Metaphorical competence in an EFL context: the mental lexicon and metaphorical competence of Japanese EFL students

This thesis on metaphor and metaphor study covers theoretical and practical issues in the past and the present both in the occidental and oriental worlds. Metaphor in rhetoric, cognitive and applied linguistics is described briefly, mostly as a theoretical issue. It states that metaphor was treated as part of rhetoric in the past, however, recently it has developed more broadly into a facet of human cognition. As a practical issue, professional studies assessing metaphorical competence are highlighted, which inform the measurement of metaphorical competence of Japanese learners of English (Japanese EFL students, hereafter). The author developed her original measurement instruments (tests and evaluations of metaphorical competence) to assess the receptive and productive metaphorical abilities of Japanese EFL students. The tests aims to measure Japanese EFL students' metaphorical competence and discover the answers to what factors affect their comprehension and use of English metaphorical expressions and what kinds of metaphorical expressions are salient or opaque for them. This study showed that the Japanese EFL students' receptive ability was better than their productive ability. It further indicated that the size of their mental lexicons, the elasticity of their linguistic ability, the degree of semantic expansion, and their cognitive flexibility (e.g. analogical reasoning, mapping and networking) were important factors affecting their ability to handle metaphorical expressions. Another important discovery was that L1 transfer might play an ambivalent role. As for the salience and opacity of metaphorical expressions, the degree of clarity of expressions was an important element. For example, the expressions with images easy to visualise were the easiest for the Japanese EFL students to understand and use metaphorically. The highly conventional idioms involving metaphorical meanings were problematic for them to understand and especially to use

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

Metaphorical competence in an EFL context : the mental lexicon and metaphorical competence of Japanese EFL students

This thesis on metaphor and metaphor study covers theoretical and practical issues in the past and the present both in the occidental and oriental worlds. Metaphor in rhetoric, cognitive and applied linguistics is described briefly, mostly as a theoretical issue. It states that metaphor was treated as part of rhetoric in the past, however, recently it has developed more broadly into a facet of human cognition. As a practical issue, professional studies assessing metaphorical competence are highlighted, which inform the measurement of metaphorical competence of Japanese learners of English (Japanese EFL students, hereafter). The author developed her original measurement instruments (tests and evaluations of metaphorical competence) to assess the receptive and productive metaphorical abilities of Japanese EFL students. The tests aims to measure Japanese EFL students' metaphorical competence and discover the answers to what factors affect their comprehension and use of English metaphorical expressions and what kinds of metaphorical expressions are salient or opaque for them. This study showed that the Japanese EFL students' receptive ability was better than their productive ability. It further indicated that the size of their mental lexicons, the elasticity of their linguistic ability, the degree of semantic expansion, and their cognitive flexibility (e.g. analogical reasoning, mapping and networking) were important factors affecting their ability to handle metaphorical expressions. Another important discovery was that L1 transfer might play an ambivalent role. As for the salience and opacity of metaphorical expressions, the degree of clarity of expressions was an important element. For example, the expressions with images easy to visualise were the easiest for the Japanese EFL students to understand and use metaphorically. The highly conventional idioms involving metaphorical meanings were problematic for them to understand and especially to use.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Syntaxin 1B, but not syntaxin 1A, is necessary for the regulation of synaptic vesicle exocytosis and of the readily releasable pool at central synapses.

Two syntaxin 1 (STX1) isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t)-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission

Properties of evoked EPSCs in STX1B^−/− neurons.

<p>(A) Representative mean eEPSC waveforms in WT and STX1B^−/− synapses (left). Neurons were stimulated at 25 ms intervals. Amplitude of AMPA receptor-mediated eEPSCs of STX1B^−/− (<i>n</i> = 18) and WT (<i>n</i> = 22) neurons (right). Scale bar: 50 ms. (B) Paired-pulse ratio of EPSCs was significantly different in cultured neurons from STX1B^−/− and WT mice (WT, <i>n</i> = 19; STX1B^−/−, <i>n</i> = 14; <i>p</i> = 0.049, one-way repeated measure ANOVA with two sample <i>t</i>-test). (C) Amplitude of individual eEPSCs during the stimulus train triggered by 200 stimuli at 1 Hz from STX1B^−/− (<i>n</i> = 7) and WT (<i>n</i> = 16) mice, normalized to the amplitude of first response and plotted as a function of stimulus number. (D) Representative eEPSC train stimulated by 20 Hz, recorded from a representative WT (top) and STX1B^−/− (bottom) neuron. The first (left) and last (right) twenty responses are presented. Stimulus artifacts were truncated. Scale bar: 0.5 s, 0.5 nA. (E) Amplitude of individual eEPSCs during the stimulus train triggered by 200 stimuli at 20 Hz. A significant difference between neurons from STX1B^−/− and WT mice was observed (WT, <i>n</i> = 7; STX1B^−/−, <i>n</i> = 8; <i>p</i><0.001, one-way repeated measure ANOVA). (F) Mean cumulative EPSC amplitude value from 40 stimuli, 20 Hz trains in WT and STX1B^−/− neurons. Data points between stimuli 30 and 40 (top) and 180 and 200 (bottom) were fitted by linear regression and back-extrapolated to time 0 to estimate the vesicle pool size.</p