Germination is a unique developmental transition from metabolically quiescent seed to actively growing seedling that requires an ensemble of hydrolases for coordinated nutrient mobilization to support heterotrophic growth until autotrophic photosynthesis is established. This study reveals two crucial transcription factors, MYBS1 and MYBGA, present in rice (Oryza sativa) and barley (Hordeum vulgare), that function to integrate diverse nutrient starvation and gibberellin (GA) signaling pathways during germination of cereal grains. Sugar represses but sugar starvation induces MYBS1 synthesis and its nuclear translocation. GA antagonizes sugar repression by enhancing conuclear transport of the GA-inducible MYBGA with MYBS1 and the formation of a stable bipartite MYB-DNA complex to activate the a-amylase gene. We further discovered that not only sugar but also nitrogen and phosphate starvation signals converge and interconnect with GA to promote the conuclear import of MYBS1 and MYBGA, resulting in the expression of a large set of GA-inducible but functionally distinct hydrolases, transporters, and regulators associated with mobilization of the full complement of nutrients to support active seedling growth in cereals.

IntroductionPrevious studies have shown an association between gout and/or hyperuricemia and a subsequent increase in cardiovascular disease (CVD) outcomes. Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state, improves endothelial function, and prevents atherosclerosis progression. Accordingly, we tested the hypothesis that a positive association between allopurinol therapy in gout patients and future cardiovascular outcomes is present using a population-based matched-cohort study design.MethodsPatients aged ≥40 years with newly diagnosed gout having no pre-existing severe form of CVD were separated into allopurinol (n = 2483) and non-allopurinol (n = 2483) groups after matching for age, gender, index date, diabetes mellitus, hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis, and Charlson comorbidity index.ResultsWith a median follow-up time of 5.25 years, the allopurinol group had a modest increase in cardiovascular risk [relative risk, 1.20; 95% confidence interval (CI), 1.08–1.34]. A Cox proportional hazard model adjusted for chronic kidney disease, uremia, and gastric ulcer gave a hazard ratio (HR) for cardiovascular outcomes of 1.25 (95% CI, 1.10–1.41) in gout patients receiving allopurinol compared with the non-allopurinol group. In further analysis of patients receiving urate-lowering therapy, the uricosuric agent group (n = 1713) had an adjusted HR of 0.83 (0.73–0.95) for cardiovascular events compared with the allopurinol group.ConclusionsThe current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort study, thus could potentially bias the effect estimate.

In plants, source-sink communication plays a pivotal role in crop productivity, yet the underlying regulatory mechanisms are largely unknown. The SnRK1A protein kinase and transcription factor MYBS1 regulate the sugar starvation signaling pathway during seedling growth in cereals. Here, we identified plant-specific SnRK1A-interacting negative regulators (SKINs). SKINs antagonize the function of SnRK1A, and the highly conserved GKSKSF domain is essential for SKINs to function as repressors. Overexpression of SKINs inhibits the expression of MYBS1 and hydrolases essential for mobilization of nutrient reserves in the endosperm, leading to inhibition of seedling growth. The expression of SKINs is highly inducible by drought and moderately by various stresses, which is likely related to the abscisic acid (ABA)-mediated repression of SnRK1A under stress. Overexpression of SKINs enhances ABA sensitivity for inhibition of seedling growth. ABA promotes the interaction between SnRK1A and SKINs and shifts the localization of SKINs from the nucleus to the cytoplasm, where it binds SnRK1A and prevents SnRK1A and MYBS1 from entering the nucleus. Our findings demonstrate that SnRK1A plays a key role regulating source-sink communication during seedling growth. Under abiotic stress, SKINs antagonize the function of SnRK1A, which is likely a key factor restricting seedling vigor

BackgroundRecent studies have shown that inhaled corticosteroids (ICS) can exert anti-inflammatory effects for chronic airway diseases, and several observational studies suggest that they play a role as cancer chemopreventive agents, particularly against lung cancer. We aimed to examine whether regular ICS use was associated with a reduced risk for future malignancy in patients with newly diagnosed adult-onset asthma.MethodsWe used a population-based cohort study between 2001 and 2008 with appropriate person-time analysis. Participants were followed up until the first incident of cancer, death, or to the end of 2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer development. Kaplan–Meier cancer-free survival curves of two groups were compared.ResultsThe exposed group of 2,117 regular ICS users and the nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5 years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation 2.4) person-years of follow-up for the ICS users and the comparator group of non-ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated at 1.33 with 95% confidence interval (CI), 1.00–1.76, P=0.0501. The Kaplan–Meier curves for overall cancer-free proportions of both groups were not significant (log-rank, P=0.065). Synergistic interaction of concurrent presence of regular ICS use was conducted using “ICS-negative and chronic obstructive pulmonary disease (COPD)-negative” as the reference. The aHR for the group of “ICS-positive, COPD-negative” did not reach statistically significant levels with aHR at 1.38 (95% CI, 0.53–3.56). There was a statistically significant synergistic interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78 (95% CI, 2.10–6.81).ConclusionThe protective effect of regular ICS use in the studied East Asian patients with adult-onset asthma was not detectable, contrary to reports of previous studies that ICS might prevent the occurrence of future cancer.