In Orbit Timing Calibration of the Hard X-Ray Detector on Board Suzaku

The hard X-ray detector (HXD) on board the X-ray satellite Suzaku is designed to have a good timing capability with a 61 $\mu$s time resolution. In addition to detailed descriptions of the HXD timing system, results of in-orbit timing calibration and performance of the HXD are summarized. The relative accuracy of time measurements of the HXD event was confirmed to have an accuracy of $1.9\times 10^{-9}$ s s$^{-1}$ per day, and the absolute timing was confirmed to be accurate to 360 $\mu$s or better. The results were achieved mainly through observations of the Crab pulsar, including simultaneous ones with RXTE, INTEGRAL, and Swift.Comment: Accepted for publication on PASJ Vol.60, SP-1, 200

Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group

The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR\u27ABL-negative ALL. Patients aged 15\u2724 years (n = 139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58\u2775%) and 73% (95% CI 64\u2780%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, Po0.001).These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR\u27ABL-negative ALL

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

カキの発芽期以降における花器の発育について(農学部門)

カキ平核無の成木を用い, 発芽期より開花時までの花器(雌花)の発育過程を明らかにするため, 1973年4月初旬より組織学的な調査を行なった。その結果, 花の各器官はがく片, 花弁, 偽雄ずいおよび心皮の順に外側器官から分化形成された。それぞれの器官の発育をみると, 発芽時ではがく片および花弁の突起が観察されただけで, その他の器官分化は認められなかった。発芽時より5∿7日後には偽雄ずいおよび心皮の突起が分化し, 急速に各器官の発育が進み, 4月中旬には心皮突起の内側基部より胚珠の突起が分化しはじめた。4月下旬には珠心および珠皮が形成され, 珠心内で胚のう母細胞が分化した。その後花器の生長にともない, 開花のほぼ2日前に胚珠が完成した。また雄ずいは葯壁のみが形成され, タペート細胞および花粉は形成されなかった。以上のように, カキの花器は発芽時より各器官が分化し, 新梢の伸長にともない急速にその発育をとげ, 発芽時よりほぼ6週めで花器の形態が完成されることを認めたが, 他の果樹の花芽発育と比較して特異な発育を示した。The development of female floral organ in Japanese persimmon (cv. Hiratanenashi) has been followed from the time of sprouting until full bloom. The obtained results were as follows. The differentiation of each organ was initiated from the outer organs, namely in order of calyx, petal, staminodium, and carpel. Only calyx and petal primordia were observed at sprouting, but staminodium and carpel primordia differentiated about 5 to 7 days after sprouting. The ovule primordia were initiated on the infolded carpel edges near the base of the ovarian cavity in the middle of April, and the growth of them was more rapid. Integument, nucellus and embryo-sac mother cell were formed in the end of April. The formation of ovule was completed about 2 days before full bloom, but no differetiation of tapetum and pollen grains was observed in the staminodium. Thus, the formation floral organ in Japanese persimmon was completed about 6 weeks from the sprouting time