Phototriggered protein syntheses by using (7-diethylaminocoumarin-4-yl)methoxycarbonyl-caged aminoacyl tRNAs

The possibility of spatiotemporally photocontrolling translation holds considerable promise for studies on the biological roles of local translation in cells and tissues. Here we report caged aminoacyl-tRNAs (aa-tRNAs) synthesized using a (7-diethylaminocoumarin-4-yl)methoxycarbonyl (DEACM)-cage compound. DEACM-caged aa-tRNA does not spontaneously deacylate for at least 4 h in neutral aqueous solution, and does not bind to the elongation factor Tu. On irradiation at ∼405 nm at 125 mW cm(-2), DEACM-aa-tRNA is converted into active aa-tRNA with a half-life of 19 s. Notably, this rapid uncaging induced by visible light does not impair the translation system. Translation is photoinduced when DEACM-aa-tRNA carrying a CCCG or a CUA anticodon is uncaged in the presence of mRNAs harbouring a CGGG four-base codon or a UAG amber codon, respectively. Protein synthesis is phototriggered in several model systems, including an in vitro translation system, an agarose gel, in liposomes and in mammalian cells

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

Importance to mutual understanding between teacher and volunteer : Focused on activity in the A elementary school of Sagamihara city in Kanagawa prefecture

Today, it has been said that it is very important for family and community as school-support volunteer to work together with the elementary and junior high school for improving educational activities. Especially, in helping children to learn and to put up school events, this volunteer needs to cooperate with them and teachers. In previous studies on this issue, it put emphasis on the importance of acting independently with school, family and community. But we think it is necessary to find out and enhance the sense of educational activities in caring about school, family and community. Therefore, this paper examines the case of the discussion on activities in the small elementary school of Sagamihara city in Kanagawa prefecture. And in this research, we had a few interviews with school principal and teachers, school volunteers. The results are as follows: to understand mutually between school, family and community in educational activities, school and teacher recognize family and community to being brought out the best in children. And family and community view school and teacher as being drawn out the best

Phototriggered protein syntheses by using (7-diethylaminocoumarin-4-yl)methoxycarbonyl-caged aminoacyl tRNAs

The possibility of spatiotemporally photocontrolling translation holds considerable promise for studies on the biological roles of local translation in cells and tissues. Here we report caged aminoacyl-tRNAs (aa-tRNAs) synthesized using a (7-diethylaminocoumarin-4-yl)methoxycarbonyl (DEACM)-cage compound. DEACM-caged aa-tRNA does not spontaneously deacylate for at least 4 h in neutral aqueous solution, and does not bind to the elongation factor Tu. On irradiation at ∼405 nm at 125 mW cm(-2), DEACM-aa-tRNA is converted into active aa-tRNA with a half-life of 19 s. Notably, this rapid uncaging induced by visible light does not impair the translation system. Translation is photoinduced when DEACM-aa-tRNA carrying a CCCG or a CUA anticodon is uncaged in the presence of mRNAs harbouring a CGGG four-base codon or a UAG amber codon, respectively. Protein synthesis is phototriggered in several model systems, including an in vitro translation system, an agarose gel, in liposomes and in mammalian cells

Association between Locomotive Syndrome and Physical Activity in Long-Term Inpatients of Psychiatric Care Wards in Japan: A Preliminary Study

The aim of this cross-sectional study was to determine the status of locomotive syndrome (LS) and the level of physical activity (PA) in long-term inpatients in a psychiatric care ward and to investigate the association between the severity of LS and the level of PA. The study participants consisted of 25 patients aged 55 years or older who had been admitted to a psychiatric care ward for more than one year. The participants’ LS stage was determined and their level of PA was measured using an accelerometer. We also analyzed the correlations between the LS stage test results, level of PA, and values for each assessment item. The LS stage test showed that 84.0% of the participants were at stages 3. The participants’ mean step count was 3089.8 ± 2346.5 steps. The participants’ mean sedentary time was 349.7 ± 68.9 min, which is more than 70% of the total measuring time. Overall, the results indicate that LS stage was significantly correlated to age, ADL, and level of PA. Patients who stay in a psychiatric care ward experience declining motor functioning and lack PA. Deterioration of motor functioning is associated with lack of PA, suggesting the need for physical intervention

Smoking, white blood cell counts, and TNF system activity in Japanese male subjects with normal glucose tolerance

<p>Abstract</p> <p>Background</p> <p>Cigarette smokers have increased white blood cell (WBC) counts and the activation of tumor necrosis factor (TNF). The effect of smoking on WBC counts and TNF system activity, however, has not been separately investigated yet.</p> <p>Subjects and Methods</p> <p>One hundred and forty-two Japanese male subjects with normal glucose tolerance were recruited. They were stratified into two groups based on the questionnaire for smoking: one with current smokers (n = 48) and the other with current non-smokers (n = 94). Whereas no significant differences were observed in age, BMI, high molecular weight (HMW) adiponectin, and TNF-α between the two groups, current smokers had significantly higher soluble TNF receptor 1 (sTNF-R1) (1203 ± 30 vs. 1116 ± 21 pg/ml, <it>p </it>= 0.010) and increased WBC counts (7165 ± 242 vs. 5590 ± 163/μl, <it>p </it>< 0.001) and lower HDL cholesterol (55 ± 2 vs. 60 ± 1 mg/dl, <it>p </it>= 0.031) as compared to current non-smokers. Next, we classified 48 current smokers into two subpopulations: one with heavy smoking (Brinkman index ≥ 600) and the other with light smoking (Brinkman index < 600).</p> <p>Results</p> <p>Whereas no significant difference was observed in age, BMI, HMW adiponectin, WBC counts and TNF-α, sTNF-R1 and sTNF-R2 were significantly higher in heavy smoking group (1307 ± 44 vs. 1099 ± 30 pg/ml, <it>p </it>< 0.001; 2166 ± 86 vs. 827 ± 62 pg/ml, <it>p </it>= 0.005) than in light smoking group, whose sTNF-R1 and sTNF-R2 were similar to non-smokers (sTNF-R1: 1116 ± 15 pg/ml, <it>p </it>= 0.718, sTNF-R2; 1901 ± 32 pg/ml, <it>p </it>= 0.437). In contrast, WBC counts were significantly increased in heavy (7500 ± 324/μl, <it>p </it>< 0.001) or light (6829 ± 352/μl, <it>p </it>= 0.001) smoking group as compared to non-smokers (5590 ± 178/μl). There was no significant difference in WBC counts between heavy and light smoking group (<it>p </it>= 0.158).</p> <p>Conclusion</p> <p>We can hypothesize that light smoking is associated with an increase in WBC counts, while heavy smoking is responsible for TNF activation in Japanese male subjects with normal glucose tolerance.</p