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561.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the causes of sudden cardiac death in young people and results from RYR2 mutations in ~60% of CPVT patients. The inheritance of the RYR2 mutations follows an autosomal dominant trait, however, de novo mutations are often identified during familial analysis. In 36 symptomatic CPVT probands with RYR2 mutations, we genotyped their parents and confirmed the origin of the respective mutation. In 26 sets of proband and both parents (trio), we identified 17 de novo mutations (65.4%), seven from their mothers and only two mutations were inherited from their fathers. Among nine sets of proband and mother, five mutations were inherited from mothers. Four other mutations were of unknown origin. The inheritance of RYR2 mutations was significantly more frequent from mothers (n = 12, 34.3%) than fathers (n = 2, 5.7%) (P = 0.013). The mean ages of onset were not significantly different in probands between de novo mutations and those from mothers. Thus, half of the RYR2 mutations in our cohort were de novo, and most of the remaining mutations were inherited from mothers. These data would be useful for family analysis and risk stratification of the disease. 相似文献
562.
563.
Masaki Fukuyo Toshiaki Nakano Yingbiao Zhang Yoshikazu Furuta Ken Ishikawa Miki Watanabe-Matsui Hirokazu Yano Takeshi Hamakawa Hiroshi Ide Ichizo Kobayashi 《Nucleic acids research》2015,43(5):2841-2852
The restriction-modification systems use epigenetic modification to distinguish between self and nonself DNA. A modification enzyme transfers a methyl group to a base in a specific DNA sequence while its cognate restriction enzyme introduces breaks in DNA lacking this methyl group. So far, all the restriction enzymes hydrolyze phosphodiester bonds linking the monomer units of DNA. We recently reported that a restriction enzyme (R.PabI) of the PabI superfamily with half-pipe fold has DNA glycosylase activity that excises an adenine base in the recognition sequence (5′-GTAC). We now found a second activity in this enzyme: at the resulting apurinic/apyrimidinic (AP) (abasic) site (5′-GT#C, # = AP), its AP lyase activity generates an atypical strand break. Although the lyase activity is weak and lacks sequence specificity, its covalent DNA–R.PabI reaction intermediates can be trapped by NaBH4 reduction. The base excision is not coupled with the strand breakage and yet causes restriction because the restriction enzyme action can impair transformation ability of unmethylated DNA even in the absence of strand breaks in vitro. The base excision of R.PabI is inhibited by methylation of the target adenine base. These findings expand our understanding of genetic and epigenetic processes linking those in prokaryotes and eukaryotes. 相似文献
564.
565.
Gingival epithelial cells function as an innate host defence system to prevent intrusion by periodontal bacteria. Nevertheless, Porphyromonas gingivalis, the most well‐known periodontal pathogen, can enter gingival epithelial cells and pass through the epithelial barrier into deeper tissues. However, it is poorly understood how this pathogen exits from infected cells for further transcellular spreading. The present study was performed to elucidate the cellular machinery exploited by P. gingivalis to exit from immortalized human gingival epithelial cells. P. gingivalis was shown to be internalized with early endosomes positive for the FYVE domain of EEA1 and transferrin receptor, and about half of the intracellular bacteria were then sorted to lytic compartments, including autolysosomes and late endosomes/lysosomes, while a considerable number of the remaining organisms were sorted to Rab11‐ and RalA‐positive recycling endosomes. Inhibition experiments revealed that bacterial exit was dependent on actin polymerization, lipid rafts and microtubule assembly. Dominant negative forms and RNAi knockdown of Rab11, RalA and exocyst complex subunits (Sec5, Sec6 and Exo84) significantly disturbed the exit of P. gingivalis. These results strongly suggest that the recycling pathway is exploited by intracellular P. gingivalis to exit from infected cells to neighbouring cells as a mechanism of cell‐to‐cell spreading. 相似文献
566.
Soichiro Ogaki Seiko Harada Nobuaki Shiraki Kazuhiko Kume Shoen Kume 《BMC developmental biology》2011,11(1):13
Background
We developed an efficient in vitro method to differentiate mouse ES cells into the definitive endoderm (DE) and then Pdx1-expressing pancreatic lineages using mesodermal-derived supporting cells, M15. Using this method, resulting ES cell-derived DE and Pdx1-expressing cells were isolated by cell sorting, and their gene expression profiles were investigated with DNA microarray. Genes that were specifically expressed in DE and/or in Pdx1-expressing cells were extracted and their expression patterns in normal embryonic development were studied. 相似文献567.
Interactions between GNRA tetraloops and their receptors are found frequently as modular units in various types of naturally occurring structured RNAs. Due to their functional importance, GNRA/receptor interactions have been studied extensively with regard to their 3D structures and biochemical and biophysical properties. Artificial non-natural GNRA/receptor modules have also been generated not only to obtain a better understanding of this class of motifs in natural RNA structures but also for application of these modular units to the design and construction of artificial RNA structures that can be used as platforms to generate functional RNAs applicable for nanobiotechnology. In this review, we present a survey of structures, functions, and analyses as well as artificial generation and application of GNRA/receptor interacting modules. 相似文献
568.
Takahashi S Nakajima Y Imaizumi T Furuta Y Ohshiro Y Abe K Yamada RH Kera Y 《Applied microbiology and biotechnology》2011,89(4):1213-1221
The yeast Cryptococcus humicola has several attractive properties for practical applications such as in bioremediation and as a source of industrially useful
enzymes and compounds. We have developed an autonomously replicating vector of C. humicola to improve its properties. We initially tried to isolate an autonomously replicating sequence (ARS) from genomic DNA by transformation
using a genomic DNA library. We obtained a candidate plasmid vector harboring an ARS that gave high transformation efficiency.
Southern blot analysis of transformants revealed the autonomous replication of the introduced vector in some transformants.
However, the vector was not only variously altered in length but also linearized. PCR analysis indicated that a telomere-like
sequence repeat (TTAGGGGG)
n
was added to the termini of linearized vector. Thus, we constructed an autonomously replicating linear vector having ten
repeats of the telomere-like sequence at both ends. The vector transformed the yeast cells with high transformation efficiency
(3230 CFU/μg of DNA), which was approximately 25-fold higher than that of a control vector lacking the repeats, and was autonomously
replicated at a roughly constant size. The copy number was estimated to be less than one copy, and Ura+ mitotic stability varied widely among the transformants and was related to plasmid segregation efficiency. 相似文献
569.
570.
Miyashita S Tadokoro T Angkawidjaja C You DJ Koga Y Takano K Kanaya S 《FEBS letters》2011,585(14):2313-2317
Ribonuclease H3 from Bacillus stearothermophilus (Bst-RNase H3) has the N-terminal TBP-like substrate-binding domain. To identify the substrate binding site in this domain, the mutant proteins of the intact protein and isolated N-domain, in which six of the seventeen residues corresponding to those involved in DNA binding of TBP are individually mutated to Ala, were constructed. All of them exhibited decreased enzymatic activities and/or substrate-binding affinities when compared to those of the parent proteins, suggesting that the N-terminal domain of RNase H3 uses the flat surface of the β-sheet for substrate binding as TBP to bind DNA. This domain may greatly change conformation upon substrate binding. 相似文献