[Meatal and glandular urethral strictures]. / Meatusenge und glanduläre Harnröhrenstriktur.

Distal urethral strictures comprise meatal or glandular stenoses and occur due to trauma, iatrogenic instrumentalization, infection, skin diseases such as lichen sclerosus or idiopathically. Given that 18% of anterior strictures (bulbar, penile, or glandular) are located in the very distal part, meatal/glandular stricture disease represents a non-negligible subgroup among all urethral strictures. The prevalence within Western industrialized countries is estimated to be approximately 0.6-0.9%, which translates into a total of 250,000 men being affected in Germany. Without any therapy, there is a severe risk of functional damage to the kidneys and the remaining urinary tract as well as significant reduction of quality of life. The therapeutic success of regaining sufficient micturition and a satisfying cosmetic result can only be obtained by means of surgical intervention. Besides dilatation and urethrotomy, preferably a single or multiple staged open urethroplasty with transplantation of autogenous genital or non-genital tissue can be performed. The choice of the appropriate surgical concept depends on stricture etiology, comorbidity status, and the patient's compliance. In case of histologically diagnosed lichen sclerosus, the use of genital skin should be avoided. To date, there are no universally accepted recommendations regarding the optimal use of substitution techniques. However, the use of oral mucosal tissue grafts seem to be the most promising, given low recurrence rates, and thus can be considered as the current gold standard.

Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels.

BACKGROUND: Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders. METHODS AND RESULTS: To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By genome-wide association study, we confirmed association of IL-18 levels with a single nucleotide polymorphism in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, caspase recruitment domain-containing 4) gene on chromosome 2 (rs385076; P=2.4 × 10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. CONCLUSIONS: Our study provides evidence for the functional causality of single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation.

Mixtures of genetically modified wheat lines outperform monocultures.

Biodiversity research shows that diverse plant communities are more stable and productive than monocultures. Similarly, populations in which genotypes with different pathogen resistance are mixed may have lower pathogen levels and thus higher productivity than genetically uniform populations. We used genetically modified (GM) wheat as a model system to test this prediction, because it allowed us to use genotypes that differed only in the trait pathogen resistance but were otherwise identical. We grew three such genotypes or lines in monocultures or two-line mixtures. Phenotypic measurements were taken at the level of individual plants and of entire plots (population level). We found that resistance to mildew increased with both GM richness (0, 1, or 2 Pm3 transgenes with different resistance specificities per plot) and GM concentration (0%, 50%, or 100% of all plants in a plot with a Pm3 transgene). Plots with two transgenes had 34.6% less mildew infection and as a consequence 7.3% higher seed yield than plots with one transgene. We conclude that combining genetic modification with mixed cropping techniques could be a promising approach to increase sustainability and productivity in agricultural systems, as the fitness cost of stacking transgenes within individuals may thus be avoided.

Competitive performance of transgenic wheat resistant to powdery mildew.

Genetically modified (GM) plants offer an ideal model system to study the influence of single genes that confer constitutive resistance to pathogens on the ecological behaviour of plants. We used phytometers to study competitive interactions between GM lines of spring wheat Triticum aestivum carrying such genes and control lines. We hypothesized that competitive performance of GM lines would be reduced due to enhanced transgene expression under pathogen levels typically encountered in the field. The transgenes pm3b from wheat (resistance against powdery mildew Blumeria graminis) or chitinase and glucanase genes from barley (resistance against fungi in general) were introduced with the ubiquitin promoter from maize (pm3b and chitinase genes) or the actin promoter from rice (glucanase gene). Phytometers of 15 transgenic and non-transgenic wheat lines were transplanted as seedlings into plots sown with the same 15 lines as competitive environments and subject to two soil nutrient levels. Pm3b lines had reduced mildew incidence compared with control lines. Chitinase and chitinase/glucanase lines showed the same high resistance to mildew as their control in low-nutrient treatment and slightly lower mildew rates than the control in high-nutrient environment. Pm3b lines were weaker competitors than control lines. This resulted in reduced yield and seed number. The Pm3b line with the highest transgene expression had 53.2% lower yield than the control whereas the Pm3b line which segregated in resistance and had higher mildew rates showed only minor costs under competition. The line expressing both chitinase and glucanase genes also showed reduced yield and seed number under competition compared with its control. Our results suggest that single transgenes conferring constitutive resistance to pathogens can have ecological costs and can weaken plant competitiveness even in the presence of the pathogen. The magnitude of these costs appears related to the degree of expression of the transgenes.

Transgenic Pm3b wheat lines show resistance to powdery mildew in the field.

Plant resistance (R) genes are highly effective in protecting plants against diseases, but pathogens can overcome such genes relatively easily by adaptation. Consequently, in many cases R genes do not confer durable resistance in agricultural environments. One possible strategy to make the use of R genes more sustainable depends on the modification of R genes followed by transformation. To test a possible transgenic use of R genes, we overexpressed in wheat the Pm3b resistance gene against powdery mildew under control of the maize ubiquitin promoter. Four independent transgenic lines were tested in the greenhouse and the field during 3 years. The four lines showed a five- to 600-fold transgene overexpression compared with the expression of the endogenous Pm3b gene in the landrace 'Chul'. Powdery mildew resistance was significantly improved in all lines in the greenhouse and the field, both with naturally occurring infection or after artificial inoculation. Under controlled environmental conditions, the line with the strongest overexpression of the Pm3b gene showed a dramatic increase in resistance to powdery mildew isolates that are virulent on the endogenous Pm3b. Under a variety of field conditions, but never in the greenhouse, three of the four transgenic lines showed pleiotropic effects on spike and leaf morphology. The highest overexpressing line had the strongest side effects, suggesting a correlation between expression level and phenotypic changes. These results demonstrate that the successful transgenic use of R genes critically depends on achieving an optimal level of their expression, possibly in a tissue-specific way.

Gene flow in genetically modified wheat.

Understanding gene flow in genetically modified (GM) crops is critical to answering questions regarding risk-assessment and the coexistence of GM and non-GM crops. In two field experiments, we tested whether rates of cross-pollination differed between GM and non-GM lines of the predominantly self-pollinating wheat Triticum aestivum. In the first experiment, outcrossing was studied within the field by planting "phytometers" of one line into stands of another line. In the second experiment, outcrossing was studied over distances of 0.5-2.5 m from a central patch of pollen donors to adjacent patches of pollen recipients. Cross-pollination and outcrossing was detected when offspring of a pollen recipient without a particular transgene contained this transgene in heterozygous condition. The GM lines had been produced from the varieties Bobwhite or Frisal and contained Pm3b or chitinase/glucanase transgenes, respectively, in homozygous condition. These transgenes increase plant resistance against pathogenic fungi. Although the overall outcrossing rate in the first experiment was only 3.4%, Bobwhite GM lines containing the Pm3b transgene were six times more likely than non-GM control lines to produce outcrossed offspring. There was additional variation in outcrossing rate among the four GM-lines, presumably due to the different transgene insertion events. Among the pollen donors, the Frisal GM line expressing a chitinase transgene caused more outcrossing than the GM line expressing both a chitinase and a glucanase transgene. In the second experiment, outcrossing after cross-pollination declined from 0.7-0.03% over the test distances of 0.5-2.5 m. Our results suggest that pollen-mediated gene flow between GM and non-GM wheat might only be a concern if it occurs within fields, e.g. due to seed contamination. Methodologically our study demonstrates that outcrossing rates between transgenic and other lines within crops can be assessed using a phytometer approach and that gene-flow distances can be efficiently estimated with population-level PCR analyses.

Transgene x environment interactions in genetically modified wheat.

BACKGROUND: The introduction of transgenes into plants may cause unintended phenotypic effects which could have an impact on the plant itself and the environment. Little is published in the scientific literature about the interrelation of environmental factors and possible unintended effects in genetically modified (GM) plants. METHODS AND FINDINGS: We studied transgenic bread wheat Triticum aestivum lines expressing the wheat Pm3b gene against the fungus powdery mildew Blumeria graminis f.sp. tritici. Four independent offspring pairs, each consisting of a GM line and its corresponding non-GM control line, were grown under different soil nutrient conditions and with and without fungicide treatment in the glasshouse. Furthermore, we performed a field experiment with a similar design to validate our glasshouse results. The transgene increased the resistance to powdery mildew in all environments. However, GM plants reacted sensitive to fungicide spraying in the glasshouse. Without fungicide treatment, in the glasshouse GM lines had increased vegetative biomass and seed number and a twofold yield compared with control lines. In the field these results were reversed. Fertilization generally increased GM/control differences in the glasshouse but not in the field. Two of four GM lines showed up to 56% yield reduction and a 40-fold increase of infection with ergot disease Claviceps purpurea compared with their control lines in the field experiment; one GM line was very similar to its control. CONCLUSIONS: Our results demonstrate that, depending on the insertion event, a particular transgene can have large effects on the entire phenotype of a plant and that these effects can sometimes be reversed when plants are moved from the glasshouse to the field. However, it remains unclear which mechanisms underlie these effects and how they may affect concepts in molecular plant breeding and plant evolutionary ecology.

Broad multiwavelength source with 50 GHz channel spacing for wavelength division multiplexing applications in the telecom C band.

We present a multiwavelength source with a spectral width of 42 nm at -20 dB. The frequency comb is generated by spectrally broadening the output of an amplified 50 GHz Er:Yb:glass laser with a highly nonlinear photonic crystal fiber. After spectral flattening the comb covers 37 channels with 5.4 mW average power per channel, and locking only one central wavelength channel to the International Telecommunication Union grid results in a maximum frequency error of 0.24% for all channels.

Host-plant selectivity of rhizobacteria in a crop/weed model system.

Belowground microorganisms are known to influence plants' performance by altering the soil environment. Plant pathogens such as cyanide-producing strains of the rhizobacterium Pseudomonas may show strong host-plant selectivity. We analyzed interactions between different host plants and Pseudomonas strains and tested if these can be linked to the cyanide sensitivity of host plants, the cyanide production of bacterial strains or the plant identity from which strains had been isolated. Eight strains (four cyanide producing) were isolated from roots of four weed species and then re-inoculated on the four weed and two additional crop species. Bacterial strain composition varied strongly among the four weed species. Although all six plant species showed different reductions in root growth when cyanide was artificially applied to seedlings, they were generally not negatively affected by inoculation with cyanide-producing bacterial strains. We found a highly significant plant species x bacterial strain interaction. Partitioning this interaction into contrasts showed that it was entirely due to a strongly negative effect of a bacterial strain (Pseudomonas kilonensis/brassicacearum, isolated from Galium mollugo) on Echinochloa crus-galli. This exotic weed may not have become adapted to the bacterial strain isolated from a native weed. Our findings suggest that host-specific rhizobacteria hold some promise as biological weed-control agents.