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

Data from: Development of resurgent and persistent sodium currents in mesencephalic trigeminal neurons

Sodium channels play multiple roles in the formation of neural membrane properties in mesencephalic trigeminal (Mes V) neurons and in other neural systems. Mes V neurons exhibit conditional robust high-frequency spike discharges. As previously reported, resurgent and persistent sodium currents (INaR and INaP, respectively) may carry small currents at subthreshold voltages that contribute to generation of spike firing. These currents play an important role in maintaining and allowing high-frequency spike discharge during a burst. In the present study, we investigated the developmental changes in tetrodotoxin-sensitive INaR and INaP underlying high-frequency spike discharges in Mes V neurons. Whole-cell patch-clamp recordings showed that both current densities increased one and a half times from postnatal day 0-6 neurons to postnatal day 7-14 neurons. Although these neurons do not exhibit subthreshold oscillations or burst discharges with high-frequency firing, INaR and INaP do exist in Mes V neurons at postnatal day 0-6. When the spike frequency at rheobase was examined in firing Mes V neurons, the developmental change in firing frequency among P7 to P14 neurons was significant. INaR and INaP density at −40 mV also increased significantly among P7 to P14 neurons. The change to an increase in excitability in the P7-14 group could result from this quantitative change in INaP. In neurons older than P7 that exhibit repetitive firing, quantitative increases in INaR and INaP density may be major factors that facilitate and promote high-frequency firing as a function of age in Mes V neurons

dryad data enomoto

primary data (R and P enomoto

Oral Medicine Update

口腔には，噛む，飲み込む，味わう，話すなどの様々な機能があり，人間にとっての生きるための根源となる機能が備わっており，日常生活と直結した動作や機能の多くが担われています．日本は世界に先駆けて超高齢社会に突入しており，「健康寿命」の延伸は最も重要な課題の一つとされ，「人生100年時代」を迎える私たちにとっては，「生活の質」が重要とされています．「口腔の健康が全身の健康に密接に関わる」ということが近年多く報告され明らかになりつつあり，病気にならない予防，病気以前の不調段階の未病への対応，また老年期に体が弱るフレイルへの対処についても歯や口の健康管理を重点化することが重要であるといわれています．歯科における口腔疾患には代表とされるう蝕と歯周病の2 大疾患のほか，様々な各論があり，それぞれの分野にて多くの研究がなされ，発展してきています．本稿では，口腔医療の歴史からはじめ，現在にいたる口腔医療，将来展望についてまとめました．departmental bulletin pape

〈Originals〉Swallowing function in patients who underwent after subtotal glossectomy and reconstruction with a rectus abdominis musculocutaneous flap

[Abstract]Purpose: Swallowing function was evaluated 3 years after surgery in three tongue cancer patients who underwent bilateral total neck dissection and subtotal glossectomy with reconstruction using a rectus abdominis musculocutaneous flap. Materials and Methods: The morphology of the flap and swallowing function were evaluated. Swallowing function was assessed by video fluorography with a 10 ml test diet. The items for evaluation of swallowing were: (1) holding the test diet in the oral cavity, (2) epiglottis turnover, (3) aspiration, (4) hyoid bone movement, and (5) maximum width of the esophageal entrance. Results: With regard to flap morphology, two patients had a protuberant flap and one had a semi-protuberant flap. One patient was able to hold the test diet in the oral cavity, while slight flow of the test diet into the pharynx was observed in the other 2 patients. Epiglottis turnover was good in one patient, but was insufficient in two patients. Aspiration was not observed in any of the patients. The hyoid bone moved forward and upward in all three patients. The maximum width of the esophageal entrance was good in all patients. Conclusions: Elevation of the hyoid bone was demonstrated in all three patients, even though almost all of the bilateral suprahyoid muscles had been resected with the exception of stylohyoid. For good postoperative swallowing function and hyoid bone movement after subtotal glossectomy, it is necessary to perform reconstruction with a flap that has sufficient volume and to retain the bilateral stylohyoid muscles