, a few control lines were included. FHB resistance was evaluated in replicated experiments under artificial inoculation, disease severity was assessed by repeated visual scorings. The highest level of FHB resistance was found in lines selected from crosses of FHB-resistant winter wheat × ‘Sumai-3’. The best lines selected from crosses of moderately resistant winter wheat with susceptible winter wheat were similar in their resistance response to the resistant parent. The level of FHB resistance was correlated with stability of resistance. Susceptible wheat lines tended to exhibit severe symptoms under high disease pressure. The symptoms on resistant lines remained comparatively low even under high disease pressure. [ABSTRACT FROM AUTHOR]

CD8+ cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of antigen cross-presentation by DCs to the induction of anti-viral cytotoxic T cells remains controversial. Here, we used a recombinant influenza virus expressing a nonstructural 1-GFP (NS1-GFP) reporter gene to visualize the route of antigen presentation by lung DCs upon viral infection in mice. We found that lung CD103+ DCs were the only subset of cells that carried intact GFP protein to the draining LNs. Strikingly, lung migratory CD103+ DCs were not productively infected by influenza virus and thus were able to induce virus-specific CD8+ T cells through the cross-presentation of antigens from virally infected cells. We also observed that CD103+ DC resistance to infection correlates with an increased anti-viral state in these cells that is dependent on the expression of type I IFN receptor. These results show that efficient cross-priming by migratory lung DCs is coupled to the acquisition of an anti-viral status, which is dependent on the type I IFN signaling pathway. [ABSTRACT FROM AUTHOR]

Patients with systemic lupus erythematosus (SLE) often develop a wide variety of serological manifestations including the presence of antibodies to double-stranded DNA (anti-dsDNA). Positivity for anti-dsDNA constitutes one of the laboratory criteria for the diagnosis of SLE and is therefore clinically relevant. We analyzed the diagnostic accuracies of four commercial anti-dsDNA immunoassays and compared the results with a recently established surface plasmon resonance (SPR) biosensor chip with covalently chip-immobilized dsDNA. The anti-dsDNA measurements were performed retrospectively in 50 patients with clinically proven SLE, 39 patients with other autoimmunopathies and 20 healthy controls. Data were evaluated by Receiver-Operator Characteristic (ROC) analysis, with special regard to SLE patients suffering from lupus nephritis. The ROC analyses for the four immunoassays and the SPR biosensor resulted in the following area-under-the-curve (AUC) and diagnostic efficiency (DE) values in descending order: Bindazyme AUC, 0.89; DE, 0.88; ELiA AUC, 0.89; DE, 0.86; SPR biosensor AUC, 0.82; DE, 0.80; Farrzyme AUC, 0.77; DE, 0.77; Farr AUC, 0.77; DE, 0.70. When considering the 22 nephritis SLE patients the following AUC were observed: Bindazyme 0.98; EliA 0.95; SPR biosensor 0.93; Farr 0.89; Farrzyme 0.88. Although various methodologies for the determination of anti-dsDNA were compared, the overall diagnostic accuracy was found satisfactory in all immunoassays. Best data were found for the Bindazyme assay. We referenced the measurements to our in-house SPR biosensor device which showed good AUC and DE values. When optimized, this technique, allowing to monitor antigen/ antibody interactions in real-time, may add a new analytical quality to the existing methods, potentially beneficial in diagnosis and clinical monitoring of SLE. [ABSTRACT FROM AUTHOR]

Fusarium head blight (FHB) is one of the most important wheat diseases that causes yield and quality losses as well as contamination with deoxynivalenol (DON). This study aimed for marker-based introduction of three previously mapped QTLs from two German winter wheat resistance sources into an elite background unrelated to the mapping population. A double cross (DC) served as initial population that combined two resistance donor-QTL alleles from “Dream” ( Qfhs.lfl-6AL, Qfhs.lfl-7BS) and one donor-QTL allele from “G16-92” on chromosome 2BL with two high yielding, susceptible elite winter wheats (“Brando”, “LP235.1”). The initial population of 600 DC-derived F1 lines was selected with SSR markers for the respective QTLs. After two marker-selection steps, each of eight marker classes was represented by 9–22 lines possessing the respective donor-QTL allele or all possible combinations thereof in the homozygous state. The effect of the QTLs was estimated by field tests at four locations inoculated with Fusarium culmorum. Resistance was measured as the mean of multiple FHB ratings (0–100%). Marker classes incorporating only one QTL were not significantly more resistant than the class without any QTL, the combination of two donor-QTL alleles reduced FHB significantly. On average, lines with Qfhs.lfl-6AL were significantly taller than lines without this QTL. A considerable variation for FHB resistance was found in all marker classes. Marker-based introduction of two QTLs enhanced mean FHB rating by about 40 percentage points, the selected plants, however, were, on average, significantly taller. Both findings strongly support a phenotypic selection following after marker-based introduction of effective QTLs. [ABSTRACT FROM AUTHOR]

Objective: To compare the interexaminer and the intraexaminer reliability of measuring passive flexion and extension ranges of motion of the cervical spine, using a Cybex 320 EDI (inclinometer) and a Cervical Range of Motion (CROM) instrument. Design: Blind, repeated measures of passive cervical flexion, extension range of motion by three different examiners. Setting: Private multi-disciplinary clinic. Participants: 27 volunteers, varying from asymptomatic to symptomatic conditions of the cervical spine, 14 males and 13 females, aged 10-67 years. Intervention: Measurement of passive cervical flexion, extension range of motion using the Cybex 320 EDI (single inclinometer) and the CROM by three blinded examiners, following the protocol in the respective manufacturers' manuals. The three examiners assessed each of the 27 subjects twice on each instrumentfor flexion and extension. Results: The intraexaminer reliability for both the CROM and the Cybex 320 EDI were high, 95% confidence interval ICC values of .96-.99 and .85-.96 were found for the CROM and the Cybex 320 EDI instruments, respectively. The average (standard deviation) range of motion between the CROM and the Cybex 320 EDI for flexion was found to be 49.5 (15.3) and 53.9 (17.5) and extension 62.9 (22.6) and 43.6 (16.7), respectively. The interexaminer reliability analyses also showed high correlations (ICC 95% CI = .96- .97, ICC 95% CI = .80- .89)for the CROM and Cybex 320 EDI, respectively. Conclusion: Range of motion determination is an integral component of an individual's assessment when the cervical spine is in question. Choosing the most appropriate instrument and matching the choice to the parameters of the individual venue, considering, i.e. cost-effectiveness for assessment, and quality makes our result findings informative and pertinent. While both instruments yielded clinically acceptable intraexaminer and interexaminer agreement, relevant to practitioners treating injured persons, the CROM was found to have a higher reliability for cervical passive range of motion when evaluating passive flexion and extension. [ABSTRACT FROM AUTHOR]