Isolation of a transcriptionally active element of high copy number retrotransposons in sweetpotato genome

Many plant retrotransposons have been characterized, but only three families (Tnt1, Tto1 and Tos17) have been demonstrated to be transpositionally competent. We followed a novel approach that enabled us to identify an active element of the Ty1-copia retrotransposon family with estimated 400 copies in the sweetpotato genome. DNA sequences of Ty1 -copia reverse transcriptase (RTase) from the sweetpotato genome were analyzed, and a group of retrotransposon copies probably formed by recent transposition events was further analyzed. 3’RACE on callus cDNA amplified transcripts containing long terminal repeats (LTR) of this group. The sequence -specific amplification polymorphism (S-SAP) patterns of the LTR sequence in the genomic DNA were compared between a normal plant and callus lines derived from it. A callus -specific S-SAP product was found into which the retrotransposon detected by the 3’RACE had been transposed apparently during cell culture. We conclude that our approach provides an effective way to identify active elements of retrotransposons with high copy numbers.</p

Three-dimensional shapes and distributions of long-period stacking ordered structures in Mg₉₇Zn₁Gd₂ cast alloys characterized by electron tomography

Three-dimensional (3D) configurations of 14H long-period stacking ordered (LPSO) structures formed in Mg97Zn1Gd2 cast alloys at intermediate stages of the formation process have been studied by single tilt-axis electron tomography using high-angle annular dark-field scanning transmission electron microscopy. Lateral morphology of the 14H LPSO is clearly visualized by reconstructing 3D volumes. An existence of "dent-shaped" area was found in a 3D reconstructed volume for the first time. The edge of LPSO shows a characteristic triangular shape with an angle of 60°, which indicates that the growth front is parallel to {112¯0}Mg. It is suggested that in-plane irregular or characteristic shapes are related to the lateral growth mechanism of LPSO. Electron tomography has proven to be an indispensable tool to characterize in-plane structural information of LPSO formed in α-Mg matrix

Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model

Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy

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

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

Magnetic state in the quasi-two-dimensional organic conductor λ-(BEST)2FeCl4 and the path of π-d interaction

Studies of the quasi-two-dimensional organic conductors λ-(D)2MCl4 [D = donor molecules, M = Ga, Fe] have shown that λ-(BETS)2GaCl4 [BETS = bis(ethylenedithio)tetraselenafulvalene] undergoes an unconventional superconducting transition and λ-(BETS)2FeCl4 undergoes a field-induced superconducting transition. In λ-type salts, the interactions between donor molecules and FeCl4- (π-d interactions) are important. To investigate π-d interaction, a pair of magnetic M = Fe and nonmagnetic M = Ga salts which have the same ground state in the donor layer is desired. However, no such pair has been found, and few experimental studies have considered π-d interaction paths. λ-(BEST)2MCl4 [BEST = bis(ethylenediseleno)tetrathiafulvalene] are obtained for both anions, and M = Ga salt shows an antiferromagnetic transition, but the ground state has not been analyzed in M = Fe salt. We perform x-ray diffraction, magnetic susceptibility measurement, and Mossbauer spectroscopy in λ-(BEST)2FeCl4. We find that a magnetic transition is observed at around 26 K. The λ-(BEST)2MCl4 system is a system in which both FeCl4- and GaCl4- salts show antiferromagnetic transitions. In addition, the ethylene motions observed at room temperature are ordered around 108 K, resulting in the establishment of the π-d interaction path between chalcogens and the anion, and low-field magnetization suggests that the π-d interaction in λ-(BEST)2FeCl4 is smaller than that in λ-(BETS)2FeCl4. Our results show that the inner chalcogen of donor molecules is important as the path of the interaction

Identification of Renieramycin A as an Antileishmanial Substance in a Marine Sponge Neopetrosia sp.

The newly developed assay system using recombinant Leishmania amazonensis expressing enhanced green fluorescent protein (La/egfp) has been applied to the screening of Japanese marine sponges for antileishmanial activity. Bioassay-guided fractionation of an active sponge Neopetrosia sp. afforded an active compound which was identified as renieramycin A by spectroscopic analysis. It inhibited La/egfp with an IC50 value of 0.2 μg/mL

Analytical estimation of drift-orbit island-width for passing ions in static magnetic perturbation

The fast ion transport plays a key role in the simulation for developing operational scenarios. But the transport of fast ions in the perturbed field is complex compared with that of thermal ions since the transport depends on energy and pitch angle as well as a spatial coordinate. The Monte-Carlo approach can handle the transport in the straight forward way, however the approach is computationally expensive and is not suitable for scenario simulators. We need a computationally low-cost method or a reduced transport model. The island width in the phase space can be a characteristic scale of the transport. Thus, a simple method to determine the island width is useful to construct a reduced model. In this paper, we present a method to estimate the drift-orbit island-width from the velocity perturbation. We have derived an analytic expression for the drift-orbit island-width on a resonant toroidal canonical angular momentum surface in the same way how we estimate the magnetic island width from the magnetic perturbation on a resonant magnetic poloidal flux surface. Thus, we can avoid the issue, in our previous work, on the difference between the magnetic perturbation and velocity perturbation. We can also eliminate the cost for the Poincaré-map calculation of the magnetic perturbation. The estimated drift orbit island widths were compared with those from Poincaré maps obtained from a drift-orbit-following calculation. The estimated island widths well correlate with those from Poincaré maps within the error of about 15%. The island overlaps are also explained by the estimated island position and its width. The estimation method can provide an indicator to evaluate an overlapping threshold for chaotic orbits in the same way with the magnetic perturbation.The 16th IAEA Technical Meeting on Energetic Particles in Magnetic Confinement Systems - Theory of Plasma Instabilities (EPPI2019