アラカワジョウリュウ ノ レキシュ ト チチブチホウ ノ チシツ ノ カンケイセイ ─セキザイキョウイク ノ キョウザイ ノ テイアン─

本研究は，関東地方有数の石材産地である秩父地方において，荒川上流の河原の礫種がどのように秩父地方の地質を反映しているかを把握することで，造園石材や建築石材の教材を提案することを目的とした。公共交通機関からアクセスでき，河原に降りて調査を実行可能な場所，かつ荒川の流路が湾曲し，礫が多く堆積している場所から6地点を選定した。それぞれ5mのひもを3回のばし，ひもに触れた長径5～20cmの礫を対象とした。「地質図Navi」から秩父地方の岩石の分布域を抽出し，石材に多用される岩石の種類をもとに3回調査した結果，6地点はいずれも砂岩類（緑色岩類を含む）・泥岩類が上位を占めており，花崗岩類・チャート・石灰岩・蛇紋岩・緑泥石片岩およびその他の結晶片岩類が認められた。6地点の礫種の変化は，支流上流の地質にも大きく影響されていると考えられる。また，人工護岸の有無や，礫の大きさや形状を左右する岩石自体の性質も，礫種の変化に影響を与えていると推察される。以上の6地点は石材教育の教材として，造園石材や建築石材に対する理解の向上，地域の石材と地質の関係性に対する理解の向上，調査スケジュールの高い自由度が期待できる。The Chichibu region is one of the important stone-producing areas in the Kanto region. We aimed to propose teaching materials for the education of gardening stone and building stone, by understanding how the gravel species on the riverbed of the Arakawa River reflect the geology of the Chichibu region. We selected 6 sites on curved riverbed where public transportation is available, and where the Arakawa River is curved. On each site, a string of 5 m was pulled in 3 places and the gravel with a major axis of 5 to 20 cm that touched the string were recorded. After extracting the geological information from GeoNavi (GSJ/AIST), the investigation was conducted 3 times. As a result, sandstone (including greenstone) and mudstone occupied the top-level in 6 sites. Granite, chert, limestone, serpentinite, greenschist, and other crystalline schist were confirmed. It is considered that the changes in gravel species at the 6 sites are also affected by the upstream geology of the tributaries. In addition, the artificial revetments and the hardness of the rock also possibly affect the change of gravel species. The 6 sites can be scheduled conveniently, as teaching materials for the education of gardening stones and building stones, as well as the understanding of the relationship between the material regionality and geology

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

Hyperfibrinolysis in severe isolated traumatic brain injury may occur without tissue hypoperfusion : a retrospective observational multicentre study

Background: Hyperfibrinolysis is a critical complication in severe trauma. Hyperfibrinolysis is traditionally diagnosed via elevated D-dimer or fibrin/fibrinogen degradation product levels, and recently, using thromboelastometry. Although hyperfibrinolysis is observed in patients with severe isolated traumatic brain injury (TBI) on arrival at the emergency department (ED), it is unclear which factors induce hyperfibrinolysis. The present study aimed to investigate the factors associated with hyperfibrinolysis in patients with isolated severe TBI. Methods: We conducted a multicentre retrospective review of data for adult trauma patients with an injury severity score >= 16, and selected patients with isolated TBI (TBI group) and extra-cranial trauma (non-TBI group). The TBI group included patients with an abbreviated injury score (AIS) for the head >= 4 and an extra-cranial AIS = 3 and head AIS = 38 mg/L on arrival at the ED. We evaluated the relationships between hyperfibrinolysis and injury severity/tissue injury/tissue perfusion in TBI patients by comparing them with non-TBI patients. Results: We enrolled 111 patients in the TBI group and 126 in the non-TBI group. In both groups, patients with hyperfibrinolysis had more severe injuries and received transfusion more frequently than patients without hyperfibrinolysis. Tissue injury, evaluated on the basis of lactate dehydrogenase and creatine kinase levels, was associated with hyperfibrinolysis in both groups. Among patients with TBI, the mortality rate was higher in those with hyperfibrinolysis than in those without hyperfibrinolysis. Tissue hypoperfusion, evaluated on the basis of lactate level, was associated with hyperfibrinolysis in only the non-TBI group. Although the increase in lactate level was correlated with the deterioration of coagulofibrinolytic variables (prolonged prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels, and increased D-dimer levels) in the non-TBI group, no such correlation was observed in the TBI group. Conclusions: Hyperfibrinolysis is associated with tissue injury and trauma severity in TBI and non-TBI patients. However, tissue hypoperfusion is associated with hyperfibrinolysis in non-TBI patients, but not in TBI patients. Tissue hypoperfusion may not be a prerequisite for the occurrence of hyperfibrinolysis in patients with isolated TBI

High D-dimer levels predict a poor outcome in patients with severe trauma, even with high fibrinogen levels on arrival : a multicenter retrospective study

Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicentre retrospective study. This study included 519 adult trauma patients with an injury severity score ≥16. Patients with ≥10 units of red cell concentrate transfusion and/or death during the first 24 hours were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D-dimer values to be 190 mg/dL and 38 mg/L, respectively. Based on these values, patients were divided into four groups: (1) low D-dimer (190 mg/dL), (2) low D-dimer (190 mg/dL), and (4) high D-dimer (≥38 mg/L)/low fibrinogen (≤190 mg/dL). The survival rate was lower in the high D-dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels