Dendritic gates for signal integration with excitability-dependent responsiveness.

The shape and excitability of neuronal dendrites are expected to be responsible for the functional characteristics of information processing in the brain. In the present study, we proposed that excitable media with branching patterns mimicked the multi-signal integration of neuronal computation. We initially examined the conditions of the coincidence detection of two inputs as the simplest form of signal integration. We considered a gate with two channels that was bound by a circular joint with uniform excitability and demonstrated that the time window for the coincidence detection was controlled by the geometry and excitability of the gate. The functions of the gate were due to the unique property of the excitation waves, known as the curvature effect. The expanded spatial spread diluted the incoming excitation signals to insufficient levels to sustain wave advancement. Next, we applied dendritic gates that were reminiscent of neuronal dendrites for multi-signal integration. The irregular dendritic patterns were produced by a cellular automaton model of self-organizing pattern formation that adopted the semi-random grid in numerical simulations. We demonstrated that the threshold operation for multiple inputs was conducted by the dendritic pattern. The thresholds varied among gates owing to their irregular patterns, and were adjusted by changing the excitability without changing the gate geometry. The materializable model may provide a novel biomimetic approach for developing fuzzy hardware with adjustable responsiveness

Development and practice of laboratory seismic experiment course and teaching material for understanding realistic seismic refraction survey

地球科学の現象の中でも大気海洋物理や火山分野に比べて、地震学で扱うものは視認しにくく、断層破壊や波動伝播に関する動的な実験教材は殆ど存在しない。地震の源たる断層も教科書では静的なイメージで語られがちである。我々は、実際に見て触って実感できる教材や実習が必要と考え、動的な現象としての地震像をわかりやすく伝えるための実験演習教材を開発する研究に着手した。ここでは、屈折法地震探査によって地下構造を推定する方法とその重要性について学習するための実験演習教材を紹介する。具体的には、寒天模擬地殻に力や振動を与え、波（S波）が伝播する様子を高速カメラで撮影した画像のスロー再生を実際に目で見ることで、実感をともなう理解を促しながら原理を学習する内容となっている。これまで実施した高校生向けの実習や一般公開等での展示などの実用例、およびその教育的効果について報告する。物理探査学会第132回(平成27年度春季)学術講演会（平成27年5月11日～13日, 早稲田大学西早稲田キャンパス

Working report of the combined exercise program for geological and seismological surveys

海洋研究開発機構では高校を始めとする教育機関向けに地質学実習であるSand for Students(S4S)を2005年より実施してきた。一方で、近年推進している地震発生帯研究の成果についても教育機関や中高生向けにわかりやすく伝える機会や方法について模索してきた。そして、新たに地震探査実習を考案し（桑野他、本大会地殻構造セッションにてポスター発表）、今年度S4Sとともに実施することとした。本実習は、（独）科学技術振興機構が理科教育を推進するために運営しているサイエンス・パートナーシップ・プログラムの採択校である横浜高等学校向けに実施したものである。本発表では実際の実習内容とともにその教育的効果、および課題や今後の計画についても紹介する。 　実習プログラムは7月29日（月）?8月2日（金）に実施した。それぞれ２日間の地震学実習と地質学実習を経て、最終日に生徒のとりまとめたプレゼンテーション発表までの全５日間構成となっている。地震学実習では、１日目に屈折法地震探査の実験および実習を行い、２日目に「日本列島の形成」および「海洋プレート沈み込みに伴う海溝型地震研究」をテーマとした特別セミナー、様々な海洋調査機器の見学、実際に研究で使用されている地震計の原理を紹介し、地震計や海底地震計に触れてみる体験を盛り込んだ内容とした。地質学実習は、１日目に酒匂川（丹沢）周辺で地層の観察と鉱物の採取を行い、２日目に採取した鉱物を顕微鏡で観察する内容である。 　地震探査実習では、通常、地面に震動を与えることによって生じる地下を伝わる波を地震計で計測し、記録した後、研究室などに持ち帰りデータ処理、解析をすることが一般的であり、実際の研究で実施している作業プロセスと同じ内容を行うことが多い。今回の地震探査実習では、地震波計測により地下構造が明らかにできることを直感的に理解しやすくすることをねらいとし、地殻を模した寒天２層構造を用いた実験を考えた。この実験では模擬地殻物質が透明であるため光弾性を利用することで、弾性波の伝わる様子を可視化できる。さらに寒天の横波の伝播速度は数m/sと充分遅いため観察が容易になる。この実習では、地震波が伝わる様子をその場で一目で容易に観察でき、さらに観察の様子を録画し、そのデータを画像処理することで寒天模擬地殻表面の各点での振動波形を得ることもできる。この波形データは実際の屈折法地震探査データと同様に解析できるので、これを用いて寒天２層構造の速度構造を推定する演習を行う。演習を行いながら、地震探査を実施して地殻構造を推定することが、地震の発生メカニズムの解明にとって重要であることについて理解を促す。 　地質学実習では、身近な河川の砂を採取して観察することで河川流域の地質を把握するとともに、河川流域の地質の成り立ちを学ぶことで、日本列島形成の重要なメカニズムである付加体形成についての理解を促している。これは同時に、河川を通じて深海底に運ばれる陸源物質を探す作業でもあり、いわば地殻を構成する物質循環の基礎調査に相当する。 　本実習全体のねらいは、地震および地質調査研究に関する基礎的な科学知識・技能を普及させることである。特に、地震国である日本の地で生活する上で、身につけておいてほしい知識や技能の向上、問題の認識を目的としている。今回の実習では、講義、実験、演習、地質巡検を通じて、日本列島の形成や地震研究には地質学、地震学ともに必要であること、さらには様々な学問分野の知識が地球科学にとって重要であることを実感できるような構成とした。今回2日間で実施した地震学実習全体については、今後も実習プログラムの内容の改良、発展を加える上、地震探査実習については、実験レシピを作成して公開することも目指す。P1-36ポスター要旨, 日本地震学会2013年度秋季大会（2013年10月7日～9日, 神奈川県横浜市

The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl.

Papillary thyroid cancer (PTC) among individuals exposed to radioactive iodine in their childhood or adolescence is a major internationally recognized health consequence of the Chernobyl accident. To identify genetic determinants affecting individual susceptibility to radiation-related PTC, we conducted a genome-wide association study employing Belarusian patients with PTC aged 0-18 years at the time of accident and age-matched Belarusian control subjects. Two series of genome scans were performed using independent sample sets, and association with radiation-related PTC was evaluated. Meta-analysis by the Mantel-Haenszel method combining the two studies identified four SNPs at chromosome 9q22.33 showing significant associations with the disease (Mantel-Haenszel P: mhp = 1.7 x 10(-9) to 4.9 x 10(-9)). The association was further reinforced by a validation analysis using one of these SNP markers, rs965513, with a new set of samples (overall mhp = 4.8 x 10(-12), OR = 1.65, 95% CI: 1.43-1.91). Rs965513 is located 57-kb upstream to FOXE1, a thyroid-specific transcription factor with pivotal roles in thyroid morphogenesis and was recently reported as the strongest genetic risk marker of sporadic PTC in European populations. Of interest, no association was obtained between radiation-related PTC and rs944289 (mhp = 0.17) at 14p13.3 which showed the second strongest association with sporadic PTC in Europeans. These results show that the complex pathway underlying the pathogenesis may be partly shared by the two etiological forms of PTC, but their genetic components do not completely overlap each other, suggesting the presence of other unknown etiology-specific genetic determinants in radiation-related PTC

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

Branching pattern formation that reflects the history of signal propagation

In living organisms, branching structures are often observed in open systems. During the process of structure formation/deformation, signal propagation can be observed. Branching paths often deform depending on the history of signal propagation. To gain a better understanding of the process of pattern formation that results in characteristic geometrical paths, we adopt a system in which the dynamics of path formation are correlated with signal propagation. This model involves both branch-generation dynamics and signal-propagation dynamics, and we introduced positive feedback between these two dynamic processes. We studied the geometrical properties of path deformation and the pattern of signal propagation using a discretized reaction-diffusion model. The proposed model can qualitatively reproduce different branching patterns and means of signal propagation. One remarkable result is that the mutual interaction of these two dynamic processes leads to autonomous wave generation, similar to a pacemaker or the generation of spiral waves. Because the autonomous wave generation in the signal is spontaneous, the shapes of the branching paths become distorted. We discuss the correlation between path deformation and signal propagation as a first step in understanding signal processing for such complex deformable paths