Effectsof Nifedipine , 8-(N,N-Diethylamino)Octyl-3 ,4,5- Trimethoxybenzoate Hydrochloride andAtrialNatriuretic Peptide on Endothelin-Induced Antinatriuresis in Dogs

ABSTRACT octyl-3,4,5-trimethoxybenzoate hydroch@de (TMB-8) or atrial natiiuretlc peptlde (ANP) was infused Into the renal artery before and during intrarenal arte@a1 Infusionof endothelin-1(El) in anesthetizeddogs. Before El infusion, nifedipine (0.1 @t9 kg1 min'), TMB-8 (75 @ig kg1 min1) or ANP (10 ng kg1 min') increased the urine flow rate, urinary sodium excretion and fractional sodium excretion with little change in renal blood flow or glomerular filtratlon rate. ET (2 ng kg1 m1n1) reØucedthe basal renal t@oodflow, glomerular filtra tion rate, urine flow rate, urinary sodium excretion and fractional (Cao and Banks, 1990; Goetz et aL, 1988; ET raises the free calciumconcentrationin vascularsmooth Received for publication April 15, 1993. (Yanagisawa et aL, 1988) and in viv

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

Symptomatic low-grade carotid stenosis with intraplaque hemorrhage and expansive arterial remodeling is associated with a high relapse rate refractory to medical treatment.

[BACKGROUND]: Carotid plaque characteristics influence future risk of stroke considerably. However, the severity of stenosis does not accurately reflect plaque burden in patients with expansive arterial remodeling. [OBJECTIVE]: To determine the therapeutic outcome of symptomatic carotid low-grade stenosis with vulnerable plaque based on magnetic resonance imaging (MRI) characterization. [METHODS]: We studied 25 (male, n = 23; age, 74.2 ± 5.6 years) of 29 consecutive patients with symptomatic carotid low-grade stenosis (<50%) and both high-signal plaque and expansive remodeling on T1-weighted MRIs. The remaining 4 were excluded because of impending stroke. A single antithrombotic and statin were administered, and recurrent ischemic stroke was treated with dual antithrombotics. We considered carotid endarterectomy when recurrence was refractory to aggressive medical treatment. [RESULTS]: During a 31.3 ± 16.4-month follow-up, 11 of the 25 patients developed a total of 30 recurrent ischemic events (46.0% per patient-year). The patients' characteristics did not differ significantly between the groups with and without recurrence (n = 11 and n = 14, respectively). Seven of 11 patients in the recurrence group treated with carotid endarterectomy remained free of ischemic events during a postoperative follow-up of 19.1 ± 14.6 months. [CONCLUSION]: Symptomatic low-grade carotid stenosis with vulnerable plaque confirmed by MRI was associated with a high rate of stroke recurrence that was refractory to aggressive medical treatment. However, carotid endarterectomy was safe and effective for such patients. Plaque characterization by MRI has the potential for more accurate stroke risk stratification in the management of carotid low-grade stenosis

Genetic and environmental etiology of stability and changes in self-esteem linked to personality: A Japanese twin study

This study used a behavioral genetic approach to examine the genetic and environmental etiology of stability and changes in self-esteem in relation to personality. Multiple genetic analyses were conducted on a longitudinal dataset of self-esteem and Big Five personality scores among young adult Japanese twins over the course of a decade. There were 1221 individuals for whom data were available on both self-esteem and the Big Five personality test at Time 1 and 365 at Time 2. The mean interval between the two times was 9.95 years. Genetic effects on self-esteem were robust, and the same genes were responsible for the stability of self-esteem in individuals over time. Nearly half of the variance in self-esteem was explained by a new genetic factor arising during the decade, suggesting that genetic innovation of self-esteem occurred in early adult life. The genetic and environmental covariance structure between personality and self-esteem in individuals was constant over a decade, providing evidence that the stability of self-esteem was largely attributable to personality. However, genetics for self-esteem independent of personality still contributed to stability over time, differentiating the concept of self-esteem from personality as a trait in terms of its genetic and environmental etiological levels

Fluctuations in the abundance of ammonia oxidizers and the contents of inorganic nitrogen in solarized soil

<p>Solarization makes a great impact on the abundance of ammonia oxidizers and nitrifying activity in soil. To elucidate fluctuations in the abundance of ammonia oxidizers and nitrification in solarized soil, copy numbers of <i>amoA</i> gene of ammonia-oxidizing bacteria (AOB) and archaea (AOA), viable number of ammonia oxidizers and inorganic nitrogen contents were investigated in greenhouse experiments. The copy number of <i>amoA</i> gene and the viable number of ammonia oxidizers were determined by the quantitative polymerase chain reaction and most probable number methods, respectively. Abundance of AOB based on the estimation of <i>amoA</i> gene copy numbers and viable counts of ammonia oxidizers was decreased by the solarization treatment and increased during the tomato (<i>Solanum lycopersicum</i> L.) cultivation period following the solarization. Effect of solarization on the copy number of <i>amoA</i> gene of AOA was less evident than that on AOB. The proportion of nitrate in inorganic nitrogen contents was declined by the solarization and increased during the tomato cultivation period following the solarization. Positive correlations were found between the proportion of nitrate in inorganic nitrogen content and the copy number of bacterial or archaeal <i>amoA</i> gene or the viable number of ammonia oxidizers; the copy number of bacterial <i>amoA</i> gene showed a strong correlation with the viable number of ammonia oxidizers. The present study revealed influences of solarization on the fluctuation in the abundance of ammonia oxidizers and dynamics of inorganic nitrogen contents in soil and the results indicate that the determination of <i>amoA</i> gene of AOB is possibly a quick and useful diagnostic technique for evaluating suppression and restoration of nitrification following solarization.</p