Observation of the FeO2 and FeIVO stretching Raman bands for dioxygen reduction intermediates of cytochrome bo isolated from Escherichia coli

AbstractReaction intermediates in dioxygen reduction by the E. coli cytochrome bo-type ubiquinol oxidase were studied by time-resolved resonance Raman spectroscopy using the artificial cardiovascular system. At 0–20 μs following photolysis of the enzyme—CO adduct in the presence of O2, we observed the FeO2 stretching Raman band at 568 cm−1 which shifted to 535 cm−1 with the 18O2 derivative. These frequencies are remarkably close to those of other oxyhemoproteins including dioxygen-bound hemoglobin and aa3-type cytochrome c oxidase. In the later time range (20–40 μs), other oxygen-isotope-sensitive Raman bands were observed at 788 and 361 cm−1. Since the 781 cm−1 band exhibited a downshift by 37 cm−1 upon 18O2 substitution, we assigned it to the FeIVO stretching mode. This band is considered to arise from the ferryl intermediate, but its appearance was much earlier than the corresponding intermediate of bovine cytochrome c oxidase (> 100 μs). The 361 cm−1 band showed the 16O/18O isotopic frequency shift of 14 cm−1 similar to the case of bovine cytochrome c oxidase reaction

Reconstructing visual illusory experiences from human brain activity

Visual illusions provide valuable insights into the brain’s interpretation of the world given sensory inputs. However, the precise manner in which brain activity translates into illusory experiences remains largely unknown. Here, we leverage a brain decoding technique combined with deep neural network (DNN) representations to reconstruct illusory percepts as images from brain activity. The reconstruction model was trained on natural images to establish a link between brain activity and perceptual features and then tested on two types of illusions: illusory lines and neon color spreading. Reconstructions revealed lines and colors consistent with illusory experiences, which varied across the source visual cortical areas. This framework offers a way to materialize subjective experiences, shedding light on the brain’s internal representations of the world

Glucagon-like Peptide-1 Suppresses the Proliferation and Migration of Vascular Smooth Muscle Cells: Implications for Preventive Effects on Atherosclerosis

Our group previously demonstrated the suppressive effect of glucagon-like peptide-1 (GLP-1) on macrophage-driven atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. In the present study we investigated the suppressive effect of GLP-1 on the atherogenic phenotype of vascular smooth muscle cells (VSMCs) in vivo using apoE-/- mice, and the proliferation and migration of human VSMCs in vitro. A 4-week infusion of GLP-1 in 17-week-old apoE-/- mice significantly reduced the proliferative VSMC phenotype stained with SMemb. Platelet-derived growth factor (PDGF) -BB significantly stimulated the proliferation of human aortic VSMCs by three fold. Both 0.1 and 1nmol/l GLP-1 significantly suppressed the PDGF-induced VSMC proliferation, and this suppressive effect was significantly abolished by the GLP-1 receptor antagonist exendin (9-39) (50nmol/l). The GLP-1 receptor agonists liraglutide (100nmol/l) and exendin-4 (100nmol/l) mimicked GLP-1, significantly suppressing PDGF-induced VSMC proliferation. PDGF-BB significantly stimulated the migration of human aortic VSMCs by 1.7 -fold, and this effect was significantly suppressed by 1nmol/l GLP-1. These findings suggest that GLP-1-related treatments may prevent the progression of atherosclerotic lesions by suppressing the proliferation and migration of VSMCs, which are characteristic features of atherosclerosis

Involvement of Vascular Endothelial Cells in the Anti-atherogenic Effects of Liraglutide in Diabetic Apolipoprotein E-null Mice

Glucagon-like peptide 1 receptor agonists （GLP-1RAs） have been shown to exert anti-atherosclerotic effects via multiple mechanisms on different types of cells. However, it is unclear which of these mechanisms are crucial. We investigated the role of vascular endothelial cells （VECs） in the anti-atherogenic effects of the GLP-1RA liraglutide in a mouse model of atherosclerosis. Streptozotocin-induced diabetic apolipoprotein E-null mice were randomly assigned to treatment with either vehicle （saline） or liraglutide （107nmol/kg/day）, and were subjected to femoral artery wire injury to remove VECs. After 4 weeks, vessel samples were collected for analysis. Streptozotocin-injected mice had fasting plasma glucose levels of ＞300mg/dl and hemoglobin A1c levels of ＞9％, indicating that the injections had induced severe hyperglycemia. However, there were no differences in metabolic characteristics such as levels of hemoglobin A1c, fasting plasma glucose, total cholesterol, and triglycerides between the vehicle and liraglutide groups. Analysis of atherosclerotic plaque formation revealed that liraglutide treatment significantly suppressed plaque formation in the aorta. In addition, liraglutide treatment reduced plaque volume and intra-plaque macrophage accumulation at the aortic sinus. Furthermore, liraglutide treatment suppressed vascular expression of pro-inflammatory cytokines. In uninjured femoral arteries, no plaques were observed; however, severe plaque formation occurred in femoral arteries that had been injured by wire insertion to remove VECs. Unlike in the uninjured aorta, liraglutide treatment did not affect plaque volume or arterial remodeling （intimal and medial thinning, and arterial dilation） in wire-injured femoral arteries. Of the various cells that liraglutide affects, VECs play a central role in liraglutide’s anti-atherogenic effects in diabetic mice

Associations of Glucose and Blood Pressure Variability with Cardiac Diastolic Function in Patients with Type 2 Diabetes Mellitus and Hypertension: A Retrospective Observational Study

We evaluated the effects of glucose metabolism and blood pressure（BP） variability on cardiac diastolic function in patients with type 2 diabetes mellitus（T2DM） and hypertension. A total of 23 inpatients with T2DM underwent ambulatory BP monitoring（ABPM） and echocardiography. BP variability was assessed by measuring the mean BP and the standard deviation（SD） of systolic and diastolic BP over 24 hours, as well as daytime and nighttime ABPM. Cardiac diastolic function was assessed using the echocardiography E/e′ ratio. Participants had a mean age of 69.0±10.6 years, disease duration of 11.0±10.5 years, glycated hemoglobin（HbA1c） of 8.2％±1.3％, and glycated albumin（GA） of 22.0％±4.2％. Univariate analysis showed that the nighttime systolic BP, nighttime SDs of systolic and diastolic BP, urinary albumin, estimated glomerular filtration rate, and GA/HbA1c ratio were all significantly correlated with the E/e′ ratio. Moreover, stepwise multiple regression analysis identified nighttime SD of diastolic BP, urinary albumin, and GA/HbA1c ratio as independent contributors to the E/e′ ratio. In patients with T2DM and hypertension, cardiac diastolic function was associated with nighttime diastolic BP variability and the GA/HbA1c ratio

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