The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China.
Amino Acid Sequence ; Base Sequence ; Capsid Proteins ; chemistry ; genetics ; China ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phylogeny ; Poliomyelitis ; virology ; Poliovirus ; chemistry ; genetics ; metabolism ; Poliovirus Vaccines ; adverse effects ; chemistry ; genetics ; metabolism ; Sequence Alignment

Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.
Adenine ; chemistry ; metabolism ; Amino Acid Sequence ; Binding Sites ; DNA ; chemistry ; metabolism ; DNA-Binding Proteins ; chemistry ; metabolism ; Guanine ; chemistry ; metabolism ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary

Objective:To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and central lymph node metastasis (CLNM) in patients with cN0 papillary thyroid microcarcinoma (PTMC).Methods:The clinicopathological data of PTMC patients confirmed by surgery and pathology in the 81 st Military Hospital of People′s Liberation Army from 2016 to 2019 were collected, and the relationship between preoperative NLR, PLR levels and postoperative PTMC CLNM were analyzed. Logistic regression analysis was used for multivariate analysis. Receiver operating characteristic (ROC) curve was used to determine the cutoff value of NLR and PLR. The interaction relative excess risk was used to analyze the relationship between NLR, PLR and CLNM. Results:Among 220 patients with cN0 stage PTMC, 92 were CLNM. The ROC curve showed that when the cutoff value of NLR was 2.5 and the cutoff value of PLR was 175, the highest Youden index was 0.318 and 0.264, respectively. NLR and PLR were both related to CLNM ( P<0.05). The tumor long diameter, multifocality, NLR≥2.5 and PLR≥175 were independent impact factors of CLNM ( P<0.05). The results of the interaction showed that the relative excess risk of the interaction was 5.531 (95% CI: 0.160, 10.901, P=0.016), the attribution ratio was 0.512 (95% CI: 0.230, 0.794, P=0.009), and the synergy index was 2.294 (95% CI: 1.492, 4.579, P=0.022), suggested that NLR and PLR had an interactive effect, and these two synergistically promoted CLNM. Conclusions:NLR and PLR are independent risk factors for cN0 stage PTMC CLNM. When NLR≥2.5 and PLR≥175, preventive central lymph node dissection should be routinely performed.

Objective:To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and central lymph node metastasis (CLNM) in patients with cN0 papillary thyroid microcarcinoma (PTMC).Methods:The clinicopathological data of PTMC patients confirmed by surgery and pathology in the 81 st Military Hospital of People′s Liberation Army from 2016 to 2019 were collected, and the relationship between preoperative NLR, PLR levels and postoperative PTMC CLNM were analyzed. Logistic regression analysis was used for multivariate analysis. Receiver operating characteristic (ROC) curve was used to determine the cutoff value of NLR and PLR. The interaction relative excess risk was used to analyze the relationship between NLR, PLR and CLNM. Results:Among 220 patients with cN0 stage PTMC, 92 were CLNM. The ROC curve showed that when the cutoff value of NLR was 2.5 and the cutoff value of PLR was 175, the highest Youden index was 0.318 and 0.264, respectively. NLR and PLR were both related to CLNM ( P<0.05). The tumor long diameter, multifocality, NLR≥2.5 and PLR≥175 were independent impact factors of CLNM ( P<0.05). The results of the interaction showed that the relative excess risk of the interaction was 5.531 (95% CI: 0.160, 10.901, P=0.016), the attribution ratio was 0.512 (95% CI: 0.230, 0.794, P=0.009), and the synergy index was 2.294 (95% CI: 1.492, 4.579, P=0.022), suggested that NLR and PLR had an interactive effect, and these two synergistically promoted CLNM. Conclusions:NLR and PLR are independent risk factors for cN0 stage PTMC CLNM. When NLR≥2.5 and PLR≥175, preventive central lymph node dissection should be routinely performed.