Response time differences during hand mental rotation

This study explored gender differences in correct response rates and response times on a task involving left or right arrow selection and another involving the transformation of mental rotation of the hand. We recruited 15 healthy, right-handed men (age 24.5 ± 6.4) and 15 healthy, right-handed women (age 21.3 ± 4.9). For the tasks, we used pictures of left and right arrows and 32 hand pictures (left and right, palm and back) placed in cons (each at 45° from 0° to 315°). Hand and arrow pictures alternated and were shown at random. Participants decided as quickly as possible whether each picture was left or right. To compare the time taken for the transformation of mental rotation of the hand, we subtracted the average arrow response time from that for the left and right hand pictures for each participant. Correct response rates did not differ significantly between men and women or left and right for either arrow or hand pictures. Regardless of gender, the response time was longer for the left arrow picture than right arrow picture. The response time for the hand picture was longest for both men and women for pictures at rotation angles that were most difficult to align with participants’ hands. While there was no difference between men’s responses for left and right hand pictures, the responses of women were longer for left than right hand pictures and also than those of men. These findings suggest that both men and women mainly perform the hand mental rotation task with implicit motor imagery. On the other hand, the gender difference in performance might be explained by the difference in balance with other strategies, such as visual imagery, and by cognitive, neurophysiological, and morphological differences

Single-Cell Analysis of the Multicellular Ecosystem in Viral Carcinogenesis by HTLV-1

成人T細胞白血病リンパ腫の多段階発がん分子メカニズムを解明 --難治性疾患の新規治療標的候補を複数同定--. 京都大学プレスリリース. 2021-09-07.Premalignant clonal expansion of human T-cell leukemia virus type-1 (HTLV-1)–infected cells occurs before viral carcinogenesis. Here we characterize premalignant cells and the multicellular ecosystem in HTLV-1 infection with and without adult T-cell leukemia/lymphoma (ATL) by genome sequencing and single-cell simultaneous transcriptome and T/B-cell receptor sequencing with surface protein analysis. We distinguish malignant phenotypes caused by HTLV-1 infection and leukemogenesis and dissect clonal evolution of malignant cells with different clinical behavior. Within HTLV-1–infected cells, a regulatory T-cell phenotype associates with premalignant clonal expansion. We also delineate differences between virus- and tumor-related changes in the nonmalignant hematopoietic pool, including tumor-specific myeloid propagation. In a newly generated conditional knockout mouse model recapitulating T-cell–restricted CD274 (encoding PD-L1) gene lesions found in ATL, we demonstrate that PD-L1 overexpressed by T cells is transferred to surrounding cells, leading to their PD-L1 upregulation. Our findings provide insights into clonal evolution and immune landscape of multistep virus carcinogenesis

Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

成人T細胞白血病リンパ腫（ATL）におけるゲノム情報と臨床情報を統合したリスクモデルを確立 --ATLの個別化医療を推進--. 京都大学プレスリリース. 2023-04-10.The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment. To identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and high-risk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] 5.46, p < 0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR 2.33, p = 0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATL-PI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (−4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (−2), and GATA3 (−3)

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

Response time differences between men and women during hand mental rotation.

This study explored gender differences in correct response rates and response times on a task involving left or right arrow selection and another involving the transformation of mental rotation of the hand. We recruited 15 healthy, right-handed men (age 24.5 ± 6.4) and 15 healthy, right-handed women (age 21.3 ± 4.9). For the tasks, we used pictures of left and right arrows and 32 hand pictures (left and right, palm and back) placed in cons (each at 45° from 0° to 315°). Hand and arrow pictures alternated and were shown at random. Participants decided as quickly as possible whether each picture was left or right. To compare the time taken for the transformation of mental rotation of the hand, we subtracted the average arrow response time from that for the left and right hand pictures for each participant. Correct response rates did not differ significantly between men and women or left and right for either arrow or hand pictures. Regardless of gender, the response time was longer for the left arrow picture than right arrow picture. The response time for the hand picture was longest for both men and women for pictures at rotation angles that were most difficult to align with participants' hands. While there was no difference between men's responses for left and right hand pictures, the responses of women were longer for left than right hand pictures and also than those of men. These findings suggest that both men and women mainly perform the hand mental rotation task with implicit motor imagery. On the other hand, the gender difference in performance might be explained by the difference in balance with other strategies, such as visual imagery, and by cognitive, neurophysiological, and morphological differences

Mental rotation 反応時間と利き目の関係

【序論】Mental rotation (以下,MR) とは, 3次元空間で自由に回転する図形が何であるのかを照合する心的活動である.リハビリテーション領域においても治療的介入手段として,MR の基礎研究・臨床応用が進められている. 身体部位を用いた回転画像を提示した時の反応時間は, 回転角度の増加に伴い遅延すると報告している. 反応時間は, 加齢やスポーツ実施などによる影響があると報告されている. このように年齢や表示角度に関するMR の関連については報告がみられているが, 視覚情報の入力に関与すると思われる眼機能(利き目) とMR との関係を報告した論文は少ない. したがって, 本研究では身体部位である手の回転画像を用いて,これまでに報告されてきたMR 反応時間と性差,利き手との関連に加え,利き目の属性との関連を検討することを目的とした. 【方法】本研究は群馬大学倫理審査委員会により承認された. 対象は103名の健常大学生(平均年齢20.9±2.2歳,男性51名,女性52名,右利き目者59 名,左利き目者44名) であった.課題は両手の画像が0°, 90°, 180°, 270°回転してある32枚の写真によって構成され, それらの写真がランダムにPC の画面に表示された. 被験者は画像を見て, それが右手なのか左手なのかをPC のキーを押すことで回答し,MR 反応時間と回答が記録された.統計解析は一元配置分散分析,独立したt 検定を行った.解析には統計ソフトIBM SPSS Statistics 20を使用し, 有意水準を5％とした. 【結果】MR 反応時間は, 回転角度の180°と0°, 90°, 270°間で有意差がみられた(p＜0.05). 利き目では有意差がみられたが(p＜0.05), 性別, 利き手では有意差はなかった. 【考察】MR 反応時間は性別, 利き手ではなく利き目と関連があることが示唆された. すなわちMR に関連する情報処理過程は利き目によって異なることが示唆された

Mental rotation 反応時間と利き目の関係

【序論】Mental rotation (以下,MR) とは, 3次元空間で自由に回転する図形が何であるのかを照合する心的活動である.リハビリテーション領域においても治療的介入手段として,MR の基礎研究・臨床応用が進められている. 身体部位を用いた回転画像を提示した時の反応時間は, 回転角度の増加に伴い遅延すると報告している. 反応時間は, 加齢やスポーツ実施などによる影響があると報告されている. このように年齢や表示角度に関するMR の関連については報告がみられているが, 視覚情報の入力に関与すると思われる眼機能(利き目) とMR との関係を報告した論文は少ない. したがって, 本研究では身体部位である手の回転画像を用いて,これまでに報告されてきたMR 反応時間と性差,利き手との関連に加え,利き目の属性との関連を検討することを目的とした. 【方法】本研究は群馬大学倫理審査委員会により承認された. 対象は103名の健常大学生(平均年齢20.9±2.2歳,男性51名,女性52名,右利き目者59 名,左利き目者44名) であった.課題は両手の画像が0°, 90°, 180°, 270°回転してある32枚の写真によって構成され, それらの写真がランダムにPC の画面に表示された. 被験者は画像を見て, それが右手なのか左手なのかをPC のキーを押すことで回答し,MR 反応時間と回答が記録された.統計解析は一元配置分散分析,独立したt 検定を行った.解析には統計ソフトIBM SPSS Statistics 20を使用し, 有意水準を5％とした. 【結果】MR 反応時間は, 回転角度の180°と0°, 90°, 270°間で有意差がみられた(p＜0.05). 利き目では有意差がみられたが(p＜0.05), 性別, 利き手では有意差はなかった. 【考察】MR 反応時間は性別, 利き手ではなく利き目と関連があることが示唆された. すなわちMR に関連する情報処理過程は利き目によって異なることが示唆された