Community composition and methane oxidation activity of methanotrophs associated with duckweeds in a fresh water lake

Methanotrophs are the only biological sink of the greenhouse gas methane. To understand the ecological features of methanotrophs in association with plants in the methane emitting environments, we investigated the community composition and methane oxidation of methanotrophs associated with duckweeds in a fresh water lake. Duckweeds collected from Lake Biwa, Japan over three summers showed methane consumption activity between 0.0067 and 0.89 μmol h⁻¹ g⁻¹ (wet weight), with the highest values occurring from the end of July to August. The methanotrophic community on duckweeds consisted primarily of γ-proteobacterial groups including the genera Methylomonas and Methylocaldum. Further analysis of co-cultures of a methanotroph isolate with sterilized duckweed revealed that the duckweed plant as well as the duckweed spent culture supernatant exerted an enhancing effect on methane oxidation. These results indicate that duckweeds not only provide a habitat for methanotrophs but also stimulate methanotrophic growth

Oncolytic Virus-Mediated Targeting of the ERK Signaling Pathway Inhibits Invasive Propensity in Human Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) cells have an exceptional ability to invade nerves through pronounced crosstalk between nerves and cancer cells; however, the mechanism of PDAC cell invasion remains to be elucidated. Here, we demonstrate the therapeutic potential of telomerase-specific oncolytic adenoviruses, OBP -301 and tumor suppressor p53-armed OBP-702, against human PDAC cells. Highly invasive PDAC cells exhibited higher levels of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) expression independent of KRAS expression; ERK1/2 inhibitor or small interfering RNA (siRNA) treatment significantly reduced the migration and invasion of PDAC cells, suggesting that the ERK signaling pathway is associated with the invasiveness of PDAC cells. OBP-702 infection suppressed ERK signaling and inhibited PDAC cell migration and invasion more efficiently than OBP-301. OBP-702 also effectively inhibited PDAC cell invasion even when invasiveness was enhanced by administration of motility stimulators, such as nerve and neurosecretory factors. Moreover, noninvasive whole-body imaging analyses showed that OBP-702 significantly suppressed tumor growth in an orthotopic PDAC xenograft model, although both viruses were equally effective against subcutaneous tumors, suggesting that OBP-702 can influence the orthotopic tumor microenvironment. Our data suggest that oncolytic virus-mediated disruption of ERK signaling is a promising antitumor strategy for attenuating the invasiveness of PDAC cells

Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice

Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)–like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)–fed mice. Glucoraphanin supplementation attenuated weight gain, decreased hepatic steatosis, and improved glucose tolerance and insulin sensitivity in HFD-fed wild-type mice but not in HFD-fed Nrf2 knockout mice. Compared with vehicle-treated controls, glucoraphanin-treated HFD-fed mice had lower plasma lipopolysaccharide levels and decreased relative abundance of the gram-negative bacteria family Desulfovibrionaceae in their gut microbiomes. In HFD-fed mice, glucoraphanin increased energy expenditure and the protein expression of uncoupling protein 1 (Ucp1) in inguinal and epididymal adipose depots. Additionally, in this group, glucoraphanin attenuated hepatic lipogenic gene expression, lipid peroxidation, classically activated M1-like macrophage accumulation, and inflammatory signaling pathways. By promoting fat browning, limiting metabolic endotoxemia-related chronic inflammation, and modulating redox stress, glucoraphanin may mitigate obesity, insulin resistance, and NAFLD

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

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water-soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (kfv for fluvastatin, and kpv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with kfv and kpv of 4.82 M−1s−1 and 49.0 M−1s−1, respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both kfv and kpv were >109 M−1s−1. Fluvastatin also eliminated tert-butyl peroxyl radical with relative kfv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert-butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with kfv and kpv of 68.6 M−1s−1 and 701 M−1s−1, respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert-butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids

自治体の防災に貢献する地震情報の構築と提供―GISによるデータベースの構築―

自治体や住民に貢献する地震情報の構築とその伝達手法の開発を目的とする．そのためには，まず基礎となるデータベースの構築が必要となる．本報告は，鳥取県を対象とした地震防災に関する情報のデータベース化についての報告である．データベース化にはGISを利用した．基本的な地図情報，地震防災に関連する震源，地盤構造，地下水観測情報についての説明，地震発生の特徴について震源，地盤情報を用いた解析例を示す．Working with Tottori prefecture as a target area, we prepared a basic database ofinformation for earthquake disaster prevention. Using GIS software, we created adatabase of information for earthquake disaster prevention, which includes hypocenterand seismic wave data, geological data, geophysical exploration data, and hotspring andgroundwater data. We analyzed these data and tried to estimate several features of thetarget area to help reduce earthquake damage.自治体や住民に貢献する地震情報の構築とその伝達手法の開発を目的とする．そのためには，まず基礎となるデータベースの構築が必要となる．本報告は，鳥取県を対象とした地震防災に関する情報のデータベース化についての報告である．データベース化にはGISを利用した．基本的な地図情報，地震防災に関連する震源，地盤構造，地下水観測情報についての説明，地震発生の特徴について震源，地盤情報を用いた解析例を示す．Working with Tottori prefecture as a target area, we prepared a basic database ofinformation for earthquake disaster prevention. Using GIS software, we created adatabase of information for earthquake disaster prevention, which includes hypocenterand seismic wave data, geological data, geophysical exploration data, and hotspring andgroundwater data. We analyzed these data and tried to estimate several features of thetarget area to help reduce earthquake damage

Seismometric Observations of Matsushiro Swarm Earthquakes

This paper is the report of seismometric observations of Matsushiro swarm earthquakes made by Abuyama Seismological Observatory and Disaster Prevention Research Institute, independently or co-operatively. Continuous observation at Shinko has been carried out to investigate the time variation of the seismic activity since the joint observation of ultramicro-earthquakes at the end of 1965. As the seismicity became active, continuous observation was started at Sanada, too, on June, 1966, with the main purpose of investigating the "Ishimoto-Iida's relation" and the time variation of seismic activity, but it was abandoned on September, 1966 because of overlapping the station with that of the Earthquake Research Institute. For studying the attenuation of seismic wave in short hypocentral distance and formulating the equation for calculating the magnitude of an earthquake, the Matsushiro swarm earthquakes are a very good source observations. On the basis of this idea, we picked out four observation points on the array line from Matsushiro to Komoro, and installed completely equipped low magnification seismographs of displacement type. The observations were begun on June, 1966. Further, on November the same year, the array line turned about 90 degrees for the first line which was extended from Matsushiro to Toyoshina through Akashina. The observations are still being continued at present. As had been planned in the earthquake prediction program in Japan, mobile observations were carried out three times from June to November, 1966, for the purpose of investigating the field problems of this observation system and the seismic activity outside the so-called seismic region of Matsushiro swarm earthquakes. Although this is a simple method by which only the frequency distribution of S-P duration times were observed, notwithstanding its simplicity the mobile observation system for the purpose of surveying the seismic activity was proved useful in the region where the dense observation network had not then been set up. Though the idea that the earthquakes are almost always generated in the vicinity of the fault is exceedingly Americanized, we carried out the observation of ultramicro-earthquakes by the seismometer-array, with an expectation that some relation between the cracks around Mt. Minakami and ultramicro-earthquakes may exist. However this expectation has been proved completely to the contrary