Recent advances in understanding the role of two mitogen-activated protein kinase cascades in plant immunity.

The mitogen-activated protein kinase (MAPK/MPK) cascade is an important intercellular signaling module that regulates plant growth, development, reproduction, and responses to biotic and abiotic stresses. A MAPK cascade usually consists of a MAPK kinase kinase (MAPKKK/MEKK), a MAPK kinase (MAPKK/MKK/MEK), and a MAPK. The well-characterized MAPK cascades in plant immunity to date are the MEKK1-MKK1/2-MPK4 cascade and the MAPKKK3/4/5-MKK4/5-MPK3/6 cascade. Recently, major breakthroughs have been made in understanding the molecular mechanisms associated with the regulation of immune signaling by both of these MAPK cascades. In this review, we highlight the most recent advances in understanding the role of both MAPK cascades in activating plant defense and in suppressing or fine-tuning immune signaling. We also discuss the molecular mechanisms by which plants stabilize and maintain the activation of MAPK cascades during immune signaling. Based on this review, we reveal the complexity and importance of the MEKK1-MKK1/2-MPK4 cascade and the MAPKKK3/4/5-MKK4/5-MPK3/6 cascade, which are tightly controlled by their interacting partners or substrates, in plant immunity.

Exploring the impact of electrocardiographic parameters on the risk of common arrhythmias: a two-sample Mendelian randomization study.

Background: Observational studies have shown that heart rate (HR), heart rate variability (HRV), P-wave terminal force, P-wave duration, T-wave amplitude and PR interval are associated with risk factors for atrial fibrillation (AF) or bradycardia. Arrhythmias are associated with many causes of hospitalization. However, observational studies are susceptible to confounding factors that have not yet been identified. The objective of this study was to clarify the causal relationships by Mendelian randomization analysis. Methods: We conducted a two-sample and multivariate Mendelian randomization (MVMR) analysis using genome-wide association study (GWAS) data from a European population to assess the total and direct causal effects of HR, three HRV traits, P-wave terminal force, P-wave duration, T-wave top amplitude in five-lead modes, and the PR interval on the risk of AF (N=191,205), bradycardia (N=463,010), and supraventricular tachycardia (SVT) (N=463,010). Results: The results of the univariate MR analysis revealed the following significant causal effects: the higher the genetically predicted PR interval, the lower the risk of AF; the higher the HR and T-wave top amplitude (aVR leads and V3 + V4 + aVL leads), the lower the risk of bradycardia; and the higher HR and the lower PR interval, the higher the risk of SVT. The multivariate MR results indicated that the HRV_standard deviation of the normal-to-normal (SDNN) interval had an independent causal effect on the risk of AF [odds ratio (OR): 0.515; 95% confidence interval (CI): 0.278-0.954; P=0.03], and the T-wave top amplitude in the aVR leads (OR: 0.998; 95% CI: 0.996-0.999; P<0.001) and the HRV_SDNN (OR: 0.988; 95% CI: 0.976-1.000; P=0.045) had independent causal effects on the risk of bradycardia. Conclusions: The HRV_SDNN had an independent causal effect on AF, while the HRV_SDNN and T-wave top amplitude in the aVR leads had independent causal effects on bradycardia, which suggests that some of the electrocardiographic parameters have preventive effects on the incidence of AF and bradycardia.