p53 変異型ヒト口腔がん細胞における高LET 放射線によるp53 非依存Akt 生存シグナルの抑制

Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G(2)/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp53 bearing cancer cells.博士（医学）・甲第598号・平成25年3月15日Copyright © 2012 Elsevier Inc. All rights reserve

Variation in bradyrhizobial NopP effector determines symbiotic incompatibility with Rj2-soybeans via effector-triggered immunity

The soybean Rj2 gene encodes a TIR-NBS-LRR protein that confers resistance to nodulation by certain rhizobial strains. Here, the authors show that T3SS effector NopP is an avirulence protein that is necessary for Bradyrhizobium diazoefficiens USDA 122 to trigger Rj2-dependent incompatibility

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

On the New Antarctic Research Ship FUJI

本年から南極観測が再開されることに決まり,「宗谷」の代船として南極観測船「ふじ」が建造されることになった.「ふじ」は日本最初の本格的極地用砕氷船であって,南極における輸送,砕氷,観測の任務に従事するものである.船の寸法,船型等は主として砕氷船としての性能から決められ,それに大型ヘリコプター3機を搭載して大きな空輸能力を有することが特徴である.推進機関はディーゼル電気推進方式を採用し,氷海中での行動能力の増大を狙っている.長期行動に備え居住性向上には特に意を用い,更に,減揺タンクを設けて航行中の船上作業に便ならしめている.船体構造は氷圧力に対し極めて強固に設計された.船上観測設備は11科学部門に渉っている

シン ナンキョク カンソクセン フジ ニツイテ

本年から南極観測が再開されることに決まり,「宗谷」の代船として南極観測船「ふじ」が建造されることになった.「ふじ」は日本最初の本格的極地用砕氷船であって,南極における輸送,砕氷,観測の任務に従事するものである.船の寸法,船型等は主として砕氷船としての性能から決められ,それに大型ヘリコプター3機を搭載して大きな空輸能力を有することが特徴である.推進機関はディーゼル電気推進方式を採用し,氷海中での行動能力の増大を狙っている.長期行動に備え居住性向上には特に意を用い,更に,減揺タンクを設けて航行中の船上作業に便ならしめている.船体構造は氷圧力に対し極めて強固に設計された.船上観測設備は11科学部門に渉っている