Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DNA is continuously damaged by endogenous and exogenous factors such as oxidation and alkylation. In the base excision repair pathway, the damaged nucleobases are removed by DNA N-glycosylase to form the abasic sites (AP sites). The alkylating antitumor agent exhibits cytotoxicity through the formation of the AP site. Therefore blockage or modulation of the AP site repair pathway may enhance the antitumor efficacy of DNA alkylating agents. In this study, we have examined the effects of the nucleobase-polyamine conjugated ligands (G-, A-, C- and T-ligands) on the cleavage of the AP site. The G- and A-ligands cleaved DNA at the AP site by promoting β-elimination in a non-selective manner by the G-ligand, and in a selective manner for the opposing dT by the A-ligand. These results suggest that the nucleobase-polyamine conjugate ligands may have the potential for enhancement of the cytotoxicities of the AP site.

Language：English   Publishing type：Research paper (scientific journal)  

DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3’-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; i.e., A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site.

Language：English   Publisher：Scientific Reports  

Prompt personal identification is required during disasters that can result in many casualties. To rapidly estimate sex based on skull structure, this study applied deep learning using two-dimensional silhouette images, obtained from head postmortem computed tomography (PMCT), to enhance the outline shape of the skull. We investigated the process of sex estimation using silhouette images viewed from different angles and majority votes. A total of 264 PMCT cases (132 cases for each sex) were used for transfer learning with two deep-learning models (AlexNet and VGG16). VGG16 exhibited the highest accuracy (89.8%) for lateral projections. The accuracy improved to 91.7% when implementing a majority vote based on the results of multiple projection angles. Moreover, silhouette images can be obtained from simple and popular X-ray imaging in addition to PMCT. Thus, this study demonstrated the feasibility of sex estimation by combining silhouette images with deep learning. The results implied that X-ray images can be used for personal identification.

DOI： 10.1038/s41598-024-74703-y

Scopus

PubMed

Publisher：Organic and Biomolecular Chemistry  

We designed 6-dimethylamino 3-methyleneisoindolin-1-one as an environment-sensitive fluorophore, examining its applications for protein labeling. Synthesized 3-methyleneisoindolin-1-one exhibits solvatochromic fluorescence (λemmax; 472 nm in 2-PrOH, 512 nm in H2O). A positive linear dependence between λemmax and solvent dielectric constant (DC), as well as between Stokes shift and DC, and a negative correlation between fluorescence quantum yield and DC are observed in protic solvents. These properties are similar to those of the oxygen isosteric fluorophore, 4-dimethylaminophthalimide, a slovatochromic fluorophore utilized for labeling oligodeoxynucleotides (ODNs) and peptides. Notably, fluorescence intensity of 3-methyleneisoindolin-1-one is higher than the phthalimide in protic solvents used in this study. The 3-methyleneisoindolin-1-one demonstrated the higher stability in pH 8 solution than in pH 6 solution in contrast to the stability profile of the phthalimide, which was stable at pH 6 but was hydrolyzed at pH 8. We also synthesized an o-keto benzaldehyde derivative that converts a primary amine to 6-dimethylamino 3-methyleneisoindolin-1-one under biocompatible conditions and introduced it into ODNs for turn-on fluorescent protein labeling. The synthesized ODN with a protein-binding sequence of Escherichia coli DnaA was employed to modify the DNA-binding domain of DnaA, and the fluorescent properties of the modified protein were investigated.

DOI： 10.1039/d4ob01036a

Scopus

Event date： 2013.3

Language：Japanese  

Venue：横浜   Country：Japan  

Event date： 2010.12

Language：English  

Venue：Hawaii   Country：United States  

Event date： 2010.11

Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：横浜   Country：Japan  

Event date： 2020.9

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：オンライン   Country：Japan  

Event date： 2019.11

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：長崎大学文教キャンパス   Country：Japan