Quantitative trait loci for adult-plant resistance to Mycosphaerella graminicola in two winter wheat populations.

Septoria tritici blotch (STB) is one of the most important leaf spot diseases in wheat worldwide. The goal of this study was to detect chromosomal regions for adult-plant resistance in large winter wheat populations to STB. Inoculation by two isolates with virulence to Stb6 and Stb15, both present in the parents, was performed and STB severity was visually scored plotwise as percent coverage of flag leaves with pycnidia-bearing lesions. 'Florett'/'Biscay' and 'Tuareg'/'Biscay', each comprising a cross of a resistant and a susceptible cultivar, with population sizes of 316 and 269 F(7:8) recombinant inbred lines, respectively, were phenotyped across four and five environments and mapped with amplified fragment length polymorphism, diversity array technology, and simple sequence repeat markers covering polymorphic regions of ≈1,340 centimorgans. Phenotypic data revealed significant (P < 0.01) genotypic differentiation for STB, heading date, and plant height. Entry-mean heritabilities (h(2)) for STB were 0.73 for 'Florett'/'Biscay' and 0.38 for 'Tuareg'/'Biscay'. All correlations between STB and heading date as well as between STB and plant height were low (r = -0.13 to -0.20). In quantitative trait loci (QTL) analysis, nine and six QTL were found for STB ratings explaining, together, 55 and 51% of phenotypic variation in 'Florett'/'Biscay' and 'Tuareg'/'Biscay', respectively. Genotype-environment and QTL-environment interactions had a large impact. Two major QTL were detected consistently across environments on chromosomes 3B and 6D from 'Florett' and chromosomes 4B and 6B from 'Tuareg', each explaining 12 to 17% of normalized adjusted phenotypic variance. These results indicate that adult-plant resistance to STB in both mapping populations was of a quantitative nature.

Current Status of Companion and Complementary Diagnostics: Strategic Considerations for Development and Launch.

US Food and Drug Administration (FDA)-approved diagnostic assays play an increasingly common role in managing patients to prolong lifespan while also enhancing quality of life. Diagnostic assays can be essential for the safe and effective use of therapeutics (companion diagnostic), or may inform on improving the benefit/risk ratio without restricting drug access (complementary diagnostic). This tutorial reviews strategic considerations for drug and assay development resulting in FDA-approved companion or complementary diagnostic status.

Impact of management practices on the tallgrass prairie.

The ELM ecosystem-level grassland model simulates the flow of water, heat, nitrogen, and phosphorus through the ecosystem and the biomass dynamics of plants, consumers, and the decomposers. This model was adapted to a tallgrass prairie site in northeastern Oklahoma, USA, the Osage Site of the U.S. International Biological Program Grassland Biome. Several range management manipulations were simulated by the model and the results compared to field data and literature information: (1) altering the grazing intensity, grazing system, and grazing time period; (2) adding nitrogen and phosphorus to the grassland; (3) adding water during the growing season; and (4) spring burning of the prairie.The model showed that cattle weight gain per head, above-ground and belowground plant production, transpiration water loss, standing dead biomass, and the net nitrogen balance decrease with increasing grazing intensity, while soil water content and bare soil water loss increase. A moderately stocked year-round cow-calf grazing system is more beneficial to the grassland than a more highly stocked seasonal steer grazing system because the former increases the aboveground and belowground primary production and the plant nutrient uptake rates. Range manipulations, such as fire, which stimulate uniform grazing of a pasture, increase primary production, cattle weight gains, and nutrient uptake of plants and animals. Model results indicated that adding fertilizer was the best strategy for increasing cattle weight gains per head, while adding water would produce the greatest increase in primary production. Simulation of yearly and triennial spring burns suggests that these treatments increase primary production, plant nutrient uptake, and cattle weight gain per head. Burning increases the nitrogen losses from the systems; however, these losses are greater with annual burns. The model results also suggest the spatial grazing pattern of cattle must be considered to correctly represent the impact of grazing on the prairie.The model is used to describe the behavior of the tallgrass prairie ecosystem, evaluate alternative management strategies, and identify future scientific research and management studies.

IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp.

IL-18, or IGIF (interferon-gamma inducing factor), is an IL-1-related, pro-inflammatory cytokine, which plays a pivotal role in systemic and local inflammation. We have identified and characterized IL-1H, a novel IL-1-related molecule. IL-1H appears to be expressed in most tissues with relatively high levels in testis, thymus and uterus. The IL-1H transcripts were stimulated by phorbol ester (PMA) in human cell lines (A431, THP-1 and KG-1) and peripheral blood mononuclear cells (HPBMC) and dendritic cells (NHDC). The protein sequence of IL-1H is mostly related to IL-1ra with a similarity of 36%. A short form of IL-1H was identified, and lacks a 40-amino acid segment in the amino-terminal region of the protein. When expressed in mammalian cells, two secreted polypeptides of IL-1H were identified: an uncleaved and a cleaved form starting with amino acid Val-46. Furthermore, IL-1H binds the IL-18 receptor, but not the IL-1 receptor. These findings suggest that IL-1H may be another ligand for the IL-18 receptor and a new player in the inflammatory and immune responses mediated by the IL-18/IL-18R axis.

Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice.

IL-17 is a proinflammatory cytokine, and its in vivo expression induces neutrophilia in mice. IL-17E is a recently described member of an emerging family of IL-17-related cytokines. IL-17E has been shown to bind IL-17Rh1, a protein distantly related to the IL-17R, suggesting that IL-17E probably possesses unique biological functions. In this study, we have identified the murine ortholog of IL-17E and developed transgenic mice to characterize its actions in vivo. Biological consequences of overexpression of murine (m)IL-17E, both unique to IL-17E and similar to IL-17, were revealed. Exposure to mIL-17E resulted in a Th2-biased response, characterized by eosinophilia, increased serum IgE and IgG1, and a Th2 cytokine profile including elevated serum levels of IL-13 and IL-5 and elevated gene expression of IL-4, IL-5, IL-10, and IL-13 was observed in many tissues. Increased gene expression of IFN-gamma in several tissues and elevated serum TNF-alpha were also noted. In addition, IL-17E induces G-CSF production in vitro and mIL-17E-transgenic mice had increased serum G-CSF and exhibit neutrophilia, a property shared by IL-17. Moreover, exposure to mIL-17E elicited pathological changes in multiple tissues, particularly liver, heart, and lungs, characterized by mixed inflammatory cell infiltration, epithelial hyperplasia, and hypertrophy. Taken together, these findings suggest that IL-17E is a unique pleiotropic cytokine and may be an important mediator of inflammatory and immune responses.

IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding.

The proinflammatory cytokine interleukin 17 (IL-17) is the founding member of a family of secreted proteins that elicit potent cellular responses. We report a novel human IL-17 homolog, IL-17F, and show that it is expressed by activated T cells, can stimulate production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Unexpectedly, the crystal structure of IL-17F reveals that IL-17 family members adopt a monomer fold typical of cystine knot growth factors, despite lacking the disulfide responsible for defining the canonical "knot" structure. IL-17F dimerizes in a parallel manner like neurotrophins, and features an unusually large cavity on its surface. Remarkably, this cavity is located in precisely the same position where nerve growth factor binds its high affinity receptor, TrkA, suggesting further parallels between IL-17s and neurotrophins with respect to receptor recognition.