哺乳類の減数分裂期に染色体末端"テロメア"に形成される新規タンパク質複合体の同定と機能解析

学位の種別:課程博士University of Tokyo(東京大学

Essential role of the Cdk2 activator RingoA in meiotic telomere tethering to the nuclear envelope

Cyclin-dependent kinases (CDKs) play key roles in cell cycle regulation. Genetic analysis in mice has revealed an essential role for Cdk2 in meiosis, which renders Cdk2 knockout (KO) mice sterile. Here we show that mice deficient in RingoA, an atypical activator of Cdk1 and Cdk2 that has no amino acid sequence homology to cyclins, are sterile and display meiotic defects virtually identical to those observed in Cdk2 KO mice including non-homologous chromosome pairing, unrepaired double-strand breaks, undetectable sex-body and pachytene arrest. Interestingly, RingoA is required for Cdk2 targeting to telomeres and RingoA KO spermatocytes display severely affected telomere tethering as well as impaired distribution of Sun1, a protein essential for the attachment of telomeres to the nuclear envelope. Our results identify RingoA as an important activator of Cdk2 at meiotic telomeres, and provide genetic evidence for a physiological function of mammalian Cdk2 that is not dependent on cyclins

Characteristics of Inattention and Hyperactivity, Perception of General Health, and Reading Literacy of Japanese Adolescents: Results from a Large-scale Community Sample

Adolescents with reading literacy difficulty with comorbid attention deficit hyperactivity disorder are often at a greater risk for problems of communication, and behavioral and mental health challenges. We aimed to examine literacy weakness for the native Japanese language of KOKUGO and the foreign language of ENGLISH as perceived by Japanese adolescents. We also aimed to analyze the relationship between literacy weakness and inattention and hyperactivity characteristics. We conducted a largescale questionnaire survey of 2987 junior high school students. We used logistic regression analysis to examine the data fromthe self-report Strengths and Difficulties Questionnaire (SDQ), the General Health Questionnaire-12, and adolescents’ perceptions of their command of KOKUGO and ENGLISH. We found a significant association between perceived literacy for both languagesand SDQ inattention and hyperactivity characteristics. Reading difficulties in ENGLISH may be addressed by introducing ENGLISH at an earlier age supported by clinically enhanced pedagogy

Does physiotherapy after rotator cuff repair require supervision by a physical therapist?: a meta-analysis

Background A supervised physiotherapy program (SPP) is a standard regimen after surgical rotator cuff repair (RCR); however, the effect of a home-based exercise program (HEP), as an alternative, on postoperative functional recovery remains unclear. Therefore, the purpose of this meta-analysis was to compare the functional effects of SPP and HEP after RCR. Methods We searched electronic databases including Central, Medline, and Embase in April 2022. The primary outcomes included the Constant score, American Shoulder and Elbow Surgeons score, University of California Los Angeles shoulder score, and pain score. Secondary outcomes included range of motion, muscle strength, retear rate, and patient satisfaction rate. A meta-analysis using random-effects models was performed on the pooled results to determine the significance. Results The initial database search yielded 848 records, five of which met our criteria. Variables at 3 months after surgery were successfully analyzed, including the Constant score (mean difference, −8.51 points; 95% confidence interval [CI], −32.72 to 15.69; P=0.49) and pain score (mean difference, 0.02 cm; 95% CI, −2.29 to 2.33; P=0.99). There were no significant differences between the SPP and HEP. Other variables were not analyzed owing to the lack of data. Conclusions Our data showed no significant differences between SSP and HEP with regard to the Constant and pain scores at 3 months after RCR. These results suggest that HEP may be an alternative regimen after RCR. Level of evidenceI

トウカガタ ジシンケイ (ペネトレータ) ノ ナンキョク ミズホ コウゲン デノ シケン カンソク ダイ43ジ ナツタイ ホウコク

南極氷床上のクレバス帯等の,地上からは到達困難な地域での人工地震観測を目的とした投下型地震観測装置(南極ペネトレータ)を開発し,第43次日本南極地域観測隊で実施する東南極みずほ高原における人工地震探査で使用するために,22本のペネトレータを昭和基地に持ち込んだ.しかし,開発の遅れに伴う国内試験の不足から種々の不具合が発生し,今回は本観測での使用をあきらめざるを得なかった.当初の目的は果たすことができなかったが,国内では得られない環境でのペネトレータ投下実験を行い,投下姿勢,着地衝撃力,温度変化等の貴重なデータを得るとともに,南極内陸部での実際のヘリコプター運用への知見を得ることができた.これらの成果はペネトレータ型地震計の改良のみならず,今後の各種投下型観測機器の開発・製作に多いに役に立つものと考えられる.We have developed an Antarctic penetrator that is applicable to seismic explosion experiments along a difficult traverse route on a continental ice sheet with crevasses. In the 43rd Japanese Antarctic Research Expedition (JARE-43, 2001-2002) seismic explosion experiments on the Mizuho Plateau, in East Antarctica, we equipped 22 penetrators for seismic observation. However, due to electrical trouble, we could not apply the penetrators to actual observation. Then, we carried out a running test of the penetrators and acquired much valuable data that cannot be obtained in the domestic environment in Japan, such as the declination angle of a body intruding into the Antarctic ice sheet, impact shock, and daily change of temperature of the body in the snow. These data are not only useful for development of the Antarctic penetrator, but also for development of touchdown-type physical observation equipment for use in Antarctica

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS

The efficacy of polyglycolic acid felt reinforcement in preventing postoperative pancreatic fistula after pancreaticojejunostomy in patients with main pancreatic duct less than 3 mm in diameter and soft pancreas undergoing pancreatoduodenectomy (PLANET-PJ trial): study protocol for a multicentre randomized phase III trial in Japan and Korea

Background Partial pancreatoduodenectomy is performed for malignant and benign diseases of the pancreatic head region. The procedure is considered highly difficult and highly invasive. Postoperative pancreatic fistula (POPF) is an important complication because of several consequent complications, including intraabdominal haemorrhage, often increasing hospital stays and surgical mortality. Although many kinds of pancreaticojejunostomy aimed at reducing POPF have been examined to date, the technique has not yet been standardized. We devised a new method using double-coated polyglycolic acid felt after pancreaticojejunostomy. The aim of the PLANET-PJ trial is to evaluate the superiority of polyglycolic acid felt reinforcement in preventing POPF after pancreaticojejunostomy in patients undergoing partial pancreatoduodenectomy to previous anastomosis methods. Methods Patients diagnosed with pancreatic or periampullary lesions in whom it is judged that the main pancreatic duct diameter was 3 mm or less on the left side of the portal vein without pancreatic parenchymal atrophy due to obstructive pancreatitis are considered eligible for inclusion. This study is designed as a multicentre randomized phase III trial in Japan and the Republic of Korea. Eligible patients will be centrally randomized to either group A (polyglycolic acid felt reinforcement) or group B (control). In total, 514 patients will be randomized in 31 high-volume centres in Japan and Republic of Korea. The primary endpoint is the incidence of POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion The PLANET-PJ trial evaluates the efficacy of a new method using double-coated polyglycolic acid felt reinforcement for preventing POPF after pancreaticojejunostomy. This new method may reduce POPF. Trial registration ClinicalTrials.gov, NCT03331718 . University Hospital Medical Information Network Clinical Trials Registry, UMIN000029647. Registered on 30 November 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000033874This study is funded by GUNZE LIMITED, based on the contract. The status of conflicts of interest of the principle investigator is examined by the Conflicts of Interest Management Committee of University of Toyama, prior to the ethical review by the IRB

Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive motoneuron loss. Redistribution of transactive response deoxyribonucleic acid-binding protein 43 from the nucleus to the cytoplasm and the presence of cystatin C-positive Bunina bodies are considered pathological hallmarks of amyotrophic lateral sclerosis, but their significance has not been fully elucidated. Since all reported rodent transgenic models using wild-type transactive response deoxyribonucleic acid-binding protein 43 failed to recapitulate these features, we expected a species difference and aimed to make a non-human primate model of amyotrophic lateral sclerosis. We overexpressed wild-type human transactive response deoxyribonucleic acid-binding protein 43 in spinal cords of cynomolgus monkeys and rats by injecting adeno-associated virus vector into the cervical cord, and examined the phenotype using behavioural, electrophysiological, neuropathological and biochemical analyses. These monkeys developed progressive motor weakness and muscle atrophy with fasciculation in distal hand muscles first. They also showed regional cytoplasmic transactive response deoxyribonucleic acid-binding protein 43 mislocalization with loss of nuclear transactive response deoxyribonucleic acid-binding protein 43 staining in the lateral nuclear group of spinal cord innervating distal hand muscles and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with amyotrophic lateral sclerosis. Transactive response deoxyribonucleic acid-binding protein 43 mislocalization was an early or presymptomatic event and was later associated with neuron loss. These findings suggest that the transactive response deoxyribonucleic acid-binding protein 43 mislocalization leads to α-motoneuron degeneration. Furthermore, truncation of transactive response deoxyribonucleic acid-binding protein 43 was not a prerequisite for motoneuronal degeneration, and phosphorylation of transactive response deoxyribonucleic acid-binding protein 43 occurred after degeneration had begun. In contrast, similarly prepared rat models expressed transactive response deoxyribonucleic acid-binding protein 43 only in the nucleus of motoneurons. There is thus a species difference in transactive response deoxyribonucleic acid-binding protein 43 pathology, and our monkey model recapitulates amyotrophic lateral sclerosis pathology to a greater extent than rodent models, providing a valuable tool for studying the pathogenesis of sporadic amyotrophic lateral sclerosis