Male Patients With Dilated Cardiomyopathy Exhibiting a Higher Heart Rate Acceleration Capacity or a Lower Deceleration Capacity Are at Higher Risk of Cardiac Death

The effects of dilated cardiomyopathy (DCM) on cardiac autonomic regulation and electrophysiology, and the consequences of such changes, remain unclear. We evaluated the associations between heart rate acceleration capacity (AC) and deceleration capacity (DC), heart structural and functional changes, and cardiac death in 202 healthy controls and 100 DCM patients. The DC was lower and the AC was higher in DCM patients (both males and females). Multivariable, linear, logistic regression analyses revealed that in males, age was positively associated with AC in healthy controls (N = 85); the left atrial diameter (LAD) was positively and the left ventricular ejection fraction (LVEF) was negatively associated with AC in DCM patients (N = 65); age was negatively associated with DC in healthy controls (N = 85); and the LAD was negatively and the LVEF was positively associated with DC in DCM patients (N = 65). In females, only age was associated with either AC or DC in healthy controls (N = 117). Kaplan–Meier analysis revealed that male DCM patients with greater LADs (≥46.5 mm) (long-rank chi-squared value = 11.1, P = 0.001), an elevated AC (≥-4.75 ms) (log-rank chi-squared value = 6.8, P = 0.009), and a lower DC (≤4.72 ms) (log-rank chi-squared value = 9.1, P = 0.003) were at higher risk of cardiac death within 60 months of follow-up. In conclusion, in males, DCM significantly affected both the AC and DC; a higher AC or a lower DC increased the risk of cardiac death

Characterization of the Nucleocytoplasmic Transport Mechanisms of Epstein-Barr Virus BFLF2

Background/Aims: Epstein-Barr virus (EBV) BFLF2, the homologue of herpes simplex virus 1 (HSV-1) UL31, is crucial for the efficient viral DNA packaging and primary egress across the nuclear membrane. However, we still do not know its subcellular transport mechanisms. Methods: Interspecies heterokaryon assays were utilized to detect the nucleocytoplasmic shuttling of BFLF2, and mutation analysis, plasmid transfection and fluorescence microscopy assays were performed to identify the functional nuclear localization sequence (NLS) and nuclear export sequence (NES) of BFLF2 in live cells. Furthermore, the nuclear import and export of BFLF2 were assessed by confocal microscopy, co-immunoprecipitation and immunoblot assays. Results: BFLF2 was confirmed to shuttle between the nucleus and cytoplasm. Two predicted NESs were shown to be nonfunctional, yet we proved that the nuclear export of BFLF2 was mediated through transporter associated with antigen processing (TAP), but not chromosomal region maintenance 1 (CRM1) dependent pathway. Furthermore, one functional NLS, 22RRLMHPHHRNYTASKASAH40, was identified, and the aa22-23, aa22-25, aa28-30 and aa37-40 had an important role in the nuclear localization of BFLF2. Besides, the nuclear import of BFLF2 was demonstrated through Ran-, importin α7-, importin β1- and transportin-1-dependent mechanism that does not require importin α1, α3 and α5. Conclusion: These works are of significance for the further study of the functions of BFLF2 during EBV infection, as well as for further insights into the design of new antiviral drug target and vaccine development against EBV

Characterization of synonymous codon usage bias in pseudorabies virus <i>EP0</i> gene

81-94Codon usage bias among synonymous codons is not an uncommon phenomenon and it is known to involve various biological factors, such as GC compositions, gene length, mutation frequency and patterns, gene expression level, etc. Knowledge on synonymous codon usage may help in understanding the molecular evolution of the individual gene better. In the present study, we examined the codon usage bias between pseudorabies virus (PRV) EP0 gene and the EP0-like genes of 24 reference alpha herpesviruses. Comparative analysis showed noticeable disparities of the synonymous codon usage bias in the 25 alpha herpesviruses, indicated by codon adaptation index, an effective number of codons (ENc) and GC3s value. The codon usage pattern of PRV EP0 gene was phylogenetically conserved and similar to that of the EP0-like genes of the genus Mardivirus of alphaherpesvirus, with a strong bias towards the codons with C and G at the third codon position. Cluster analysis of codon usage pattern of PRV EP0 gene with its reference alpha herpesviruses demonstrated that the codon usage bias of EP0-like genes of 25 alpha herpesviruses had close relation with their gene functions. ENc-plot revealed that the genetic heterogeneity in PRV EP0 gene and the 24 reference alpha herpesviruses was constrained by G+C content, but not gene length. In addition, comparison of codon preferences in the EP0 gene of PRV with those of E. coli, yeast and human revealed that there were 40 codons showing distinct usage differences between PRV and yeast, 27 between PRV and E. coli, but only 22 between PRV and human. Therefore, thehuman expression system may be more suitable for expression of PRV EP0 gene. In conclusion, these results may improve our understanding of the evolution, pathogenesis and functional studies of PRV