Nanopipette with a lipid nanotube as nanochannel

Proceedings of the 7th IEEE International Conference on Nanotechnology, August 2 - 5, 2007, Hong Kon

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

Isolation, Amino Acid Sequences, and Plausible Functions of the Galacturonic Acid-Binding Egg Lectin of the Sea Hare Aplysia kurodai

Egg lectins occur in a variety of animals ranging from mollusks to vertebrates. A few examples of molluscan egg lectins have been reported, including that of the sea hare Aplysia kurodai; however, their biological functions in the egg remain unclarified. We report the isolation, determination of primary structure, and possible functions of A. kurodai lectin (AKL) from the egg mass of A. kurodai. We obtained AKL as an inseparable mixture of isoproteins with a relative molecular mass of approximately 32 kDa by affinity purification. The hemagglutinating activity of AKL against rabbit erythrocytes was inhibited most potently by galacturonic acid and moderately by xylose. Nucleotide sequencing of corresponding cDNA obtained by rapid amplification of cDNA ends (RACE) allowed us to deduce complete amino acid sequences. The mature polypeptides consisted of 218- or 219-amino acids with three repeated domains. The amino acid sequence had similarities to hypothetical proteins of Aplysia spp., or domain DUF3011 of uncharacterized bacterial proteins. AKL is the first member of the DUF3011 family whose function, carbohydrate recognition, was revealed. Treatment of the egg with galacturonic acid, an AKL sugar inhibitor, resulted in deformation of the veliger larvae, suggesting that AKL is involved in organogenesis in the developmental stage of A. kurodai

Suppression of Salt Precipitation in Membrane Electrode Assembly Electrolyzers for CO2 reduction reactions by Intermittent Supply of Alkali Metal Cations

The electrolysis of CO2 into value-added products holds great potential for closing the carbon cycle. A membrane electrode assembly (MEA) that uses solid polymer electrolytes is a critical technology for enhancing the energy efficiency for the CO2 reduction reaction (CO2RR) because a thin electrolyte layer can effectively reduce the ohmic resistance. The stable operation of the CO2RR in MEA-based cells with an anion-exchange membrane (AEM), however, is hindered by the accumulation of bicarbonate salts, which are derived from alkali-metal cations in anolytes, on the cathode side. Therefore, for stable operation of CO2 electrolysis using an MEA-based cell, the amount of alkali-metal cations needs to be reduced. However, the minimal amount of alkali-metal cations required to operate the reaction system has not been elucidated. Quantitative analysis of the amount of alkali-metal cations transported from the anode to the cathode is essential to obtain the insight into the necessary amount for the operation. In this study, we conducted a quantitative evaluation of the correlation between the production of high-value C2+ compounds, such as ethylene and ethanol, and the transported alkali-metal cations. As a result, although the presence of transported alkali-metal cations on the cathode surface significantly contributes to the generation of C2+ compounds, the rate of K+ ion transport did not match the selectivity of C2+. This result suggests a continuous supply of high amount of K+ to the cathode surface is not required for C2+ formation. On the basis of these findings, we achieved a faradaic efficiency (FE) and a partial current density for C2+ of 77% and 230 mA cm−2, respectively, even after switching the anode solution from 0.1 M KHCO3 to a dilute K+ solution (<7 mM) in an MEA-based cell using AEM and Cu nanoparticles as the cathode catalyst. These values of FE and partial current density were almost identical to those when 0.1 M KHCO3 was continuously supplied as the anode solution. Based on this insight, we successfully improved the durability of the system against salt precipitation. The FE for ethylene remained constant for as long as 60 h at 150 mA cm−2 when continuously flowing 0.1 M KHCO3 as anolyte. However, the FE suddenly decreased after 60 h due to the cessation of CO2 gas flow, caused by salt precipitation in the cathode flow channel. On the contrary, by intermittently supplying 0.1 M KHCO3, we confirmed that the amount of visible K+ salt in the cathode flow field remained negligible even after more than 90 hours of stable operation

A Study of the Effectiveness of Risk Management Training : using Example Cases of Intravenous Misinjection of Enteral Nutrients

A大学の2年生,3年生に対し,リスクマネジメント教育の一つとして,経管栄養剤の静脈内誤注入の事例をもとに授業を行い,その教育効果を検討した.授業では,自験例をもとに医療事故の発生状況,その際の対処法を学ぶとともに,静脈内誤注入が起きない経腸栄養ライン誤接続防止システムを供覧し,フェイルセーフの考え方を教授した.この授業の前後で試験を行い,その成績を比較検討した.2年生75名では,授業前・後で,各10±2.5点,18±3.1点であり,3年生11名では各13±3.4点,21±2.4点であった.両学年とも授業後には有意に得点が増加した.また,3年生は2年生に比べ,授業前後とも良い点数であった.しかし,これらの設問のうち,知識の量を問う設問2〜7とそれ以外の問1とを別々に評価したところ,前者においては3年生の方が2年生より有意によい成績であった.しかし,後者においては,3年生と2年生の間に差は認められず,現行教育の問題点の一つと考えられた.We used cases of intravenous misinjection of enteral nutrients to train second and third year nursing college students in risk management. The effect of the training was assessed by a test before and after a 60 minute lesson, where the occurrence of medical malpractice and proper treatment were explained, the preventative system for misconnection of the parenteral nutrition line presented and the concept of fail-safe taught. A test was set before and after the lesson, and the scores compared. The total scores were 10±2.5 points before the lesson and 18±3.1 points after the lesson among 75 second-year students, and 13±3.4 points and 21±2.4 points respectively among 11 third-year students. These data indicate that the scores were increased by the lesson, and the scores of third-year students were significantly better than those of second-year students. However, when the scores for Questions 2-7, which tested volume of knowledge, and Question One, which tested further knowledge, were assessed separately, those for Question One did not differ between second and third year students, indicating a problem with the course in its current state

Physical Activity Earlier in Life Is Inversely Associated With Insulin Resistance Among Adults in Japan

Background: It is known that physical activity affects glucose metabolism. However, there have been no reports on the influence of physical activity earlier in life on subsequent glucose metabolism. Therefore, we analyzed the influence of physical activity in earlier decades of life on insulin resistance in middle aged and older residents in Japan. Methods: The subjects were 6,883 residents of Okazaki City between the ages of 40 and 79 years who underwent physical examinations at the Okazaki City Medical Association Public Health Center from April 2007 through August 2011. They gave informed consent for participation in the study. Data on individual characteristics were collected via a questionnaire and from the health examination records. Fasting blood glucose and insulin levels were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). HOMA-IR >1.6 was considered to indicate insulin resistance for the purpose of logistic regression models. Results: The study sample included 3,683 men and 3,200 women for whom complete information was available. For those who exercised regularly throughout their teens to their 30s–40s, the odds ratio for having insulin resistance was 0.75 (95% confidence interval [CI], 0.58–0.96) for men and 0.76 (95% CI, 0.58–0.99) for women after adjusting for other variables, including age, body mass index, and present physical activity. A linear trend was also observed in both men and women. Conclusions: Subjects who have exercised regularly in the early decades of life are less likely to have insulin resistance later in life