RESUMO
Trinucleotide repeat (TNR) sequences, which are responsible for several neurodegenerative genetic diseases, fold into hairpins that interfere with the protein machinery in replication or repair, thus leading to dynamic mutation -abnormal expansions of the genome. Despite their high thermodynamic stability, these hairpins can undergo configurational rearrangements, which may be crucial for continuous dynamic mutation. Here, we used CTG repeats as a model system to study their structural dynamics at the single-molecule level. A unique dynamic two-state configuration interchange was discovered over a wide range of odd-numbered CTG repeat sequences. Employing repeat-number-dependent kinetic analysis, we proposed a bulge translocation model, which is driven by the local instability and can be extended reasonably to longer (pathologically relevant) hairpins, implying the potential role in error accumulation in repeat expansion.
Assuntos
DNA/química , DNA/genética , Conformação de Ácido Nucleico , Repetições de Trinucleotídeos/genética , Simulação de Dinâmica Molecular , Método de Monte Carlo , TermodinâmicaRESUMO
The purpose of this study was to evaluate the accuracy of dual-axis rotational coronary angiography (DARCA) for coronary lesion assessment by directly comparing with intravascular ultrasound (IVUS). From October 2014 to December 2015, 40 patients (58 lesions) who had undergone both DARCA and IVUS were included in the image analysis. The minimum lumen diameter (MLD), lesion length, reference vessel diameter (RVD) and percent diameter stenosis at the same lesion, were identified and assessed. Significant correlation with IVUS was found for DARCA in either lesion length (r = 0.90, P < 0.001) or RVD (r = 0.81, P < 0.001) comparison. DARCA had fair correlation with IVUS for both MLD (r = 0.65, P < 0.001) and diameter stenosis (r = 0.48, P < 0.001). From the Bland-Altman plots, there was a good agreement between DARCA and IVUS regarding MLD (mean difference: -0.23 mm, 95 % limits of agreement: -0.96 to 0.50 mm) and RVD (mean difference: -0.15 mm, 95 % limits of agreement: -0.85 to 0.55 mm), while lesser agreement was found on lesion length (mean difference: -3.39 mm, 95 % limits of agreement: -12.63 to 5.85 mm) and diameter stenosis (mean difference: 4.82 %, 95 % limits of agreement: -17.05 to 26.68 %). There is an adequate correlation and agreement between DARCA and IVUS in coronary lesion assessment.