Phenotyping at hot spots and tagging of QTLs conferring spot blotch resistance in bread wheat.

Spot blotch is a major foliar disease of wheat caused by Bipolaris sorokiniana in warm and humid environments of the world including South Asian countries. In India, it has a larger impact in Indo-Gangetic plains of the country. Therefore, the present study was undertaken to phenotype a mapping population at different hot spots of India and to detect quantitative trait loci (QTL) for resistance to spot blotch in wheat. For this study, 209 single seed descent (SSD) derived F8, F9, F10 recombinant inbred lines (RILs) of the cross 'Sonalika' (an Indian susceptible cultivar)/'BH 1146' (a Brazilian resistant cultivar) were assessed for spot blotch resistance at two hot spot locations (Coochbehar and Kalyani) for three years and for two years under controlled conditions in the polyhouse (Karnal). The population showed large variation in spot blotch reaction for disease severity in all the environments indicating polygenic nature of the disease. Microsatellite markers were used to create the linkage maps. Joint and/or individual year analysis by composite interval mapping (CIM) and likelihood of odds ratio (LOD) >2.1, detected two consistent QTLs mapped on chromosome 7BL and 7DL and these explained phenotypic variation of 11.4 percent and 9.5 percent over the years and locations, respectively. The resistance at these loci was contributed by the parent 'BH 1146' and shown to be independent of plant height and earliness. Besides, association of some agro-morphological traits has also been observed with percent disease severity. These identified genomic regions may be used in future wheat breeding programs through marker assisted selection for developing spot blotch resistant cultivars.

In vivo quantification of serotonin transporters using [(11)C]DASB and positron emission tomography in humans: modeling considerations.

Positron emission tomography (PET) studies of the serotonin transporter (5-HTT) in the human brain are increasingly using the radioligand [(11)C]N, N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine. A variety of models have been applied to such data in several published articles; however to date, these models have not been validated with test-retest data. We recruited 11 healthy subjects and conducted two identical scans on each subject on the same day. We considered four different models (one- and two-tissue compartment kinetic models, likelihood estimation in graphical analysis (LEGA; a bias-free alternative to the graphical method), and basis pursuit) along with fast noniterative approximations to the kinetic models. We considered four different outcome measures (total volume of distribution (V(T)), binding potential with (BP) and without (BP(1)), free-fraction adjustment, and specific-to-nonspecific equilibrium partition coefficient (BP(2))). To assess the performance of each model, we compared results using six different metrics (percent difference (PD) and within-subject mean sum of squares for reproducibility, interclass coefficient for reliability, variance across subjects, identifiability based on bootstrap resampling of residuals for each method, and time stability analysis to determine minimal required scanning time). We considered analysis of both at the voxel level and at the region of interest (ROI) level and compared results from these two approaches to assess agreement. We determined that 100 mins of scanning time is adequate and that for ROI-level analysis, LEGA gives best results. Average PD is 5.51 for V(T), 20.7 for BP, 17.2 for BP(1), and 16.5 for BP(2) across all regions. For voxel-level analysis we determined that the one-tissue compartment noniterative model is best.

Metabolite considerations in the in vivo quantification of serotonin transporters using 11C-DASB and PET in humans.

UNLABELLED: PET studies of the serotonin (5-hydroxytryptamine, or 5-HT) transporter are increasingly using (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile (DASB). We noted that the percentage of unmetabolized (11)C-DASB is often lower at 2 min after injection than at 12 min. We hypothesized that this is due to initial "trapping" of the unmetabolized (11)C-DASB compound in the lung, a major 5-HT transporter site and dose-limiting organ. To determine whether binding to an extracranial pool of 5-HT transporters contributes to the lower initial level of unmetabolized (11)C-DASB, we examined the effects of sertraline. METHODS: Eleven healthy volunteers had 2 (11)C-DASB PET scans on the same day, and 6 of the 11 had a third scan after sertraline administration. The unmetabolized (11)C-DASB fraction was measured in arterial plasma as a function of time and was fit with 2 exponentials with no damping, power function damping, or no damping with the first point removed. RESULTS: Power function damping best fit the data as assessed by visual inspection and residuals and resulted in greater distribution volumes than did no damping with the first point removed. Test-retest reproducibility improved when power function damping was used, as compared with no damping with the first point removed. Oral sertraline raised the 2-min unmetabolized (11)C-DASB percentage. CONCLUSION: Measurement and fitting of early metabolism time points improves curve fitting, significantly affects volume-of-distribution determination, and improves test-retest reproducibility. Saturation of lung 5-HT transporters by sertraline prevents the initial trapping of (11)C-DASB. Initial trapping of high-affinity radioligands may be important in the quantification of the binding of other ligands with a high concentration of binding sites in the lungs.