73 research outputs found
HSP90α plays an important role in piRNA biogenesis and retrotransposon repression in mouse
HSP90, found in all kingdoms of life, is a major chaperone protein regulating many client proteins. We demonstrated that HSP90α, one of two paralogs duplicated in vertebrates, plays an important role in the biogenesis of fetal PIWI-interacting RNAs (piRNA), which act against the transposon activities, in mouse male germ cells. The knockout mutation of Hsp90α resulted in a large reduction in the expression of primary and secondary piRNAs and mislocalization of MIWI2, a PIWI homolog. Whereas the mutation in Fkbp6 encoding a co-chaperone reduced piRNAs of 28–32 nucleotides in length, the Hsp90α mutation reduced piRNAs of 24–32 nucleotides, suggesting the presence of both FKBP6-dependent and -independent actions of HSP90α. Although DNA methylation and mRNA levels of L1 retrotransposon were largely unchanged in the Hsp90α mutant testes, the L1-encoded protein was increased, suggesting the presence of post-transcriptional regulation. This study revealed the specialized function of the HSP90α isofom in the piRNA biogenesis and repression of retrotransposons during the development of male germ cells in mammals
Sequence divergence and retrotransposon insertion underlie interspecific epigenetic differences in primates
内在性レトロウイルス配列によってヒトのエピゲノムが変化してきたことを発見! --ヒトとチンパンジーのiPS細胞の比較解析から--. 京都大学プレスリリース. 2022-10-12.Changes in the epigenome can affect the phenotype without the presence of changes in the genomic sequence. Given the high identity of the human and chimpanzee genome sequences, a substantial portion of their phenotypic divergence likely arises from epigenomic differences between the two species. In this study, the transcriptome and epigenome were determined for induced pluripotent stem cells (iPSCs) generated from human and chimpanzee individuals. The transcriptome and epigenomes for trimethylated histone H3 at lysine-4 (H3K4me3) and lysine-27 (H3K27me3) showed high levels of similarity between the two species. However, there were some differences in histone modifications. Although such regions, in general, did not show significant enrichment of interspecies nucleotide variations, gains in binding motifs for pluripotency-related transcription factors, especially POU5F1 and SOX2, were frequently found in species-specific H3K4me3 regions. We also revealed that species-specific insertions of retrotransposons, including the LTR5_Hs subfamily in human and a newly identified LTR5_Pt subfamily in chimpanzee, created species-specific H3K4me3 regions associated with increased expression of nearby genes. Human iPSCs have more species-specific H3K27me3 regions, resulting in more abundant bivalent domains. Only a limited number of these species-specific H3K4me3 and H3K27me3 regions overlap with species-biased enhancers in cranial neural crest cells, suggesting that differences in the epigenetic state of developmental enhancers appear late in development. Therefore, iPSCs serve as a suitable starting material for studying evolutionary changes in epigenome dynamics during development
Analysis of the Spray Characteristics of Water and Water/Glycerin Mixtures using an Interferometric Laser Imaging for Droplet Sizing Technique
Injection characteristics play an important role in the emission and overall thermal efficiency of an engine. Several methods have been proposed for analyzing different fuel injection characteristics. This study focused on the interferometric laser imaging for droplet sizing (ILIDS) technique to investigate the effects of droplet size and velocity under different conditions of waterglycerin mixtures. These effects were evaluated using intermittent spray flows in both ambient and pressurized constant volume spray chamber conditions. The initial results were compared to those reported by previous studies and used to determine the Sauter mean diameter (SMD), arithmetic mean diameter (AMD), droplet velocity, and probability density function of the spray droplet size. SMD and AMD tended to decrease as the plate temperature, injection pressure, and viscosity were increased at specific observation areas. The average velocity of the droplet increased with higher plate temperature and injection pressure at specific observation areas. The distribution of the smaller droplet increased with higher plate temperature and injection pressure. For the waterglycerin mixture, as the glycerin ratio increased, more viscous droplets were created. This was followed in higher nozzle shear force at the outlet of the fuel injector, which decreased the particle size and generated more atomized fuel sprays. This result can enable the reduction in hydrocarbon and carbon monoxide emissions from internal combustion engines
I-131 uptake in a thymic cyst
A 61-year-old woman after total thyroidectomy for papillary thyroid cancer underwent I-131 therapy. Focal uptake was seen in the chest on whole body imaging. SPECT/CT delineated I-131 accumulation in an isodense mediastinal lesion which was histologically diagnosed as a thymic cyst. I-131 uptake in a thymic cyst is rare and should be included in the gamut of false-positive entities of I-131 scintigraphy. Copyright © 2010 by Lippincott Williams & Wilkins
Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis
Histone H3 lysine 9 (H3K9) methylation is unevenly distributed in mammalian chromosomes. However, the molecular mechanism controlling the uneven distribution and its biological significance remain to be elucidated. Here, we show that JMJD1A and JMJD1B preferentially target H3K9 demethylation of gene-dense regions of chromosomes, thereby establishing an H3K9 hypomethylation state in euchromatin. JMJD1A/JMJD1B-deficient embryos died soon after implantation accompanying epiblast cell death. Furthermore, combined loss of JMJD1A and JMJD1B caused perturbed expression of metabolic genes and rapid cell death in embryonic stem cells (ESCs). These results indicate that JMJD1A/JMJD1B-meditated H3K9 demethylation has critical roles for early embryogenesis and ESC maintenance. Finally, genetic rescue experiments clarified that H3K9 overmethylation by G9A was the cause of the cell death and perturbed gene expression of JMJD1A/JMJD1B-depleted ESCs. We summarized that JMJD1A and JMJD1B, in combination, ensure early embryogenesis and ESC viability by establishing the correct H3K9 methylated epigenome
Fusion of SPECT and multidetector CT images for accurate localization of pelvic sentinel lymph nodes in prostate cancer patients
金沢大学大学院医学系研究科OBJECTIVE: The present study was performed to investigate the feasibility of fusion of images obtained by SPECT and multidetector CT (MDCT) for the accurate localization of sentinel lymph nodes in prostate cancer patients. METHODS: To facilitate the fusion of both SPECT and CT images, a pelvic MDCT scan was performed with 3 markers of small plastic bullets attached to the skin over the bilateral iliac crests and the ventral midline at the same height. SPECT was performed after the same locations were marked with needle caps containing (99m)Tc-pertechnetate. The images were superimposed by use of free software (MRIcro). The results of hot lymph node detection with fusion images were compared with those of surgery. RESULTS: The images could be successfully superimposed for all 11 patients examined. Surgeons accurately confirmed 27 (87.1%) of 31 regional lymph nodes on fusion images. CONCLUSION: Fusion of SPECT and MDCT images is useful for the precise localization of sentinel lymph nodes in prostate cancer patients
Iron-heme-Bach1 axis is involved in erythroblast adaptation to iron deficiency
Iron plays the central role in oxygen transport by erythrocytes as a constituent of heme and hemoglobin. The importance of iron and heme is also to be found in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is deactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1−/− mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1−/− mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin
Genetic Evidence That the Non-Homologous End-Joining Repair Pathway Is Involved in LINE Retrotransposition
Long interspersed elements (LINEs) are transposable elements that proliferate within eukaryotic genomes, having a large impact on eukaryotic genome evolution. LINEs mobilize via a process called retrotransposition. Although the role of the LINE-encoded protein(s) in retrotransposition has been extensively investigated, the participation of host-encoded factors in retrotransposition remains unclear. To address this issue, we examined retrotransposition frequencies of two structurally different LINEs—zebrafish ZfL2-2 and human L1—in knockout chicken DT40 cell lines deficient in genes involved in the non-homologous end-joining (NHEJ) repair of DNA and in human HeLa cells treated with a drug that inhibits NHEJ. Deficiencies of NHEJ proteins decreased retrotransposition frequencies of both LINEs in these cells, suggesting that NHEJ is involved in LINE retrotransposition. More precise characterization of ZfL2-2 insertions in DT40 cells permitted us to consider the possibility of dual roles for NHEJ in LINE retrotransposition, namely to ensure efficient integration of LINEs and to restrict their full-length formation
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