The homeobox transcription factor DUXBL controls exit from totipotency.

In mice, exit from the totipotent two-cell (2C) stage embryo requires silencing of the 2C-associated transcriptional program. However, the molecular mechanisms involved in this process remain poorly understood. Here we demonstrate that the 2C-specific transcription factor double homeobox protein (DUX) mediates an essential negative feedback loop by inducing the expression of DUXBL to promote this silencing. We show that DUXBL gains accessibility to DUX-bound regions specifically upon DUX expression. Furthermore, we determine that DUXBL interacts with TRIM24 and TRIM33, members of the TRIM superfamily involved in gene silencing, and colocalizes with them in nuclear foci upon DUX expression. Importantly, DUXBL overexpression impairs 2C-associated transcription, whereas Duxbl inactivation in mouse embryonic stem cells increases DUX-dependent induction of the 2C-transcriptional program. Consequently, DUXBL deficiency in embryos results in sustained expression of 2C-associated transcripts leading to early developmental arrest. Our study identifies DUXBL as an essential regulator of totipotency exit enabling the first divergence of cell fates.

Preptin promotes proliferation and osteogenesis of MC3T3-E1 cells by upregulating ß-catenin expression.

Preptin, an oligopeptide secreted by pancreatic ß-cell, plays a significant role in glycometabolism and bone metabolism. Preptin strengthens proliferation and differentiation of osteoblasts, but the mechanism is unclear. Here, we explored the role of the Wnt/ß-catenin signaling pathway which is well known to affect bone development and remodelling in the function of preptin. We found that preptin promoted the cell proliferative activity and osteoblastic differentiation in osteoblast-like MC3T3-E1 cells in a dose-independent manner, as evidenced by elevation in osteogenic genes, alkaline phosphatase activity and alizarin red staining in a dose-independent manner. Additionally, our findings demonstrated that the ß-catenin expression level and runt-related transcription factor 2, which is the key downstream target of this pathway, were increased. The Wnt/ß-catenin signalling pathway antagonist DKK1 abrogated the proliferative effect and differentiation function of preptin in MC3T3-E1 cells. These data indicated that preptin may be a potential therapeutic target for the treatment of osteoporosis and that osteogenic impact of preptin in MC3T3-E1 cells might be mediated by the Wnt/ß-catenin signalling pathway. © 2019 IUBMB Life, 9999(9999):1-9, 2019.

[The Antimicrobial Resistance Analysis of 73 Strains of Streptococcus pneumoniae Isolated from Infant Respiratory Tract].

OBJECTIVE: To preliminary study of the resistance mechanisms of S. pneumoniae (S. pn) by determining the resistance rates and gene of S. pn isolated from the lower respiratory tract infection infants. METHODS: Drug susceptibility test with disk diffusion and broth micro-dilution was conducted to evaluate the resistance rates of 73 strains of S. pn isolated from the lower respiratory tract infection infants to penicillin, levofloxacin and other 10 antibiotics. PCR method was used to analysis the antimicrobial resistant genes tet M, mef A, erm A, erm B and int Tn of the isolates. RESULTS: The antibiotic resistance rates of the S. pn isolates to erythromycin, clindamycin and tetracycline were 95. 9%, 94. 5%, 87. 7% and 0% to vancomycin when tested with disk diffusion method. The antibiotic resistance rates of these isolates to penicillin, cefotaxime and ceftriaxone were 45. 2%, 47. 9% and 46. 6% respectively when tested with broth micro-dilution method. The carrier frequencies of tet M, mef A, erm A, erm B, int Tn genes in the 73 isolates were 91. 8%, 63. 0%, 58. 9%, 39. 7% and 61. 6% respectively. CONCLUSION: The S. pn strains isolated from infant respiratory tract in Chengdu perform a serious drug resistance problem, especially to routine antibiotics like erythromycin, clindamycin and tetracycline and cephalosporin, the resistance rate to levofloxacin, chloramphenicol remained at a low level; the resistance to tetracycline was closely related with the tet M gene fragment, the resistance to macrolide was mainly decided by active efflux pump and secondarily by the alternation of gene targeting, int Tn had close relation with tet M, erm B.

[Sequence analysis of G glycoprotein gene of human respiratory syncytial virus].

OBJECTIVE: To understand the variation of G glycoprotein gene of human respiratory syncytial virus (HRSV) obtained from Sichuan in 2010 and determine the dominant genotypes. METHODS: G glycoprotein gene of seven cases of subtype A and eleven cases of subtype B of HRSV were amplified by RT-PCR and sequenced. The phylogenetic trees were constructed to determine the subtype of samples. And then, the genetic variations of the second hypervariable region of G glycoprotein gene were studied. RESULTS: The nucleotide genetic distances of G glycoprotein gene in subtype A and subtype B HRSV were 0.022 +/- 0.005 and 0.073 +/- 0.010, respectively. Transitions were more prevalent than transversions, GA -AG were the most frequent transitions detected among group A viruses, while UC+CU transitions were the most among group B. Phylogenetic analyses demonstrated that 7 subtype A virus could be clustered into one genotype, genotype GA2, and 11 subtype B virus could be clustered into two genotypes, GB2 and BA. The length of G protein gene in group A was all 298aa, but in group B included 295aa, 312aa and 315aa. Selective pressure was purifying selection in both subtypes. 9 positively selected sites in group A and 1 in group B on the second hypervariable region of G protein were identified. CONCLUSION: GA2, GB2 and BA were the main genotype. The changes may favor virus escape from the host immune response including the variation of the G protein gene length, frequency of nucleotide changes and selective pressure.