The high molecular weight glutenin subunit (HMW-GS) composition of a collection of 107 Argentinean bread wheat cultivars was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Allelic variation at the Glu-1 loci was identified and its frequency calculated. Eleven alleles were detected, three encoded at the Glu-A1 locus, six at the Glu-B1 locus and two at the Glu-D1 locus. A low frequency of the null allele at the Glu-A1 locus and a high frequency of subunits 5+10 at the Glu-D1 locus were observed. Reversed phase-high performance liquid chromatography (RP-HPLC) analysis was used to further characterise HMW-GS. Two different types of Bx subunit 8 (named subunits 8 and 8*) were detected, the latter having shorter elution time. Subunit 8* was not identifiable by SDS-PAGE. According to quantification by RP-HPLC analysis, two groups of subunit 7 were observed. One group, with a relatively high proportion of subunit 7 (approximately 39% of the total amount of HMW-GS) appeared in cultivars with allele 7+8* at the Glu-B1 locus; a second group of subunit 7 (around 24% of the total amount of HMW-GS), was found in alleles 7+8, 7+8* and 7+9. Restriction fragment length polymorphisms (RFLP) analyses of HMW-GS genes were also carried out after digestion of genomic DNA with HindIII and TaqI restriction enzymes. The relationship between DNA fragment size and glutenin subunits, as estimated by electrophoretic mobility in SDS-PAGE, was also examined. The restriction enzyme TaqI demonstrated to be a useful tool to detect homozygous plants in selection programs against the Glu-A1 null allele.

The effects of Triticum monococcum glutenin loci on cookie making quality and predictive tests for bread making quality were evaluated in recombinant substitution lines (RSLs) between chromosome 1Am from T. monococcum and chromosome 1A from Chinese Spring. All four combinations of high molecular weight (HMr-GS) and low molecular weight glutenin alleles (LMr-GS) were studied in a factorial design to evaluate their interactions. Grain protein content was used as a covariable to evaluate the effect of these loci independently of the variation in protein content among lines. No significant interactions were detected indicating an additive effect. RSLs carrying the HMr-GS from T. monococcum showed a 13.6% increase in SDS sedimentation volume (p=0.004) and a significant reduction in cookie diameter (-5.2%, p=0.02), and cookie quality (-6.8%, p=0.02). RSLs carrying the LMr-GS from T. monococcum showed a significant decrease in the proportion of polymeric protein (-2.8%, p<0.0001), SDS sedimentation volume (-8.1%, p=0.03) and gluten strength (-16.5%, p=0.01), and a significant increase in cookie quality (5.9%, p=0.05). The T. monococcum LMr-GS allele has potential value to be used in soft wheat breeding programs. These results suggest that diploid T. monococcum could be a valuable source for new allelic variation for storage proteins loci and new quality characteristics. © 2002 Elsevier Science Ltd.

Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was >20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was >20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to > 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus.