Oxidative etching mechanism of the diamond (100) surface

John Isaac Enriquez, Fahdzi Muttaqien, Masato Michiuchi, Kouji Inagaki, Masaaki Geshi, Ikutaro Hamada, Yoshitada Morikawa, Oxidative etching mechanism of the diamond (100) surface, Carbon, Volume 174, 2021, Pages 36-51, https://doi.org/10.1016/j.carbon.2020.11.057

Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several relaxing factors, such as prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have previously demonstrated in animals and humans that endothelium-derived hydrogen peroxide (H2O2) is an EDHF that is produced in part by endothelial NO synthase (eNOS). In this study, we show that genetic disruption of all three NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]) abolishes EDHF responses in mice. The contribution of the NOS system to EDHF-mediated responses was examined in eNOS−/−, n/eNOS−/−, and n/i/eNOS−/− mice. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine of mesenteric arteries were progressively reduced as the number of disrupted NOS genes increased, whereas vascular smooth muscle function was preserved. Loss of eNOS expression alone was compensated for by other NOS genes, and endothelial cell production of H2O2 and EDHF-mediated responses were completely absent in n/i/eNOS−/− mice, even after antihypertensive treatment with hydralazine. NOS uncoupling was not involved, as modulation of tetrahydrobiopterin (BH4) synthesis had no effect on EDHF-mediated relaxation, and the BH4/dihydrobiopterin (BH2) ratio was comparable in mesenteric arteries and the aorta. These results provide the first evidence that EDHF-mediated responses are dependent on the NOSs system in mouse mesenteric arteries

TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling

The mammalian target of rapamycin (mTOR) pathway is commonly activated in human cancers. The activity of mTOR complex 1 (mTORC1) signaling is supported by the intracellular positioning of cellular compartments and vesicle trafficking, regulated by Rab GTPases. Here we showed that tuftelin 1 (TUFT1) was involved in the activation of mTORC1 through modulating the Rab GTPase-regulated process. TUFT1 promoted tumor growth and metastasis. Consistently, the expression of TUFT1 correlated with poor prognosis in lung, breast and gastric cancers. Mechanistically, TUFT1 physically interacted with RABGAP1, thereby modulating intracellular lysosomal positioning and vesicular trafficking, and promoted mTORC1 signaling. In addition, expression of TUFT1 predicted sensitivity to perifosine, an alkylphospholipid that alters the composition of lipid rafts. Perifosine treatment altered the positioning and trafficking of cellular compartments to inhibit mTORC1. Our observations indicate that TUFT1 is a key regulator of the mTORC1 pathway and suggest that it is a promising therapeutic target or a biomarker for tumor progression.UTokyo FOCUS Articles掲載「がんの増殖・転移を促進する新規因子の同定 小胞輸送を標的とする新しいがん治療戦略への可能性」 https://www.u-tokyo.ac.jp/focus/ja/articles/z0508_00119.htmlUTokyo FOCUS Articles "Possible target for future cancer treatment : Deregulation of system to move molecules in the cell may promote tumor growth, metastasis" https://www.u-tokyo.ac.jp/focus/en/articles/z0508_00120.htm

Detection of viral RNA in diverse body fluids in an SFTS patient with encephalopathy, gastrointestinal bleeding and pneumonia: a case report and literature review

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established. CASE PRESENTATION: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted. CONCLUSIONS: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed

Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero

Newly identified tissue-resident vascular precursor cells are recruited into growing vessels and contribute to vasculogenesis in adult mice

コウレイシャ テンカン ノ モンシンヒョウ ニヨル ソウキ ハッケン : ニンチショウ トノ カンレン ニオイテ

本研究の目的は高齢者てんかんを問診票の活用により、物忘れ外来を含む高齢者複合施設における高齢者てんかんの実態を明らかにすることにある。物忘れ外来を含む高齢者複合施設を調査期間中に利用した417名を対象に、高齢者てんかん問診票を用い、てんかん有病率を算出した。また、新規に高齢者てんかんと判定された者の特徴を記述した。その結果、すでにてんかんの診断ありが7名（1.7%）、問診票の回答内容からてんかんの疑いありは33名（7.9%）、その中から医師の診断により新規に高齢者てんかんが判定された者は14名（3.0%）であった。施設別有病率では、物忘れ外来7名（5.0%）、ショートステイ利用者、グループホーム入所者は2割前後であった。新規に高齢者てんかんと判定された者の問診項目では、意識減損がもっとも多かった。さらに、新規にてんかんが判明したすべての者が何らかの認知症を有していた。本研究により物忘れ外来を含む高齢者複合施設において、高齢者てんかんが潜在していることが明らかとなり、これらの早期発見のため高齢者てんかんの問診票の必要性が示された

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

無治療経過観察した腎腫瘍の自然経過

With the widespread use of imaging modalities, incidentally discovered small renal cell carcinomas have increased. Some patients, however, are too old or weak due to various diseases to undergo surgery and other patients occasionally refuse surgery. To investigate the natural history of small renal cell carcinoma, we retrospectively reviewed patients with small renal tumors suggestive of carcinoma. We retrospectively reviewed 15 patients with contrast-enhancing renal masses less than 4.0 cm in diameter who were observed without treatment. The mean follow-up period was 38 months (range, 8-91). The average patient age was 67 years (range, 44-87). The initial average tumor diameter was 2.2 cm (range, 1.0-3.9). The average growth rate was 0.06 cm per year (range, -0.09-0.28). Only 4 tumors grew obviously during the follow-up period. Three tumors were removed surgically by radical nephrectomy, and all tumors were pathologically diagnosed as renal cell carcinoma. None of the patients developed metastases during the follow-up period or after surgery. Two patients died of other causes. Nonsurgical watchful waiting may be an acceptable treatment option for elderly or severely comorbid patients; however, it is not known whether this conservative management can be applied to young or otherwise healthy patients.検診や他疾患の精査で画像検査を受ける機会が増加してきたのに伴い, 偶然発見される小さな腎癌が増加してきている。画像上腎癌が疑われる場合, 通常すぐに外科的に摘除されるが, 高齢者や重篤な合併症を有する患者では手術をためらうことがある。また患者が手術を拒否する場合もある。腎癌の自然経過はよくわかっていない。われわれは画像検査で腎癌が疑われながら無治療で経過観察した, 15例について検討した。CT検査上, 造影剤で造影される4cm以下の腫瘍を対象とした。腫瘍発見時の平均年齢は67歳, 平均腫瘍径は22mm, 平均観察期間は38ヵ月だった。腫瘍の平均増大速度は1年当たり0.06cmで, 経過中腫瘍径が明らかに増大したのは4例のみだった。経過中3例外科的に摘除し, すべて腎癌と診断された。無治療経過観察中あるいは術後に転移が出現した症例はなかった。無治療経過観察した2例が他病死した。悪性が疑われる小さな腎腫瘍を認めても, 高齢者や重篤な合併症を有する患者では, 経過観察も選択肢の1つになりうると考えられた。しかし, 若い患者や状態のよい患者に適応できるかは慎重に検討する必要がある。(著者抄録