Endogenization and excision of human herpesvirus 6 in human genomes

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactive into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association.In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected "solo-DR scar" has not been describedin vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines

縄文土器3D計測データの復元箇所マスキング処理

　考古資料特有の特徴として、往々にして破片となって出土することがある。これにより、全体が残存せず後補された部分が含まれることがある。こうした復元部分は、データ取得の際にノイズとなり分析結果に影響を与えるため、テクスチャ（色情報）付きの画像から認識することで後補部分の情報を分析対象から排除する必要がある。そこで、本研究ではこれらの復元部分を削除するために特定する方法について考察する。　本研究において、縄文土器の3D計測データの取得にはCreaform 社製の3Dスキャナーを用いて3Dデータとテクスチャデータを取得している。3Dデータはobjフォーマットであり。objフォーマットはWavefront社のAdvanced Visualizerというソフト用のファイルフォーマットとして開発され、現在は多くのCGソフトがサポートし、CGソフトの中間ファイルフォーマットとして広く使用されている。記録される3次元データは、頂点座標値データ、頂点法線ベクトルデータ、テクスチャ座標値データ、凸多角形面データなどである。。クスチャデータは別ファイルのビットマップ画像であり、objフォーマットで指定している三角形のポリゴンに対応した色データが並んだものとなっている。　まずはこのテクスチャデータを用いて復元箇所を特定する手法を考察した。色情報を用いて特定を行うが、通常のRGB色空間ではなく、HSV色空間に変換して処理を行った。色相(Hue)、彩度(Saturation)、明度(Values)の三つの成分からなる色空間となるので、人間が色を知覚する方法が類似しており、ある範囲の色を表すのに都合が良い。特定したい場所の色を数カ所取り出し、そのHSVそれぞれの値の範囲に当てはまる部分の色を用いた。　実験結果から、以下に挙げる点が課題となることが分かった。(1)復元箇所の色は均一でないため、色情報のみで特定することは困難である。(2)復元個所の色が本来の土器と同じ色となる可能性もあり、その場合は間違って対象個所を選定してしまう。　この手法において、テクスチャにおける色情報はポリゴンごとに独立していて、隣り合った領域の情報が失われている。UV展開のようにテクスチャを見た目に近い形で画像として取り出すことができれば、色情報のみではなく、決まった領域内のヒストグラム特徴（平均、分散など）、差分統計量、濃度共起行列（２次統計量）やフーリエ特徴などを用いて、復元箇所の特徴を取り出し、特定することが可能であり、隣接した領域で判断できるので、より正しい特定が可能と思われる。UV展開でなく、側面や上下から見た画像を用いることでも可能になると思われる

Diagnosing nocturnal frontal lobe epilepsy: A case study of two children

AbstractWe describe two children of nocturnal frontal lobe epilepsy (NFLE) diagnosed using carefully observed nocturnal sleep EEGs and detailed patient histories.Case #1, a 14-year-old boy, showed repeated generalized tonic convulsions and frequent eyes opening seizures during sleep. Conventional EEGs – done with the patient awake or in sleep stage I – showed no abnormalities, while a nocturnal sleep EEG – done during in sleep stage II – revealed the repeated, sharp wave bursts predominantly in the right frontal lobe characteristic of NFLE. During these wave bursts, we noticed the boy's eyes opening, although his parents had not been aware this NFLE symptom.Case #2, a 12-year-old boy, showed one daytime generalized convulsion. He had also been suffering from repeated paroxysmal episodes similar to parasomnia – waking up, sitting, walking, screaming, and speaking – which always followed the same patterns lasting several minutes. During the nocturnal sleep EEG, episodes occurred twice, showing abnormal epileptic discharges predominantly in the frontal lobe. His parents did not mention the episodes to us until questioned, as they had recognized them as parasomnia. The previous conventional EEG showed abnormal slow waves in the frontal lobe, which led us to suspect frontal lobe epilepsy and to take a detailed patient history.The frequency and stereotypy of their symptoms during sleep caused us to perform nocturnal sleep EEGs and led us NFLE diagnosis. Detailed patient histories including sleep habits and carefully observed nocturnal sleep EEGs enabled us to recognize these NFLE clinical features

Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome

Flavonoids are a subclass of polyphenols which are attractive, due to possessing various physiological activities, including a radioprotective effect. Tumor suppressor p53 is a primary regulator in the radiation response and is involved in the pathogenesis of radiation injuries. In this study, we revealed that isorhamnetin inhibited radiation cell death, and investigated its action mechanism focusing on DNA damage response. Although isorhamnetin moderated p53 activity, it promoted phosphorylation of ataxia telangiectasia mutated (ATM) and enhanced 53BP1 recruitment in irradiated cells. The radioprotective effect of isorhamnetin was not observed in the presence of ATM inhibitor, indicating that its protective effect was dependent on ATM. Furthermore, isorhamnetin-treated mice survived gastrointestinal death caused by a lethal dose of abdominal irradiation. These findings suggested that isorhamnetin enhances the ATM-dependent DNA repair process, which is presumably associated with the suppressive effect against GI syndrome

Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice

The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 +/- 8.12% vs. 23.26 +/- 10.02%, p 0.05) nor the difference in the sperm vitality rate (72.83 +/- 1.55% vs. 72.50 +/- 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice