Comparisons in temperature and photoperiodic-dependent diapause induction between domestic and wild mulberry silkworms

The bivoltine strain of the domestic silkworm, Bombyx mori, has two generations per year. It shows a facultative diapause phenotype determined by environmental conditions, including photoperiod and temperature, and nutrient conditions during embryonic and larval development of the mother. However, it remains unclear how the environmental signals received during development are selectively utilized as cues to determine alternative diapause phenotypes. We performed a comparative analysis between the Kosetsu strain of B. mori and a Japanese population of the wild mulberry silkworm B. mandarina concerning the hierarchical molecular mechanisms in diapause induction. Our results showed that for the Kosetsu, temperature signals during the mother's embryonic development predominantly affected diapause determination through the thermosensitive transient receptor potential ankyrin 1 (TRPA1) and diapause hormone (DH) signaling pathways. However, embryonic diapause in B. mandarina was photoperiod-dependent, although the DH signaling pathway and thermal sensitivity of TRPA1 were conserved within both species. Based on these findings, we hypothesize that TRPA1-activated signals are strongly linked to the signaling pathway participating in diapause induction in Kosetsu to selectively utilize the temperature information as the cue because temperature-dependent induction was replaced by photoperiodic induction in the TRPA1 knockout mutant.ArticleScientific Report 11(1) : 8052-(2021)journal articl

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

<臨床>腹腔鏡下胆囊摘出術の合併症を予防するために

Laparoscopic cholecystectomy is now becoming a safe procedure for the benign cholecystic diseases. But the differences, for example in the method of access to peritoneal cavity, visual field, and tools, between laparoscopic surgery and open surgery results in different complications. The purpose of this paper is to discuss how to avoid complications during laparoscopic cholecystectomy. A hundred consecutive patients were expected to receive an elective laparoscopic cholecystectomy from April 1991 to November 1992 in our clinic. Two patients were converted to open cholecystectomy. The reasons for conversion were uncontrollable bleeding from cystic artery and common-bile duct injury. Two other patients were obliged to undergo laparotomy due to postoperative bile leakage. Arterial bleeding from abdominal wall caused by inserting trocar was experienced in one case. Improvement of the equipment and surgical technique have got rid of these complications. We think it is still necessary to do intra-operative examinations such as cholangiography or ultrasonography. The previous two cases with complication of biliary injury underwent laparoscopic cholecystectomy without intraoperative examinations. We could have avoided these complications if intraoperative examinations were used. To prevent the complication of bleeding from abdominal wall, we have been carrying out a unique method. After the introduction of these procedures, we have never experienced any of theses complications.腹腔鏡下胆嚢摘出術は良性胆嚢疾患に対し, 安全な治療法の1つとなりつつある. 開腹胆嚢摘出術と腹腔内操作は基本的に同じであるが, 腹腔鏡下胆嚢摘出術では術中の視野や処置具の違いから術中合併症が生じることがある. 教室でも, 開腹術に移行あるいは術後に再開腹を行った症例を経験している. これら術中合併症を生じた各々の症例につきその原因と予防策を検討し報告したい. 1991年4月から1992年11月までに教室で、腹腔鏡下胆嚢摘出術を受けた100症例のうち, 合併症のため開腹手術に移行した症例は2例, 術後再開腹を受けた症例は2例であった. また, 術中腹壁血管の損傷のため腹腔内に出血した症例を1例経験した. これら5症例は, いずれも初期の40症例までにみられ, 以後の60症例は開腹術移行例, 術後再開腹例, 腹壁血管損傷のいずれもみられていない. 開腹手術に移行した2症例は胆嚢動脈からの出血例と総胆管損傷であった術後再開腹となった2症例は十二指腸損傷と総胆管損傷であった. これらの症例以後, われわれは, ほぼ全例に術中検査として胆道造影と超音波検査を行い胆管の確認を行っている. また, 胆嚢壁の肥厚, 胆嚢管周囲の炎症がみられる症例に対しては CUSA を用いて剥離を行っている. 手術時聞は術中検査を行ったにもかかわらず後期の60症例の方が有意に短く, 手技の習熟も合併症を防ぐうえで重要な要素の1つであった. 以上のことから, 本術式で起り得る合併症を予防するためには, 1)充分な性能を有する器械を用いること, 2)処置具を安全に操作できるように手技を習熟すること, 3)できる限り術中検査を行い確実に胆道の解剖学的位置関係を把握することが重要であると考えられた

Gated carbon-ion scanning treatment for pancreatic tumour with field specific target volume and organs at risk.

Objective To assess the feasibility of treatment planning for pancreatic tumours subject to respiratory motion using field-specific target volumes (FTV) and field-specific organs at risk (FOAR) using four-dimensional computed tomography (4DCT).\n Methods Fourteen pancreatic cancer patients underwent 4DCT. Radiation oncologists contoured the gross tumour volume (GTV), clinical target volume (CTV), spinal cord, duodenum, kidneys, and stomach. The gating duty cycle was set to 30 % around exhalation. FTV and FOAR were calculated using the 4DCT dataset. Planning target volumes (PTV) and planning organs at risk volumes (PRV) were defined as equal to FTV and FOAR, respectively. A dose of 55.2 Gy relative biological effectiveness (RBE) was planned to target the PTV from four beam angles. A single field uniform dose (SFUD) plan was selected. The dose distribution, including intrafractional motion changes, was generated.\n Results The mean volume of target receiving 95 % of the planned doses was 96.4 ± 4.1 % to the GTV and 94.7 ± 0.9 % to the CTV. The highest dose to 2 cc of duodenal volume was 27.5 Gy (RBE). The volume of the stomach receiving ⩾30 Gy (RBE) was <7.0 cc in all patients. All metrics for OARs satisfied dose constraints.\n Conclusion Dose to the CTV was covered sufficiently by the 4DCT-generated FTV, and dose to OARs was reduced by 4DCT-generated FOAR. This methodology may prevent adverse reactions while preserving local tumour control

Carbon-ion Radiotherapy for Hepatocellular Carcinoma

AbstractClinical trials of carbon ion radiotherapy (C-ion RT) for hepatocellular carcinoma (HCC) were conducted at the National Institute of Radiological Sciences (NIRS) in Japan between April 1995 and August 2005. In four clinical studies, we tried to determine the optimal dose and to shorten the treatment duration using five different fractionation schedules comprising 15, 12, eight, four and two fractions. There have been no treatment-related deaths and no severe adverse events. As a result of these studies, the duration of treatment could be reduced from five weeks to two days. Two-fraction therapy is currently ongoing, licensed as a Highly Advanced Medical Technology. Between April 2003 and August 2012, 133 patients with HCC underwent two fraction C-ion RT. There were no cases of grade 4 toxicity. The local control rates were 98% and 83% at one and three years, respectively, with a total dose of 45.0 GyE. Because of the low toxicity and good local control rate, C-ion RT is a promising radical and minimally invasive therapeutic option for HCC