Multiple consecutive initiation of replication producing novel brush-like intermediates at the termini of linear viral dsDNA genomes with hairpin ends.
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ABSTRACT:
SUBMITTER: Martinez-Alvarez L
PROVIDER: S-EPMC5062984 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Agrobacterium tumefaciens C58, the pathogenic bacteria that causes crown gall disease in plants, harbors one circular and one linear chromosome and two circular plasmids. The telomeres of its unusual linear chromosome are covalently closed hairpins. The circular and linear chromosomes co-segregate and are stably maintained in the organism. We have determined the sequence of the two ends of the linear chromosome thus completing the previously published genome sequence of A. tumefaciens C58. We found that the telomeres carry nearly identical 25-bp sequences at the hairpin ends that are related by dyad symmetry. We further showed that its Atu2523 gene encodes a protelomerase (resolvase) and that the purified enzyme can generate the linear chromosomal closed hairpin ends in a sequence-specific manner. Agrobacterium protelomerase, whose presence is apparently limited to biovar 1 strains, acts via a cleavage-and-religation mechanism by making a pair of transient staggered nicks invariably at 6-bp spacing as the reaction intermediate. The enzyme can be significantly shortened at both the N and C termini and still maintain its enzymatic activity. Although the full-length enzyme can uniquely bind to its product telomeres, the N-terminal truncations cannot. The target site can also be shortened from the native 50-bp inverted repeat to 26 bp; thus, the Agrobacterium hairpin-generating system represents the most compact activity of all hairpin linear chromosome- and plasmid-generating systems to date. The biochemical analyses of the protelomerase reactions further revealed that the tip of the hairpin telomere may be unusually polymorphically capable of accommodating any nucleotide.
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Project description:IntroductionThe aim of this study was to determine whether Electronic Nicotine Delivery Systems (ENDS) device type (disposable devices, replaceable cartridges, and refillables) at initial or first ENDS use predicts subsequent initiation of combustible tobacco products (cigarettes, hookah, cigars) among adolescents and/or differentiates between those who initiate use of both ENDS and combustible tobacco products at the same time.MethodsThe study examined data from the Texas Adolescent Tobacco and Marketing Surveillance System (TATAMS), a longitudinal population-based cohort of students in major metropolitan areas of Texas (n = 3907; N = 461 069). Data were collected every 6 months, from 2014 to 2018; 33.9% (n = 1324; N = 151 784) of the sample initiated ENDS use across this period. Unadjusted and adjusted logistic regression models were used to assess the odds of initiating combustible tobacco products at a subsequent or similar wave as ENDS initiation, given initial ENDS device type.ResultsAfter adjusting for sociodemographic factors, the odds of initiating combustible tobacco use subsequent to ENDS initiation were significantly lower among those who reported using Cartridges as their initial device type compared to those who reported Refillables as their initial device type (adjusted odds ratio = 0.42 [0.18-0.98], p = .05). In addition, after controlling for sociodemographic variables, the odds of initiating combustible tobacco use in the same wave as ENDS initiation were significantly higher among those who reported using Cartridges as their initial device type, compared with those who reported Refillables as their initial device type (adjusted odds ratio = 2.31 [1.05-5.10], p = .04). No significant differences were found in adjusted models when Disposables were compared to Refillables and Cartridges to Disposables.ConclusionENDS device type differentiates between adolescents who start using combustible tobacco products at the same time as initial ENDS use, or subsequently.ImplicationsPrevious research has shown ENDS use predicts subsequent combustible use among adolescents, but there is lack of research on the role of specific ENDS device types and the timing of initiation. Findings from this longitudinal study show that initiation of combustible tobacco product use varies by initial ENDS device type among adolescents. These findings can become a focal point for developing interventions for adolescents and could have regulatory implications for ENDS products.
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