Revealing conformational dynamics of 2′- O -methyl-RNA guanine modified G-quadruplex by replica exchange molecular dynamics

Abstract(#br)Thrombin-binding DNA aptamer (TBA) can fold into an antiparallel unimolecular G-quadruplex (G4) structure. Different types of modifications lead to various effects on the structure and stability of the G4 structure. Previous study has shown that a modified TBA (mTBA) that 2′-deoxy guanine (dG) at positions 10 and 11 in the TBA sequence were replaced by 2′- O -methyl-RNA guanine (2′OMe-G) can’t fold into a well-defined G4 structure. In order to investigate the detailed structural information and probe the instability factors, we successfully employed the replica exchange molecular dynamics (REMD) to characterize the large conformational variations of the mTBA and systemically describe the influences of the 2′OMe-G on the mTBA in terms of conformation variations and the probability distributions of Hoogsteen hydrogen bonds, dihedral, sugar pucker and glycosyl torsion angle. Replacing position 10 with the 2′OMe-G (2′OMe-G10) induced a strong destabilization of the aptamer, while the 2′OMe-G at position 11(2′OMe-G11) was less destabilizing. More importantly, the glycosyl torsion angle and sugar pucker of 2′OMe-G10 were the most critical destabilization factors. These results were in good agreement with the theoretical and experimental results. Moreover, the structure information can be used as guidelines for the further design of modifications on G4 structure

Revealing conformational dynamics of 2'-O-methyl-RNA guanine modified G-quadruplex by replica exchange molecular dynamics.

Thrombin-binding DNA aptamer (TBA) can fold into an antiparallel unimolecular G-quadruplex (G4) structure. Different types of modifications lead to various effects on the structure and stability of the G4 structure. Previous study has shown that a modified TBA (mTBA) that 2’-deoxy guanine (dG) at positions 10 and 11 in the TBA sequence were replaced by 2’-O-methyl-RNA guanine (2’OMe-G) can’t fold into a well-defined G4 structure. In order to investigate the detailed structural information and probe the instability factors, we successfully employed the replica exchange molecular dynamics (REMD) to characterize the large conformational variations of the mTBA and systemically describe the influences of the 2’OMe-G on the mTBA in terms of conformation variations and the probability distributions of Hoogsteen hydrogen bonds, dihedral, sugar pucker and glycosyl torsion angle. Replacing position 10 with the 2’OMe-G (2’OMe-G10) induced a strong destabilization of the aptamer, while the 2’OMe-G at position 11(2’OMe-G11) was less destabilizing. More importantly, the glycosyl torsion angle and sugar pucker of 2’OMe-G10 were the most critical destabilization factors. These results were in good agreement with the theoretical and experimental results. Moreover, the structure information can be used as guidelines for the further design of modifications on G4 structure

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Genome-wide DNA polymorphisms in two cultivars of mei (Prunus mume sieb. et zucc.)

BACKGROUND: Mei (Prunus mume Sieb. et Zucc.) is a famous ornamental plant and fruit crop grown in East Asian countries. Limited genetic resources, especially molecular markers, have hindered the progress of mei breeding projects. Here, we performed low-depth whole-genome sequencing of Prunus mume ‘Fenban’ and Prunus mume ‘Kouzi Yudie’ to identify high-quality polymorphic markers between the two cultivars on a large scale. RESULTS: A total of 1464.1 Mb and 1422.1 Mb of ‘Fenban’ and ‘Kouzi Yudie’ sequencing data were uniquely mapped to the mei reference genome with about 6-fold coverage, respectively. We detected a large number of putative polymorphic markers from the 196.9 Mb of sequencing data shared by the two cultivars, which together contained 200,627 SNPs, 4,900 InDels, and 7,063 SSRs. Among these markers, 38,773 SNPs, 174 InDels, and 418 SSRs were distributed in the 22.4 Mb CDS region, and 63.0% of these marker-containing CDS sequences were assigned to GO terms. Subsequently, 670 selected SNPs were validated using an Agilent’s SureSelect solution phase hybridization assay. A subset of 599 SNPs was used to assess the genetic similarity of a panel of mei germplasm samples and a plum (P. salicina) cultivar, producing a set of informative diversity data. We also analyzed the frequency and distribution of detected InDels and SSRs in mei genome and validated their usefulness as DNA markers. These markers were successfully amplified in the cultivars and in their segregating progeny. CONCLUSIONS: A large set of high-quality polymorphic SNPs, InDels, and SSRs were identified in parallel between ‘Fenban’ and ‘Kouzi Yudie’ using low-depth whole-genome sequencing. The study presents extensive data on these polymorphic markers, which can be useful for constructing high-resolution genetic maps, performing genome-wide association studies, and designing genomic selection strategies in mei

Determinants of depression, problem behavior, and cognitive level of adolescents in China: Findings from a national, population-based cross-sectional study

IntroductionWe aimed to assess the associated factors for adolescent depression, problem behavior and cognitive level in China.MethodsA total of 2,584 adolescents aged from 10 to 15 years old in 2018 were included for analyses. Information on a comprehensive set of potential determinants was collected by the questionnaire, including demographic, health-, school- and family-related factors. Differences in average scores of depression, problem behavior, and cognitive level across subgroups were assessed by two independent sample t-tests and one-way analysis of variance (ANOVA). The clinical relevance among subgroups was assessed by the effect size. Multivariate linear regression models were applied to identify the statistically significant determinants.ResultsSchool-related factors and parental depressive status were strongly associated with depression. Low maternal education, poor/bad health of adolescents, high academic pressure, and parental depression were significantly associated with behavior problems. The socioeconomic factors, poor academic performance and father’s depression were significantly associated with adolescent cognitive level.DiscussionMultiple associated factors were identified for depression, problem behavior, and cognition of Chinese adolescents, which will provide insights into developing more targeted public health policies and interventions to improve their mental health