Genetic and Epigenetic Control of Soybean Agronomic Traits

Greater soybean productivity depends on the genetic improvement of yield components, epigenetic effects and the interactions with surrounding environment. We explored the possibility of soybean improvement by conventional biparental crossing of soybean lines, differing by seed quality, yield, and resistance to a range of pathogens, including soybean cyst nematode (SCN). We investigated the role of Resistance to Heterodera glycines (Rhg) 1 and 4 loci in soybean resistance to SCN, race 2 and 3. Further, we evaluated the adaptability of temperate-origin soybean lines in tropical environments of Rwanda. Lastly, we examined gene expression, RNA splicing, DNA methylation and their interactions in three distinct developmental stages of soybean nodules. Briefly, compared to the parental lines, the recombinant inbred lines (RILs) generated from the biparental cross, represented varying phenotypes for seed yield, protein and oil contents, with high broad-sense heritability scores. This suggests a possibility of selection of best individuals with potentially high genetic gain for each trait. Analysis of gene expression, nucleotide sequences, and copy number variation of Rhg1 and Rhg4 in a set of RILs revealed that resistance to race 2 is mediated independently of Rhg1 and Rhg4. Importantly, a QTL on chromosome 17, associated with resistance to SCN race 2 was identified, a finding that provides the foundation for cloning the underlying SCN resistance gene. Our data suggested a possibility to stack favorable SCN resistance alleles in high yielding cultivars as the yield of RILs harboring SCN resistance alleles to race 2, compared to the susceptible RILs, was not negatively impacted. Some US-developed soybean lines could adapt and double the current local yield potential. However, our data revealed a significant GXE interaction, implying their fitness in specific micro-climates of Rwanda. Amino acid profile and consequently seed storage protein can be improved through the manipulation of soybean nodulation. Our results revealed dynamic changes in gene expression, alternative splicing events and extensive DNA methylation reprogramming in the developing nodules. The results also revealed novel insights to the associations between the transcriptome, spliceome, and methylome of the developing soybean nodules and improved our understanding of the genetic and epigenetic mechanisms controlling soybean nodulation

Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

IntroductionPemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.MethodsThe phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.ResultsMaximum tolerated dose was gemcitabine 1500 mg/m2, followed by pemetrexed 500 mg/m2. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).ConclusionsTwice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients