Recognition of high-specificity hERG K+ channel inhibitor-induced arrhythmia in cardiomyocytes by automated template matching.

Cardiovascular disease (CVD) is the number one cause of death in humans. Arrhythmia induced by gene mutations, heart disease, or hERG K+ channel inhibitors is a serious CVD that can lead to sudden death or heart failure. Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals. However, parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats, and it is difficult to achieve automated and efficient arrhythmic recognition with these methods. In this work, we developed a unique automated template matching (ATM) cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system. The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation. The performance of the ATM model under long-term astemizole, droperidol, and sertindole treatment at different doses was determined. The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy (100% for astemizole treatment and 99.14% for droperidol and sertindole treatment) than the ATM model based on arrhythmic multitemplates. We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.

Transcriptomic and metabolomic analyses reveal mechanisms of adaptation to salinity in which carbon and nitrogen metabolism is altered in sugar beet roots.

BACKGROUND: Beta vulgaris L. is one of the main sugar-producing crop species and is highly adaptable to saline soil. This study explored the alterations to the carbon and nitrogen metabolism mechanisms enabling the roots of sugar beet seedlings to adapt to salinity. RESULTS: The ionome, metabolome, and transcriptome of the roots of sugar beet seedlings were evaluated after 1 day (short term) and 7 days (long term) of 300 mM Na+ treatment. Salt stress caused reactive oxygen species (ROS) damage and ion toxicity in the roots. Interestingly, under salt stress, the increase in the Na+/K+ ratio compared to the control ratio on day 7 was lower than that on day 1 in the roots. The transcriptomic results showed that a large number of differentially expressed genes (DEGs) were enriched in various metabolic pathways. A total of 1279 and 903 DEGs were identified on days 1 and 7, respectively, and were mapped mainly to 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of the genes were involved in carbon metabolism and amino acid (AA) biosynthesis. Furthermore, metabolomic analysis revealed that sucrose metabolism and the activity of the tricarboxylic acid (TCA) cycle increased in response to salt stress. After 1 day of stress, the content of sucrose decreased, whereas the content of organic acids (OAs) such as L-malic acid and 2-oxoglutaric acid increased. After 7 days of salt stress, nitrogen-containing metabolites such as AAs, betaine, melatonin, and (S)-2-aminobutyric acid increased significantly. In addition, multiomic analysis revealed that the expression of the gene encoding xanthine dehydrogenase (XDH) was upregulated and that the expression of the gene encoding allantoinase (ALN) was significantly downregulated, resulting in a large accumulation of allantoin. Correlation analysis revealed that most genes were significantly related to only allantoin and xanthosine. CONCLUSIONS: Our study demonstrated that carbon and nitrogen metabolism was altered in the roots of sugar beet plants under salt stress. Nitrogen metabolism plays a major role in the late stages of salt stress. Allantoin, which is involved in the purine metabolic pathway, may be a key regulator of sugar beet salt tolerance.

Transcriptome analysis of sugar beet (Beta vulgaris L.) in response to alkaline stress.

KEY MESSAGE: RNA-seq was used to analyze the transcriptional changes in sugar beet (Beta vulgaris L.) triggered by alkaline solution to elucidate the molecular mechanism underlying alkaline tolerance in sugar beet. Several differentially expressed genes related to stress tolerance were identified. Our results provide a valuable resource for the breeding of new germplasms with high alkaline tolerance. Alkalinity is a highly stressful environmental factor that limits plant growth and production. Sugar beet own the ability to acclimate to various abiotic stresses, especially salt and alkaline stress. Although substantial previous studies on response of sugar beet to saline stress has been conducted, the expressions of alkali-responsive genes in sugar beet have not been comprehensively investigated. In this study, we conducted transcriptome analysis of leaves in sugar beet seedlings treated with alkaline solutions for 0 day (control, C), 3 days (short-term alkaline treatment, ST) and 7 days (long-term alkaline treatment, LT). The clean reads were obtained and assembled into 25,507 unigenes. Among them, 975 and 383 differentially expressed genes (DEGs) were identified in the comparison groups ST_vs_C and LT_vs_C, respectively. Gene ontology (GO) analysis revealed that oxidation-reduction process and lipid metabolic process were the most enriched GO term among the DEGs in ST_vs_C and LT_vs_C, respectively. According to Kyoto Encyclopedia of Genes and Genomes pathway, carbon fixation in photosynthetic organisms pathway were significantly enriched under alkaline stress. Besides, expression level of genes encoding D-3-phosphoglycerate dehydrogenase 1, glutamyl-tRNA reductase 1, fatty acid hydroperoxide lyase, ethylene-insensitive protein 2, metal tolerance protein 11 and magnesium-chelatase subunit ChlI, etc., were significantly altered under alkaline stress. Additionally, among the DEGs, 136 were non-annotated genes and 24 occurred with differential alternative splicing. Our results provide a valuable resource on alkali-responsive genes and should benefit the improvement of alkaline stress tolerance in sugar beet.