RNase H is involved in fundamental cellular processes and is responsible for removing the short stretch of RNA from Okazaki fragments and the long stretch of RNA from R-loops. Defects in RNase H lead to embryo lethality in mice and Aicardi-Goutieres syndrome in humans, suggesting the importance of RNase H. To date, RNase H is known to be a non-sequence-specific endonuclease, but it is not known whether it performs other functions on the structural variants of RNA:DNA hybrids. Here, we used Escherichia coli RNase H as a model, and examined its catalytic mechanism and its substrate recognition modes, using single-molecule FRET. We discovered that RNase H acts as a processive exoribonuclease on the 3′ DNA overhang side but as a distributive non-sequence-specific endonuclease on the 5′ DNA overhang side of RNA:DNA hybrids or on blunt-ended hybrids. The high affinity of previously unidentified double-stranded (ds) and single-stranded (ss) DNA junctions flanking RNA:DNA hybrids may help RNase H find the hybrid substrates in long genomic DNA. Our study provides new insights into the multifunctionality of RNase H, elucidating unprecedented roles of junctions and ssDNA overhang on RNA:DNA hybrids.
Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular characteristics. Vaginal MA is hypothesized to arise from the mesonephric remnants located in the lateral vaginal wall. A 52-year-old woman presented with vaginal bleeding. Physical examination revealed a protruding mass in the left vaginal wall. Pelvic magnetic resonance imaging revealed a 2.5-cm mass arising from the left upper vagina and extending posterolaterally to the extravaginal tissue. The punch biopsy was diagnosed as poorly differentiated adenocarcinoma. She received radical surgical resection. Histologically, the tumor displayed various architectural patterns, including compactly aggregated small tubules, solid cellular sheets, endometrioid-like glands and ducts, intraluminal micropapillae, cribriform structure, and small angulated glands accompanied by prominent desmoplastic stroma. The tubules and ducts possessed hyaline-like, densely eosinophilic intraluminal secretions. The tumor extended to the subvaginal soft tissue and had substantial perineural invasion. Immunostaining revealed positivity for the mesonephric markers, including GATA3, TTF1, and PAX2, while showing very focal and weak positivity for estrogen receptor and negativity for progesterone receptor. Additionally, we observed a complete absence of p53 immunoreactivity. Targeted sequencing analysis revealed that the tumor harbored both activating KRAS p.G12D mutation and truncating TP53 p.E286* mutation. A thorough review of the previous literature revealed that 4.5% (3/67) of vaginal/cervical MAs and 0.9% (1/112) of uterine/ovarian mesonephric-like adenocarcinomas harbor TP53 mutations, indicating that this is very uncommon in malignant mesonephric lesions. In summary, we presented a rare case of vaginal MA uniquely harboring pathogenic TP53 mutation, resulting in p53 aberration.
This research investigates the design process of free-form architecture to understand the design strategy and changing factors during the development phase and the cause for them. It is aimed to foresee the changing factors from the design process and to reduce design changes. It analyzes the design changes of free-form architecture based on projects with finalized documentation or under construction in South Korea. Many free-form shapes of the free-form architectures have to be adjusted to rigid-form in order to satisfy function and be economical to build. The research finds three patterns in design changes. First, from the factors for design changes: function, constructability, design, program add/subtract, efficiency, circulation; Function and Constructability are the higher factors compared with the rest. The two are the design changes suitable for actual usage and cost savings. Second, each project has different predominant factors for design changes as the degree of free-form is different. Contrary to initial expectation, the greater the degrees of free-form of the competition scheme, the higher the rate of Function among the factors for design changes. Constructability is higher when the degree of the free-form is less than others. It means that the lower the degree of the free-form, the more properly planned the space of the building is. Last, Constructability of free-form architecture is considered during the earlier design phase than definite-form, one by which the design changes by comparing 'Before fixed Space Program' (BSP) and ' After fixed Space Program' (ASP) design changes. The research would be helpful as a reference for setting up competition guidelines to reduce trial and error during the design process.
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