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The human ether-a-go-go-related gene (hERG) K + channel conducts a rapidly activating delayed rectifier K + current (I Kr ), which is essential for normal electrical activity of the heart. Precise regulation of hERG channel biogenesis is critical for serving its physiological functions, and deviations from the regulation result in human diseases. However, the mechanism underlying the precise regulation of hERG channel biogenesis remains elusive. Here, by using forward genetic screen, we found that PATR-1, the Caenorhabditis elegans homolog of the yeast DNA topoisomerase 2-associated protein PAT1, is a critical regulator for the biogenesis of UNC-103, the ERG K + channel in C. elegans . A loss-of-function mutation in patr-1 down-regulates the expression level of UNC-103 proteins and suppresses the phenotypic defects resulted from a gain-of-function mutation in the unc-103 gene. Furthermore, downregulation of PATL1 and PATL2, the human homologs of PAT1, decreases protein levels and the current density of native hERG channels in SH-SY5Y cells and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Knockdown of PATL1 and PATL2 elongates the duration of action potentials in hiPSC-CMs, suggesting that PATL1 and PATL2 affect the function of hERG channels and hence electrophysiological characteristics in the human heart. Further studies found that PATL1 and PATL2 interact with TFIIE, a general transcription factor required for forming the RNA polymerase II preinitiation complex, and dual-luciferase reporter assays indicated that PATL1 and PATL2 facilitate the transcription of hERG mRNAs. Together, our study discovers that evolutionarily conserved DNA topoisomerase 2-associated proteins regulate the biogenesis of hERG channels via a transcriptional mechanism.

Objective: To systematically review the effect of sustained lung inflation (SLI) in preterm infants with a gestational age of <34 weeks., Methods: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, Chinese Journal Full-text Database, and Weipu Database were searched for randomized controlled trials (RCTs) on the application of SLI versus noninvasive positive pressure ventilation alone in preterm infants. Revman 5.3 was used to perform a Meta analysis for the RCTs which met the inclusion criteria., Results: A total of 9 RCTs were included, with 1 432 preterm infants in total (with a gestational age of 23-33.7 weeks). The Meta analysis showed that compared with the control group, the SLI group had a significantly lower proportion of the infants who needed mechanical ventilation within 72 hours (51.9% vs 56.9%, RR=0.91, P=0.04, 95%CI: 0.83-0.99). There were no significant differences between the two groups in the mortality rate, rate of use of pulmonary surfactant, and incidence rates of related complications (bronchopulmonary dysplasia, pneumothorax, and grade III-IV intracranial hemorrhage) (P>0.05)., Conclusions: SLI can reduce the use of mechanical ventilation in preterm infants with a gestational age of <34 weeks and does not increase the risk of other complications.

Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K + channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K + channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4.2) K + channel subunits through a heat shock protein (HSP) 70-independent mechanism, whereas a mutated DNAJB12 that did not undergo oligomerization itself failed to assemble ERG channel subunits into tetramers in vitro and in C. elegans. Overexpressing DNAJB14 significantly rescued the defective function of human ether-a-go-go-related gene (hERG) mutant channels associated with long QT syndrome (LQTS), a condition that predisposes to life-threatening arrhythmia, by stabilizing the mutated proteins. Thus, chaperone proteins are required for subunit stability and assembly of K + channels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The WRKY family is one of the most important transcription factor families in plants, involved in the regulation of a broad range of biological roles. The recent releases of whole-genome sequences of pepper (Capsicum annuum L.) allow us to perform a genome-wide identification and characterization of the WRKY family. In this study, 61 CaWRKY proteins were identified in the pepper genome. Based on protein structural and phylogenetic analyses, these proteins were classified into four main groups (I, II, III, and NG), and Group II was further divided into five subgroups (IIa to IIe). Chromosome mapping analysis indicated that CaWRKY genes are distributed across all 12 chromosomes, although the location of four CaWRKYs (CaWRKY58-CaWRKY61) could not be identified. Two pairs of CaWRKYs located on chromosome 01 appear to be tandem duplications. Furthermore, the phylogenetic tree showed a close evolutionary relationship of WRKYs in three species from Solanaceae. In conclusion, this comprehensive analysis of CaWRKYs will provide rich resources for further functional studies in pepper.

Tomato yellow leaf curl virus is one of the main diseases affecting tomato production worldwide. Previous studies have shown that Ty-2 is an important resistance gene located between molecular markers C2&#95;At2g28250 (82.3 cM) and T0302 (89.0 cM), and exhibits strong resistance to tomato yellow leaf curl virus in Asia. In this study, Ty-2 candidate genes were subjected to bioinformatic analysis for the sequenced tomato genome. We identified 69 genes between molecular markers C2&#95;At2g28250 and T0302, 22 of which were disease-related resistant genes, including nucleotide binding site-leucine-rich repeat disease resistance genes, protease genes (protein kinase, kinase receptor, and protein isomerase), cytochromes, and transcription factors. Expressed sequence tag analysis revealed that 77.3% (17/22) of candidate disease-resistance genes were expressed, involving 143 expressed sequence tags. Based on full-length cDNA sequence analysis, 7 candidate genes were found, 4 of which were involved in tomato responses to pathogens. Microarray expression analysis also showed that most candidate genes were involved in the tomato responses to multiple pathogens, including fungi, viruses, and bacteria. RNA-seq expression analysis revealed that all candidate genes participated in tomato growth and development.

Voltage-gated Kv4 channels control the excitability of neurons and cardiac myocytes by conducting rapidly activating-inactivating currents. The function of Kv4 channels is profoundly modulated by K(+) channel interacting protein (KChIP) soluble auxiliary subunits. However, the in vivo mechanism of the modulation is not fully understood. Here, we identified three C. elegans KChIP-like (ceKChIP) proteins, NCS-4, NCS-5, and NCS-7. All three ceKChIPs alter electrical characteristics of SHL-1, a C. elegans Kv4 channel ortholog, currents by slowing down inactivation kinetics and shifting voltage dependence of activation to more hyperpolarizing potentials. Native SHL-1 current is completely abolished in cultured myocytes of Triple KO worms in which all three ceKChIP genes are deleted. Reexpression of NCS-4 partially restored expression of functional SHL-1 channels, whereas NCS-4(efm), a NCS-4 mutant with impaired Ca(2+)-binding ability, only enhanced expression of SHL-1 proteins, but failed to transport them from the Golgi apparatus to the cell membrane in body wall muscles of Triple KO worms. Moreover, translational reporter revealed that NCS-4 assembles with SHL-1 K(+) channels in male diagonal muscles. Deletion of either ncs-4 or shl-1 significantly impairs male turning, a behavior controlled by diagonal muscles during mating. The phenotype of the ncs-4 null mutant could be rescued by reexpression of NCS-4, but not NCS-4(efm), further emphasizing the importance of Ca(2+) binding to ceKChIPs in regulating native SHL-1 channel function. Together, these data reveal an evolutionarily conserved mechanism underlying the regulation of Kv4 channels by KChIPs and unravel critical roles of ceKChIPs in regulating muscle cell excitability and animal behavior in C. elegans., (Copyright © 2015 the authors 0270-6474/15/351880-12$15.00/0.)

The objective of the present study was to analyze the genetic diversity of tomato yellow leaf curl virus (TYLCV). Representative TYLCV sequences were searched in the National Center for Biotechnology Information database. Comprehensive analysis of TYLCV was performed using bioinformatics by examining gene structure, sequence alignments, phylogeny, GC content, and homology. Forty-eight representative TYLCV sequences were selected from 48 regions in 29 countries. The results showed that all TYLCV sequences were 2752-2794 nucleotides in length, which encoded 6 open reading frames (AV1, AV2, AC1, AC2, AC3, and AC4). GC content ranged from 0.41-0.42. Sequence alignment showed a number of insertions and deletions within these TYLCV sequences. Phylogenetic tree results revealed that the sequences were divided into 10 classes; homology of the sequences ranged from 72.8 to 98.6%. All 48 sequences contained the typical structure of TYLCV, including open reading frames and intergenic regions. These results provide a theoretical basis for the identification and evolution of the virus in the future.

High-field electron spin resonance measurements of an antiferromagnet Ca3ZnMnO6 isostructure, with the Ising-chain multiferroic Ca3CoMnO6, have been carried out. Two distinct resonance modes were observed below TN = 25 K, which is well explained by conventional antiferromagnetic resonance theory with easy-plane anisotropy. The zero-field spin gap is derived to be about 166 GHz, originating from the easy-plane anisotropy and exchange interaction. Our result suggests that the Dzyaloshinsky-Moriya interaction, which may induce spin canting, is absent. Disappearance of Ising anisotropy in Ca3ZnMnO6 suggests that the Co(4+) ion, as well as the Co-Mn superexchange, plays an important role for the Ising nature in Ca3CoMnO6.

It is a practical strategy to screen for mutants in the research of plant functional genomics. Comparing with classical T-DNA knock-out mutagenesis technology by the loss-of-function mutation, the activation T-DNA tagging technique based on the gain-of-function mutation has its own particular advantages, mainly characterized by producing dominant mutants of genes with functional redundancy and easily cloning of the genes. First, the basic principle of activation tagging, and the progress of its application in the research on plant functional genomics was reviewed, especially in Arabidopsis and rice. The recent research progress in the mechanism of plant biotic and abiotic stress tolerance and of plant development unraveled by the method of activation tagging was then addressed. Finally, the limitation and prospects of this technique were discussed.