Delta-like 1 homolog (DLK1) as a possible therapeutic target and its application to radioimmunotherapy using 125I-labelled anti-DLK1 antibody in lung cancer models (HOT1801 and FIGHT004)

博士（医学）福島県立医科大

Identification and quantification of farmed red sea bream escapees from a large aquaculture area in Japan using microsatellite DNA markers

A large number of farmed red sea bream (Pagrus major) and their gametes have escaped and dispersed into the wild from net-cage aquaculture since the advent of the technology in the mid-20th century. These escapees have likely been recruited into wild populations, affecting their genetic diversity. In this study, we used assignment methods with microsatellite markers to assess the frequency of escapee farmed red sea bream within the wild populations in a major aquaculture production region (UWJ) and in two regions with relatively lower production (IWG and SIJ) in Ehime Prefecture, Japan. The frequency of escapees in UWJ ranged from 14.1% to 30.2%, as shown by three methods of assignment. Escapees were frequently identified among specimens caught by angling (ranging from 26.7% to 46.7%), suggesting that they stay in the same area even after escape or are less cautious than wild individuals. No escapee was found in IWG and SIJ, areas with less extensive aquaculture. Some wild-caught fish appeared to have hybridized with farmed fish, as indicated by the threshold of membership coefficients obtained by simulation. These results clearly indicate that large numbers of farmed individuals have escaped from UWJ, a major aquaculture area, since the inception of red sea bream farming in Japan. Genetic reshuffle has possibly occurred following hybridization of wild and farmed individuals

Structure and Ionic Diffusion in Molten NaI, RbI, and NaI-RbI mixture

Static structure factors of molten NaI, RbI, and their mixture of (RbI)0.3(NaI)0.7 are measured up to high-Q region by using the high-energy Xray diffraction technique. Moreover, molecular dynamics (MD) simulations are carried out, and the simulation results well reproduce the diffraction data. The partial structure factors, partial pair distribution functions, and ionic diffusion coefficients calculated by the MD simulations are reported in detail. The mixing effects of cations on the structure and ionic diffusion are also discussed

Cricotracheostomy for patients with severe COVID-19: A case control study

BackgroundTracheostomy is an important procedure for the treatment of severe coronavirus disease-2019 (COVID-19). Older age and obesity have been reported to be associated with the risk of severe COVID-19 and prolonged intubation, and anticoagulants are often administered in patients with severe COVID-19; these factors are also related to a higher risk of tracheostomy. Cricotracheostomy, a modified procedure for opening the airway through intentional partial cricoid cartilage resection, was recently reported to be useful in cases with low-lying larynx, obesity, stiff neck, and bleeding tendency. Here, we investigated the usefulness and safety of cricotracheostomy for severe COVID-19 patients.Materials and methodsFifteen patients with severe COVID-19 who underwent cricotracheostomy between January 2021 and April 2022 with a follow-up period of ≥ 14 days were included in this study. Forty patients with respiratory failure not related to COVID-19 who underwent traditional tracheostomy between January 2015 and April 2022 comprised the control group. Data were collected from medical records and comprised age, sex, body mass index, interval from intubation to tracheostomy, use of anticoagulants, complications of tracheostomy, and decannulation.ResultsAge, sex, and days from intubation to tracheostomy were not significantly different between the COVID-19/cricotracheostomy and control/traditional tracheostomy groups. Body mass index was significantly higher in the COVID-19 group than that in the control group (P = 0.02). The rate of use of anticoagulants was significantly higher in the COVID-19 group compared with the control group (P < 0.01). Peri-operative bleeding, subcutaneous emphysema, and stomal infection rates were not different between the groups, while stomal granulation was significantly less in the COVID-19 group (P = 0.04).ConclusionsThese results suggest that cricotracheostomy is a safe procedure in patients with severe COVID-19

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

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

Identification and quantification of farmed red sea bream escapees from a large aquaculture area in Japan using microsatellite DNA markers

A large number of farmed red sea bream (Pagrus major) and their gametes have escaped and dispersed into the wild from net-cage aquaculture since the advent of the technology in the mid-20th century. These escapees have likely been recruited into wild populations, affecting their genetic diversity. In this study, we used assignment methods with microsatellite markers to assess the frequency of escapee farmed red sea bream within the wild populations in a major aquaculture production region (UWJ) and in two regions with relatively lower production (IWG and SIJ) in Ehime Prefecture, Japan. The frequency of escapees in UWJ ranged from 14.1% to 30.2%, as shown by three methods of assignment. Escapees were frequently identified among specimens caught by angling (ranging from 26.7% to 46.7%), suggesting that they stay in the same area even after escape or are less cautious than wild individuals. No escapee was found in IWG and SIJ, areas with less extensive aquaculture. Some wild-caught fish appeared to have hybridized with farmed fish, as indicated by the threshold of membership coefficients obtained by simulation. These results clearly indicate that large numbers of farmed individuals have escaped from UWJ, a major aquaculture area, since the inception of red sea bream farming in Japan. Genetic reshuffle has possibly occurred following hybridization of wild and farmed individuals