Devleopment and application of fluorescent nucleoside

令和2年度 京都大学化学研究所 スーパーコンピュータシステム 利用報告

G-quadruplexes as versatile scaffolds for catalysis

DNA is receiving attention as a useful biomaterial in a broad range of research fields beyond its classical role as a biopolymer for storage and delivery of genetic information. Based on its chemical and thermal stability and easy accessibility, a series of DNA-based hybrid catalysts have been developed and successfully applied to various asymmetric reactions in water. Besides the canonical Watson–Crick duplex, the G-quadruplex structure has been actively exploited as horseradish-peroxidase (HRP)-mimicking DNAzymes via specific complexation with hemin. G-quadruplexes also provide a fascinating scaffold to develop a switchable catalytic system. This review summarizes the beginning, progress, and prospects of the noncanonical DNA-based hybrid catalysts, focusing on the G-quadruplexes as versatile scaffolds for catalysis

Synthesis and application of a ¹⁹F-labeled fluorescent nucleoside as a dual-mode probe for i-motif DNAs

Because of their stable orientations and their minimal interference with native DNA interactions and folding, emissive isomorphic nucleoside analogues are versatile tools for the accurate analysis of DNA structural heterogeneity. Here, we report on a bifunctional trifluoromethylphenylpyrrolocytidine derivative (FPdC) that displays an unprecedented quantum yield and highly sensitive ¹⁹F NMR signal. This is the first report of a cytosine-based dual-purpose probe for both fluorescence and ¹⁹F NMR spectroscopic DNA analysis. FPdC and FPdC-containing DNA were synthesized and characterized; our robust dual probe was successfully used to investigate the noncanonical DNA structure, i-motifs, through changes in fluorescence intensity and ¹⁹F chemical shift in response to i-motif formation. The utility of FPdC was exemplified through reversible fluorescence switching of an FPdC-containing i-motif oligonucleotide in the presence of Ag(I) and cysteine

Prevalence and comorbidity of allergic diseases in preschool children

PurposeAllergic disease and its comorbidities significantly influence the quality of life. Although the comorbidities of allergic diseases are well described in adult populations, little is known about them in preschool children. In the present study, we aimed to assess the prevalence and comorbidity of allergic diseases in Korean preschool children.MethodsWe conducted a cross-sectional study comprising 615 Korean children (age, 3 to 6 years). Symptoms of allergic diseases were assessed using the Korean version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire that was modified for preschool children. Comorbidities of allergic diseases were assessed by 'In the last 12 months, has your child had symptoms?'.ResultsThe prevalence of symptoms of asthma, allergic rhinitis, and atopic dermatitis as recorded using the ISAAC questionnaire, within the last 12 months was 13.8%, 40.7%, and 20.8%, respectively. The symptom rates of allergic conjunctivitis, food allergy, and drug allergy were 14.8%, 10.4%, and 0.8%, respectively. The prevalence of allergic rhinitis in children with asthma was 64.3% and that of asthma in children with allergic rhinitis was 21.6%. The prevalence of rhinitis in children with conjunctivitis was 64.8% and that of conjunctivitis in children with rhinitis was 23.6%.ConclusionThe prevalence of current rhinitis in our preschool children is shown to be higher than that previously reported. Allergic conjunctivitis is closely associated with asthma and allergic rhinitis. However, further studies are warranted to determine the prevalence and effects of these comorbidities on health outcomes in preschool children

Food allergen sensitization in young children with typical signs and symptoms of immediate-type food allergies: a comparison between monosensitized and polysensitized children

PurposeThe clinical interpretation of children sensitized to allergens is challenging, particularly in children with food allergies. We aimed to examine clinical differences between children with monosensitization and those with polysensitization to common food allergens and to determine risk factors for polysensitization in young children <10 years of age with immediate-type food allergies.MethodsThe study included children <10 years of age with signs and symptoms indicative of immediate-type food allergies. Serum total IgE level was measured, and ImmunoCAP analysis for food allergens was performed.ResultsThe mean age of the study subjects was 1.6±1.6 years (75 boys and 51 girls). Thirty-eight children (30.2%) were monosensitized and 88 children (69.8%) were polysensitized. Multivariate logistic regression analysis showed that the development of polysensitization to common food allergens was positively associated with a parental history of allergic rhinitis (adjusted odds ratio [aOR], 6.28; 95% confidence interval [CI], 1.78-22.13; P=0.004), season of birth (summer/fall) (aOR, 3.10; 95% CI, 1.10-8.79; P=0.033), and exclusive breastfeeding in the first 6 months of age (aOR, 3.51; 95% CI, 1.20-10.25; P=0.022).ConclusionWe found significant clinical differences between children with monosensitization and those with polysensitization to common food allergens and identified risk factors for the development of polysensitization in young children with immediate-type food allergies. Clinicians should consider these clinical risk factors when evaluating, counseling, treating, and monitoring young children with food allergies

Nusinersen demonstrates effectiveness in treating spinal muscular atrophy: findings from a three-year nationwide study in Korea

IntroductionNusinersen is the first drug approved for spinal muscular atrophy (SMA) treatment. In this study, we aimed to evaluate the long-term safety and efficacy of nusinersen, assess the therapeutic effects based on the treatment initiation timing and baseline motor function, and explore the perception of functional improvement from either parents or patients, utilizing 3-year nationwide follow-up data in South Korea.MethodsWe enrolled patients with SMA who were treated with nusinersen under the National Health Insurance coverage, with complete motor score records available and a minimum treatment duration of 6 months. To evaluate the motor function of patients, the Hammersmith Infant Neurological Examination-2 (HINE-2) was used for type 1 and the Expanded Hammersmith Functional Motor Scale (HFMSE) was used for types 2 and 3 patients. A significant improvement was defined as a HINE-2 score gain ≥5 for patients with type 1 and an HFMSE score ≥ 3 for patients with types 2 and 3 SMA. Effects of treatment timing were assessed. Patients with type 2 were further categorized based on baseline motor scores for outcome analysis. We also analyzed a second dataset from five tertiary hospitals with the information on parents/patients-reported impressions of improvement.ResultsThe study comprised 137 patients, with 21, 103, and 13 patients representing type 1, 2, and 3 SMA, respectively. At the 3-year follow-up, the analysis encompassed 7 patients with type 1, 12 patients with type 2, and none with type 3. Nearly half of all enrolled patients across SMA types (42.8, 59.2 and 46.2%, respectively) reached the 2-year follow-up for analysis. Patients with type 1 SMA exhibited gradual motor function improvement over 1-, 2-, and 3-year follow-ups (16, 9, and 7 patients, respectively). Patients with type 2 SMA demonstrated improvement over 1-, 2-, and 3-year follow-ups (96, 61 and 12 patients, respectively). Early treatment from symptom onset resulted in better outcomes for patients with type 1 and 2 SMA. In the second dataset, 90.7% of 108 patients reported subjective improvement at the 1-year follow-up.ConclusionNusinersen treatment for types 1–3 SMA is safe and effective in long-term follow-up. Early treatment initiation was a significant factor affecting long-term motor outcome

A Nationwide Survey of Lymphangioleiomyomatosis in Korea: Recent Increase in Newly Diagnosed Patients

In 2007, the Korean Interstitial Lung Disease Society had collected clinical data of patients who have diagnosed as Lymphangioleiomyomatosis (LAM) since 1990 through nationwide survey, which showed that LAM patients had increased sharply after 2004. The present study was performed to show the clinical features of Korean patients with LAM, and to establish the reason for the recent increase in the diagnosis. All 63 patients were women and the mean age at diagnosis was 36 yr. The most common presenting symptom was dyspnea and 8 patients had tuberous sclerosis complex. The survival rate at 5 yr after diagnosis was 84%. Compared with patients diagnosed after 2004 (n=34), the patients diagnosed before 2004 (n=29) complained with dyspnea more (P=0.016) and had lower FEV1% predicted (P=0.003), and DLco% predicted (P=0.042). The higher proportion of patients diagnosed after 2004 showed the normal chest radiography, and they were detected by routine chest CT screening (P=0.016). This study showed that clinical features of Korean patients with LAM were not different from those reported elsewhere. It is concluded that the reason for the increase of newly diagnosed patients is the result of increase in detection of the early stage LAM by the widespread use of chest CT screening

The Korea–United States Air Quality (KORUS-AQ) field study

The Korea–United States Air Quality (KORUS-AQ) field study was conducted during May–June 2016. The effort was jointly sponsored by the National Institute of Environmental Research of South Korea and the National Aeronautics and Space Administration of the United States. KORUS-AQ offered an unprecedented, multi-perspective view of air quality conditions in South Korea by employing observations from three aircraft, an extensive ground-based network, and three ships along with an array of air quality forecast models. Information gathered during the study is contributing to an improved understanding of the factors controlling air quality in South Korea. The study also provided a valuable test bed for future air quality–observing strategies involving geostationary satellite instruments being launched by both countries to examine air quality throughout the day over Asia and North America. This article presents details on the KORUS-AQ observational assets, study execution, data products, and air quality conditions observed during the study. High-level findings from companion papers in this special issue are also summarized and discussed in relation to the factors controlling fine particle and ozone pollution, current emissions and source apportionment, and expectations for the role of satellite observations in the future. Resulting policy recommendations and advice regarding plans going forward are summarized. These results provide an important update to early feedback previously provided in a Rapid Science Synthesis Report produced for South Korean policy makers in 2017 and form the basis for the Final Science Synthesis Report delivered in 2020

高度な特性を有するモジュラーDNAのバイオハイブリッド触媒及びアプタマーとしての応用

京都大学新制・課程博士博士(理学)甲第23736号理博第4826号新制||理||1690(附属図書館)京都大学大学院理学研究科化学専攻(主査)教授 杉山 弘, 教授 深井 周也, 教授 秋山 芳展学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDGA