Efflux-mediated fluoroquinolone resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7: identification of a novel MexS variant involved in upregulation of the mexEF-oprN multidrug efflux operon

The emergence of multidrug-resistant Pseudomonas aeruginosa has become a serious problem in medical settings. P. aeruginosa clinical isolate PA7 is resistant to fluoroquinolones, aminoglycosides, and most -lactams but not imipenem. In this study, enhanced efflux-mediated fluoroquinolone resistance of PA7 was shown to reflect increased expression of two resistance nodulation cell division (RND) -type multidrug efflux operons, mexEF-oprN and mexXY-oprA. Such a clinical isolate has rarely been reported because MexEF-OprN-overproducing mutants often increase susceptibility to aminoglycosides apparently owing to impairment of the MexXY system. A mutant of PA7 lacking three RND-type multidrug efflux operons (mexAB-oprM, mexEF-oprN, and mexXY-oprA) was susceptible to all anti-pseudomonas agents we tested, supporting an idea that these RND-type multidrug efflux transporters are molecular targets to overcome multidrug resistance in P. aeruginosa. mexEF-oprN-upregulation in P. aeruginosa PA7 was shown due to a MexS variant harboring the Valine-155 amino acid residue. This is the first genetic evidence shown that a MexS variant causes mexEF-oprN-upregulation in P. aeruginosa clinical isolates

Vascular Senescence in Chronic kidney Disease; Association of Aryl Hydrocarbon Receptor Activated by Indoxyl Sulfate

The impact of chronic kidney disease (CKD) on the occurrence of cardiovascular disease (CVD) is a major concern and this reciprocal relation is currently so called "cardio-renal syndrome". More detailed understanding in its mechanism may have a possibility to reduce the global burden of CVD. Of note, uremic toxins have been known to accumulate in the progression of CKD and play an important role for worsening renal function, on the other hand, recent studies suggest that they also negatively affect cardiovascular system. In this review, we delve into the role of aryl hydrocarbon receptor (AhR) in uremic toxicities, as highlighted in our latest work and give a new insight for the mechanism of cardio-renal syndrome

高等真核生物における細胞表面タンパク質のリガンド認識の分子基盤

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 飯野 雄一, 東京大学教授 福田 裕穂, 東京大学准教授 伊藤 恭子, 東京大学教授 濡木 理, 東京大学准教授 大戸 梅治, 東京大学准教授 深井 周也University of Tokyo(東京大学

Activation of strigolactone biosynthesis by the DWARF14-LIKE/KARRIKIN-INSENSITIVE2 pathway in mycorrhizal angiosperms, but not in Arabidopsis, a non-mycorrhizal plant

Strigolactones (SLs) are a class of plant hormones that regulate many aspects of plant growth and development. SLs also improve symbiosis with arbuscular mycorrhizal fungi (AMF) in the rhizosphere. Recent studies have shown that the DWARF14-LIKE (D14L)/KARRIKIN-INSENSITIVE2 (KAI2) family, paralogs of the SL receptor D14, are required for AMF colonization in several flowering plants, including rice. In this study, we found that (−)-GR5, a 2′S-configured enantiomer of a synthetic SL analog (+)-GR5, significantly activated SL biosynthesis in rice roots via D14L. This result is consistent with a recent report, showing that the D14L pathway positively regulates SL biosynthesis in rice. In fact, the SL levels tended to be lower in the roots of the d14l mutant under both inorganic nutrient-deficient and -sufficient conditions. We also show that the increase in SL levels by (−)-GR5 was observed in other mycorrhizal plant species. In contrast, the KAI2 pathway did not upregulate the SL level and the expression of SL biosynthetic genes in Arabidopsis, a non-mycorrhizal plant. We also examined whether the KAI2 pathway enhances SL biosynthesis in the liverwort Marchantia paleacea, where SL functions as a rhizosphere signaling molecule for AMF. However, the SL level and SL biosynthetic genes were not positively regulated by the KAI2 pathway. These results imply that the activation of SL biosynthesis by the D14L/KAI2 pathway has been evolutionarily acquired after the divergence of bryophytes to efficiently promote symbiosis with AMF, although we cannot exclude the possibility that liverworts have specifically lost this regulatory system

下部直腸癌におけるMRIを用いた歯状線浸潤の診断精度

Purpose: To retrospectively assess the accuracy of magnetic resonance imaging (MRI) in predicting dentate line invasion in low rectal cancer. Materials and methods: Eighty-one patients with primary rectal cancer were assessed by dynamic contrast-enhanced MRI. The location of the dentate line was assessed on MRI in 27 patients with upper-mid rectal cancer. Two observers independently evaluated the distance between the distal tumor edge and the MRI-defined dentate line in 54 patients with low rectal cancer, and the imaging and histological findings were compared. Results: The MRI-defined dentate line was 24.0 ± 3.8 mm above the anal verge in patients with upper-mid rectal cancer. The dentate line invasion status agreed with the histological findings in 49/54 (91%) patients (κ = 0.72 [95% CI 0.50-0.95]) for observer 1, and in 51/54 (94%) patients (κ = 0.83 [0.65-1.00]) for observer 2 in patients with low rectal cancer. Interobserver agreement was good (κ = 0.83 [0.65-1.00]). The MRI-derived distance between the distal tumor edge and the dentate line had significant correlation with the histological distance (r = 0.86 for reader 1 and 0.75 for observer 2). Conclusion: MRI demonstrates high accuracy in predicting dentate line invasion in low rectal cancer.博士（医学）・甲第748号・令和2年6月30日© Japan Radiological Society 2020© 2020 Springer Nature Switzerland AG. Part of Springer Nature.This is a post-peer-review, pre-copyedit version of an article published in Japanese journal of radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s11604-020-00933-5

Behavioral factors to include in guidelines for lifelong oral healthiness: an observational study in Japanese adults

BACKGROUND: The aim of this study was to determine which behavioral factors to include in guidelines for the Japanese public to achieve an acceptable level of oral healthiness. The objective was to determine the relationship between oral health related behaviors and symptoms related to oral disease and tooth loss in a Japanese adult community. METHODS: Oral health status and lifestyle were investigated in 777 people aged 20 years and older (390 men and 387 women). Subjects were asked to complete a postal questionnaire concerning past diet and lifestyle. The completed questionnaires were collected when they had health examinations. The 15 questions included their preference for sweets, how many between-meal snacks they usually had per day, smoking and drinking habits, presence of oral symptoms, and attitudes towards dental visits. Participants were asked about their behaviors at different stages of their life. The oral health examinations included examination of the oral cavity and teeth performed by dentists using WHO criteria. Odds ratios were calculated for all subjects, all 10 year age groups, and for subjects 30 years or older, 40 years or older, 50 years or older, and 60 years or older. RESULTS: Frequency of tooth brushing (OR = 3.98), having your own toothbrush (OR = 2.11), smoking (OR = 2.71) and bleeding gums (OR = 2.03) were significantly associated with number of retained teeth in males. Frequency of between-meal snacks was strongly associated with number of retained teeth in females (OR = 4.67). Having some hobbies (OR = 2.97), having a family dentist (OR = 2.34) and consulting a dentist as soon as symptoms occurred (OR = 1.74) were significantly associated with number of retained teeth in females. Factors that were significantly associated with tooth loss in both males and females included alcohol consumption (OR = 11.96, males, OR = 3.83, females), swollen gums (OR = 1.93, males, OR = 3.04, females) and toothache (OR = 3.39, males, OR = 3.52, females). CONCLUSION: Behavioral factors that were associated with tooth retention were frequency of eating snacks between meals, tooth brushing frequency, having one's own toothbrush, smoking and drinking habits, having hobbies, having a family dentist and when they had dental treatment. Clinical factors included bleeding gums, swollen gums, and toothache

Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization

Kato, K., Satouh, Y., Nishimasu, H. et al. Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization. Nat Commun 7, 12198 (2016). https://doi.org/10.1038/ncomms1219