The Mechanisms of Telomere and Telomerase Regulation in Hematologic Malignancies

11518

The Mechanisms of Telomere and Telomerase Regulation in Hematologic Malignancies

11518

The biosynthetic pathway of potato solanidanes diverged from that of spirosolanes due to evolution of a dioxygenase

ジャガイモの毒α-ソラニンはトマトの苦味成分から分岐進化したことを解明. 京都大学プレスリリース. 2021-03-03.Potato (Solanum tuberosum), a worldwide major food crop, produces the toxic, bitter tasting solanidane glycoalkaloids α-solanine and α-chaconine. Controlling levels of glycoalkaloids is an important focus on potato breeding. Tomato (Solanum lycopersicum) contains a bitter spirosolane glycoalkaloid, α-tomatine. These glycoalkaloids are biosynthesized from cholesterol via a partly common pathway, although the mechanisms giving rise to the structural differences between solanidane and spirosolane remained elusive. Here we identify a 2-oxoglutarate dependent dioxygenase, designated as DPS (Dioxygenase for Potato Solanidane synthesis), that is a key enzyme for solanidane glycoalkaloid biosynthesis in potato. DPS catalyzes the ring-rearrangement from spirosolane to solanidane via C-16 hydroxylation. Evolutionary divergence of spirosolane-metabolizing dioxygenases contributes to the emergence of toxic solanidane glycoalkaloids in potato and the chemical diversity in Solanaceae

Clinical Studies on Widespread Discoid Lupus Erythematosus

To clarify the relationship between discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE), we have studied clinically 15 patients with widespread DLE. The patients were divided into four grades according to the extent of their cutaneous lesions. Thirteen of 15 patients had widespread chronic discoid lesions as their initial manifestation. The ratio of females to males was approximately 1 : 1. The average age at onset was 39 yerars old, and the most common age was between 20 and 40 years. In four of five patients (all in Grade IV and men), the cutaneous lesions appeared after the age of 40 years. In many patients with widespread DLE, clinical and laboratory abnormalities were observed, such as fever, arthralgia, fatigability, photosensitivity, leucopenia, elevated erythrocyte sedimentation rate, hypergammaglobulinemia, proteinuria, but the incidence of LE cells, positive LE test, chronic BFP was much less in widespread DLE than SLE. Two patients (Grade IV) fulfilled the ARA criteria for SLE. These findings suggest that DLE and SLE are closely related diseases

愛媛県青島方言のアクセント

日本学術振興会愛媛大学大学院JSPSEhime University愛媛県喜多郡長浜町青島の方言アクセントについて,音調型,アクセント体系,類別体系の順に報告するとともに,特徴的な現象について分析し解釈を試みる。はじめに,音調型について,主として上昇の仕方の特徴と,語の持つ低接性に着目して記述する。次に,「内輪式」に近い体系であることを示す。そして,この島のアクセントが「内輪式」に近いことは,この付近のアクセント分布から見て極めて孤立的であることを言う。また,音調型などの体系の周辺部分に,「中央式」諸方言や近畿方言の一部に報告されている特徴にも共通する点があることを示した上で,この方言アクセントは,青島が,江戸の昔,播州坂越の人々により開かれた島だという史実を反映するものであり,現在の坂越方言アクセントと祖形を同じくする「中央式」の体系から,島という隔離された環境の中で「内輪式」の体系へと独自に変化してきたことを示すものであろうとの仮説を立てる。In this paper we focus on the dialect accent peculiar to Aoshima, a part of Nagahama Town, Ehime Prefecture. First, we illustrate the character of tone, especially, rising-tone and falling-tone observed between sentence fragments. Second, we show the accent system of Aoshima dialect, indicating that the accent dialect belongs to what is called the Nairin-type, in which the accent of tow-mora words shows "1. /2. 3. /4. 5." and one-mora words shows "1. /2. 3." We further show that, in peripheral parts of the system (e. g. low connecting character and vocabulary type), Aoshima accent shares the property of Chuou-type, in which the accent of two-mora words shows "1. /2. 3. /4. /5.", one-mora words shows "1. /2. /3." and having two resisters which we call Kooki-shiki and Teiki-shiki. Finely, we assume that the change of the accent in Aoshima from the Chuou-type to the Nairin-type is closely related with historical evidence that an immigration occurred from Sakoshi to Aoshima

Direct conversion of carlactonoic acid to orobanchol by cytochrome P450 CYP722C in strigolactone biosynthesis

Strigolactones (SLs) are carotenoid-derived phytohormones and rhizosphere signaling molecules for arbuscular mycorrhizal fungi and root parasitic weeds. Why and how plants produce diverse SLs are unknown. Here, cytochrome P450 CYP722C is identified as a key enzyme that catalyzes the reaction of BC-ring closure leading to orobanchol, the most prevalent canonical SL. The direct conversion of carlactonoic acid to orobanchol without passing through 4-deoxyorobanchol is catalyzed by the recombinant enzyme. By knocking out the gene in tomato plants, orobanchol was undetectable in the root exudates, whereas the architecture of the knockout and wild-type plants was comparable. These findings add to our understanding of the function of the diverse SLs in plants and suggest the potential of these compounds to generate crops with greater resistance to infection by noxious root parasitic weeds

Changes of behavior and consciousness in COVID-19

新型コロナウイルスの感染症の拡大と長期化に伴い，世の中はパンデミック状態にある一方でテレワークの普及によって，個人生活にとってはメリットもあると考えられる．そこで現在の行動やコミュニケーション等の意識の変化，さらにフレイルなど健康面の課題について①生活，行動と意識に関するアンケート，②通勤，勤務と行動と意識に関するアンケート2種類のWeb調査により実態を明らかにした．その結果，未知のウイルスに対する脅威感から，人々の意識やライフスタイルも大きく変容していて，在宅時間の増加によりメリットもある一方で，時間の使い方は自己への投資などには回っておらず，健康面では不安を抱えていることが明らかになり，フレイル等により健康寿命の短縮が危惧されるなど，新たな日常スタイルに向けての課題があることが明らかになった．With the spread and prolongation of the new coronavirus infection, the world is in a pandemic state, but the spread of telework is thought to have benefits for personal life. Therefore, awareness of current behavior and communication, etc. Regarding changes and health issues such as frailty, (1) questionnaires on life, behavior and consciousness, and (2) questionnaires on commuting work and behavior and consciousness, the actual situation was clarified by two types of Web surveys. As a result, people's consciousness and lifestyle have changed significantly due to the threat of unknown viruses, and while there are benefits to increasing the time spent at home, spending time is not used for self-investment. However, it became clear that he was worried about his health, and that there were issues for a new daily style, such as fear of shortening healthy life expectancy due to frailty syndrome

Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5

Sox9 is a transcription factor of the SRY family required for several steps of chondrogenesis. It activates the expression of various chondrocyte-specific genes, but the mechanisms and role of cofactors involved in Sox9-regulated gene transcription are not fully understood. Here, we report on the characterization of a Tat interactive protein-60 (Tip60) as Sox9-associated protein identified in a yeast two-hybrid screen. Both in vitro and in vivo assays confirmed the specificity of interactions between Sox9 and Tip60 including the existence of an endogenous complex containing both polypeptides in chondrocytes. Gel shift assays showed the presence of a complex containing Sox9, Tip60 and the DNA of an enhancer region of the Col2a1 promoter. Reporter assays using a Col2a1 promoter with multimerized Col2a1 Sox9-binding sites indicated that Tip60 enhanced the transcriptional activity of Sox9. A larger Col2a1 promoter showed that Tip60 increased the activity of this promoter in the presence of both Sox9 and Sox5. Ectopic expression of Sox9 and transient-cotransfection with Tip60 in COS7 cells showed a more diffuse subnuclear colocalization, suggesting changes in the chromatin structure. Chromatin immunoprecipitation assays showed that Tip60, Sox9 and Sox5 associated with the same Col2a1 enhancer region. Consistent with a role of Tip60 in chondrogenesis, addition of Tip60 siRNA to limb-bud micromass cultures delayed chondrocyte differention. Tip60 enhances acetylation of Sox9 mainly through K61, 253, 398 residues; however, the K61/253/398A mutant of Sox9 still exhibited enhanced transcriptional activity by Tip60. Our results support the hypothesis that Tip60 is a coactivator of Sox9 in chondrocytes

Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.

横紋筋肉腫におけるゲノム・エピゲノム異常の全体図を解明 -横紋筋肉腫を4群に分類-. 京都大学プレスリリース. 2015-07-03.Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS