BackgroundSoybean seed weight is not only a yield component, but also a critical trait for various soybean food products such as sprouts, edamame, soy nuts, natto and miso. Linkage analysis and genome-wide association study (GWAS) are two complementary and powerful tools to connect phenotypic differences to the underlying contributing loci. Linkage analysis is based on progeny derived from two parents, given sufficient sample size and biological replication, it usually has high statistical power to map alleles with relatively small effect on phenotype, however, linkage analysis of the bi-parental population can’t detect quantitative trait loci (QTL) that are fixed in the two parents. Because of the small seed weight difference between the two parents in most families of previous studies, these populations are not suitable to detect QTL that have considerable effects on seed weight. GWAS is based on unrelated individuals to detect alleles associated with the trait under investigation. The ability of GWAS to capture major seed weight QTL depends on the frequency of the accessions with small and large seed weight in the population being investigated. Our objective was to identify QTL that had a pronounced effect on seed weight using a selective population of soybean germplasm accessions and the approach of GWAS and fixation index analysis.ResultsWe selected 166 accessions from the USDA Soybean Germplasm Collection with either large or small seed weight and could typically grow in the same location. The accessions were evaluated for seed weight in the field for two years and genotyped with the SoySNP50K BeadChip containing >42,000 SNPs. Of the 17 SNPs on six chromosomes that were significantly associated with seed weight in two years based on a GWAS of the selective population, eight on chromosome 4 or chromosome 17 had significant Fst values between the large and small seed weight sub-populations. The seed weight difference of the two alleles of these eight significant SNPs varied from 8.1 g to 11.7 g/100 seeds in two years. We also identified haplotypes in three haplotype blocks with significant effects on seed weight. These findings were validated in a panel with 3753 accessions from the USDA Soybean Germplasm Collection.ConclusionThis study highlighted the usefulness of selective genotyping populations coupled with GWAS and fixation index analysis for the identification of QTL with substantial effects on seed weight in soybean. This approach may help geneticists and breeders to more efficiently identify major QTL controlling other traits. The major regions and haplotypes we have identified that control seed weight differences in soybean will facilitate the identification of genes regulating this important trait.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3922-0) contains supplementary material, which is available to authorized users.

Vitamin A (VA) deficiency is the leading cause of blindness in children in developing countries. Dietary intervention with foods rich in provitamin A carotenoids, such as beta-carotene (betaC), has been suggested as one solution to this problem. The objective of the two studies described in this paper was to examine the utilization of betaC as a source of VA at different stages of VA depletion using the Mongolian gerbil as a model. Male 4- to 5-wk-old Mongolian gerbils were fed powdered betaC-free semipurified diets either with or without VA for 26 d (Study 1), or without VA for 8-10 wk (Study 2). Gerbils were then fed diets with or without VA (20.9 nmol/g diet) and/or betaC [(67.0 micromol/g diet (Study 1) and 145.9 micromol/g diet (Study 2)] for variable periods. Two (Study 1) or three (Study 2) days before termination of the study, 3-4 gerbils per group were dosed orally with 14C-betaC. Tissues were evaluated for VA and betaC content by HPLC. Liver was extracted with and without saponification to evaluate 14C-betaC and 14C-VA content. The results demonstrate the following: 1) the gerbil is an appropriate animal model to study betaC utilization; 2) 20.9 nmol VA/g diet is more than sufficient for this species; 3) the daily VA utilization rate for this species is calculated to be 3.1 microg/100 g body weight; 4) a highly bioavailable source of betaC at a 6:1 weight ratio of betaC:VA is sufficient to reverse marginal VA status in this model; and 5) a highly bioavailable source of betaC fed between a 6:1 and 13:1 weight ratio to VA provides equivalent VA status as preformed VA in Mongolian gerbils.

Tyrosine kinase domains dynamically fluctuate between two main structural forms that are referred to as type I (DFG-in) or type II (DFG-out) conformations. Comprehensive data comparing type I and type II inhibitors are currently lacking for NTRK fusion-driven cancers. Here we used a type II NTRK inhibitor, altiratinib, as a model compound to investigate its inhibitory potential for larotrectinib (type I inhibitor)-resistant mutations in NTRK. Our study shows that a subset of larotrectinib-resistant NTRK1 mutations (V573M, F589L and G667C) retains sensitivity to altiratinib, while the NTRK1V573M and xDFG motif NTRK1G667C mutations are highly sensitive to type II inhibitors, including altiratinib, cabozantinib and foretinib. Moreover, molecular modeling suggests that the introduction of a sulfur moiety in the binding pocket, via methionine or cysteine substitutions, specifically renders the mutant kinase hypersensitive to type II inhibitors. Future precision treatment strategies may benefit from selective targeting of these kinase mutants based on our findings.