A novel mutation in hERG gene associated with azithromycin-induced acquired long QT syndrome.

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.

OsNAC103, an NAC transcription factor negatively regulates plant height in rice.

MAIN CONCLUSION: OsNAC103 negatively regulates rice plant height by influencing the cell cycle and crosstalk of phytohormones. Plant height is an important characteristic of rice farming and is directly related to agricultural yield. Although there has been great progress in research on plant growth regulation, numerous genes remain to be elucidated. NAC transcription factors are widespread in plants and have a vital function in plant growth. Here, we observed that the overexpression of OsNAC103 resulted in a dwarf phenotype, whereas RNA interference (RNAi) plants and osnac103 mutants showed no significant difference. Further investigation revealed that the cell length did not change, indicating that the dwarfing of plants was caused by a decrease in cell number due to cell cycle arrest. The content of the bioactive cytokinin N6-Δ2-isopentenyladenine (iP) decreased as a result of the cytokinin synthesis gene being downregulated and the enhanced degradation of cytokinin oxidase. OsNAC103 overexpression also inhibited cell cycle progression and regulated the activity of the cell cyclin OsCYCP2;1 to arrest the cell cycle. We propose that OsNAC103 may further influence rice development and gibberellin-cytokinin crosstalk by regulating the Oryza sativa homeobox 71 (OSH71). Collectively, these results offer novel perspectives on the role of OsNAC103 in controlling plant architecture.

Influence of nitrogen availability on Cd accumulation and acclimation strategy of Populus leaves under Cd exposure.

Nitrogen (N) plays crucial roles in chlorophyll concentration, photosynthesis, and stress tolerance of plant leaves. This study conducted a greenhouse experiment combined with Cd and N treatments to elucidate the mechanism underlying the influence of N on Cd accumulation and acclimation strategy in Populus leaves. Chlorophyll concentration and net photosynthetic rates (A) in leaves were unaltered by Cd exposure regardless of N condition. Nitrogen availability alter acclimation strategy of poplar leaves under cadmium exposure. Under sufficient N, Cd accumulation in leaves was elevated with increased intensity and duration of Cd exposure; Cd accumulation reached ca. 28 µg g-1 dry weight and 260 µg plant-1 after 60 days of exposure to high level of Cd (20 mg Cd kg-1 soil), and this finding indicates a large potential for Cd phytoextraction. Poplar leaves exhibited high capacity for antioxidant defense and stress tolerance and avoided oxidative damage under high Cd exposure. The levels of phytohormones and antioxidants in leaves and the relative expressions of critical genes encoding antioxidant enzymes were up-regulated under sufficient N condition. Nitrogen deficiency decreased chlorophyll concentration and net photosynthetic rates (A) and interfered with the production of N metabolites, resulting in a low level of phytohormones and antioxidants that are responsible for stress tolerance. The low levels of Cd accumulation in leaves may be a self-protecting strategy to prevent severe oxidative damage due to the decreased capacities for stress tolerance under N deficiency.

The influence of nitrogen availability on anatomical and physiological responses of Populus alba × P. glandulosa to drought stress.

BACKGROUND: Drought and nitrogen (N) deficiency are two major limiting factors for forest productivity in many ecosystems. Elucidating the mechanisms underlying the influence of soil N availability on drought responses of tree species is crucial to improve tree growth under drought. RESULTS: The root proliferation under drought was enhanced by adequate N application. Vessel frequency in xylem increased upon drought, with more significant increase under adequate N conditions compared with that under low N conditions, possibly leading to increased hydraulic safety. Nitrogen application under drought increased indole acetic acid (IAA), which contributed to the adaptive changes of xylem. Nitrogen application increased leaf abscisic acid (ABA) concentration, therefore regulated stomata adjustment, and promoted intrinsic water use efficiency (WUEi). Moreover, N application promoted antioxidant defense in leaves by showing increased level of free proline and carotenoid, which improved drought tolerance and growth performance of poplars. CONCLUSIONS: Anatomical and physiological responses of Populus to drought were suppressed by N deficiency. Adequate N application promoted adaptive changes of root and xylem under drought and increased hydraulic safety. Nitrogen addition under drought also increased leaf ABA level which may regulate stomata adjustment and promote WUEi. Moreover, nitrogen application improved antioxidant defense in leaves with increased levels of antioxidants. These positive regulations improved drought tolerance and growth performance of poplars.