1,721,067 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Significance of proteasome dysfunction in the development of obesity-mediated hepatic insulin resistance
Full text link近年、肥満は小胞体(ER)ストレスを惹起することで肝臓および脂肪組織にインスリン抵抗性を誘導することが示された。本研究では、肥満がいかにERストレスを誘導するかの分子メカニズムを解明した。肥満状態の肝臓ではプロテアソーム(PS)活性が低下し、ポリユビキチン化蛋白質が蓄積した。このPS機能異常は、異常蛋白質の蓄積に起因するERストレスを誘導し、JNK活性化を介して肝にインスリン抵抗性を惹起した。これとは独立して、PS機能障害はFoxO1分解を抑制して肝糖新生を促進した。さらにPS機能障害によるタンパク分解抑制とERストレスの惹起がSREBP-1cを活性化して直接的に肝を脂肪化した。Chronic endoplasmic reticulum (ER) stress is a major contributor to obesity-induced insulin resistance in the liver. Here, we investigated the molecular link between obesity and ER stress. Mouse models of obesity and diabetes and proteasome activator 28 (PA28)-null mice showed 30-40% reduction in proteasome activity and accumulation of poly-ubiquitinated proteins in the liver. PA28-null mice also showed hepatic steatosis, decreased hepatic insulin signaling, and increased hepatic glucose production. The link between proteasome dysfunction and hepatic insulin resistance involves ER stress leading to hyperactivation of c-Jun N-terminal kinase and forkhead box O1 (FoxO1) activation in the liver. Taken together, our data suggest that proteasome dysfunction mediates obesity-induced ER stress, leading to insulin resistance in the liver.研究課題/領域番号:23591301, 研究期間(年度):2011-2013出典：研究課題「肥満による肝インスリン抵抗性形成におけるプロテアソーム機能異常の意義」課題番号:23591301
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-23591301/23591301seika/)を加工して作成金沢大学医薬保健研究域医学系research repor
Metabolic pathway altered in the liver of patients with type 2 diabetes and its regulation
Full text link本研究では、2型糖尿病患者の肝臓で発現変動する遺伝子および代謝パスウェイを抽出し、それらの病態生理学的意義を遺伝子発現-臨床連関から明らかにするとともに,代謝パスウェイの協調的発現制御機構解明を試みた。
1)2型糖尿病患者および健常者の肝に発現する遺伝子のSAGE解析およびDNAチップ解析:糖尿病肝および正常肝の間で差異のある遺伝子と代謝パスウェイを抽出した。
2)病態形成分泌タンパク候補遺伝子の抽出:SAGEおよびDNAチップ解析で抽出した機能未解明の分泌蛋白コード遺伝子のうち、BMI、インスリン抵抗性、血糖コントロールなどの病態と発現量が関連している遺伝子を同定し、特許出願した(出願番号2005-125689)。
3)代謝パスウェイの抽出:2型糖尿病の肝臓ではミトコンドリア酸化的リン酸化に関与するOXPHOS遺伝子が協調的に発現亢進していることを明らかにした。
4)肝臓におけるOXPHOS遺伝子群の病態生理学的意義の解明:OXPHOS遺伝子群各遺伝子の標準化スコア平均値をOXPHOS mean centroid として算出し,2型糖尿病の病態との関連を検索した.その結果OXPHOS mean centroidは空腹時血糖値およびインスリン抵抗性指数と相関した。5)肝臓におけるOXPHOS遺伝子群の協調的発現を制御する病態・因子:肝発現遺伝子相互の関連を解析したところ、OXPHOS mean centroidは糖新生関連遺伝子群、活性酸素産生系およびredox系遺伝子群と有意に正相関した。したがって、糖尿病患者の肝臓では、糖代謝・脂質代謝の結果生じる基質の過剰供給によりOXPHOSおよび活性酸素産生系遺伝子群が発現亢進し、酸化ストレスが生じて肝臓におけるインスリン抵抗性がもたらされる可能性がある。さらに、転写因子・転写補助因子の中でも、PPARG,ESRRA,NCOA1,THRA,NCOA2などのエネルギー代謝に関わる遺伝子と正相関した。これらの中に、肝と骨格筋における組織特異的OXPHOS遺伝子発現を制御する因子が存在する可能性がある。Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes for OXPHOS have been reported to be down-regulated in the skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown.
In the present study, I analyzed gene expression for OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with normal glucose tolerance (NGT) using serial analysis of gene expression (SAGE) and DNA chip analysis. I evaluated the correlation between gene expression levels for OXPHOS and clinical parameters of individuals with type 2 diabetes and NGT.
Both gene analyses showed that genes for OXPHOS were significantly up-regulated in the type 2 diabetic liver.
In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that rRNAs were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that gene expression for OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-a (ERR-α) or peroxisome proliferator-activated receptor-y (PPAR-y), was a predictor of fasting plasma glucose levels, independent of age, body mass index, insulin resistance, and fasting insulin levels (P=0.04). Surprisingly, genes for OXPHOS did not correlate with either peroxisome proliferator-activated receptor-γ coactivator-la (PGC-1α) or nuclear respiratory factor 1 (NRF-1).
These results indicate that up-regulated genes for OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, are associated with fasting hyperglycemia in patients with type 2 diabetes.研究課題/領域番号:17590920, 研究期間(年度):2005-2006出典：「2型糖尿病患者の肝臓における酸化的リン酸化を制御するマスター遺伝子の同定」研究成果報告書 課題番号17590920
(KAKEN：科学研究費助成事業データベース（国立情報学研究所）)
本文データは著者版報告書より作成research repor
Roles of intracellular proteolytic systems in maintaining energy metabolism homeostasis
Full text link本研究では、細胞内の蛋白分解系のエネルギー代謝恒常性維持における役割の統合的理解を目指し、次の3つの未解決課題に取り組んだ。①肥満状態でプロテアソーム機能が低下する機序、②プロテアソーム活性阻害下および飢餓状態での代償的オートファジーのエネルギー代謝における意義とその基質、③骨格筋におけるプロテアソーム機能障害のインスリン感受性における意義To understand the roles of intracellular proteolytic systems in maintaining energy metabolism homeostasis, the present study addressed the following three unresolved issues. ①Mechanisms underlying proteasome dysfunction in obesity, ②Significance of compensatory autophagy and its substrates under inhibition of proteasome activity and starvation, ③Significance of proteasome dysfunction in skeletal muscle in insulin sensitivity.研究課題/領域番号:26461329, 研究期間(年度):2014-04-01 - 2017-03-31出典：「細胞内蛋白分解系のエネルギー代謝恒常性維持における統合的役割の解明」研究成果報告書 課題番号26461329
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26461329/26461329seika/）を加工して作成金沢大学医薬保健研究域医学系research repor
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Identification of a novel hepatokine that causes insulin resistance and diabetic vascular complications
Full text linkヒト肝臓での発現がインスリン抵抗性および高血糖と関連する機能性ヘパトカインとしてセレノプロテインP(selenoprotein P ; SeP)を同定した。SePは主に肝臓で産生される分子量約50キロダルトンの分泌タンパクで、必須微量元素であるセレンの輸送タンパク、およびグルタチオンの酸化を介した抗酸化タンパクとして機能する。in vitroおよびin vivoの検討から、SePは、少なくとも一部にAMPキナーゼの活性抑制を介して全身のインスリン抵抗性を引き起こし、糖代謝を障害することがわかった。We identified a gene encoding selenoprotein P (SeP), the hepatic expression levels of which were positively correlated with insulin resistance and hyperglycemia in patients with type 2 diabetes. SeP caused insulin resistance, at least partly, by inactivating AMPK both in vitro and in vivo.出典：研究課題「インスリン抵抗性と血管合併症を形成する肝臓由来新規ホルモンの機能解析」課題番号20591054
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-20591054/20591054seika/）を加工して作成金沢大学医薬保健研究域医学系research repor
Perturbation of redox balance in pathophysiology of diabetes
Full text linkVarious antioxidant drugs have been clinically applied to reduce oxidative stress, but none have achieved sufficient therapeutic efficacy. Selenoprotein P (SeP) is a hepatokine, a bioactive molecule derived from the liver, which plays roles in the pathogenesis of type 2 diabetes. In the present study, we show that SeP is an endogenous factor that induces signal transduction via eliminating physiological reactive oxygen species. Such SeP-mediated reductive stress caused diabetic pathology in the brown adipose tissue and bone. These findings suggest that SeP is a potential novel therapeutic target against diabetic complications.酸化ストレスの軽減を目的として種々の抗酸化薬が臨床応用されているが、十分な治療効果を上げているものはない。セレノプロテインP (SeP)は2型糖尿病の病態を形成する肝臓由来生理活性分子、ヘパトカインである。本研究では、SePが褐色脂肪組織および骨において、還元ストレスを誘発する内因性因子として、生理的活性酸素種を消去することにより、シグナル伝達抵抗性、および糖尿病病態を形成することを示した。これらの知見は、SePが糖尿病の合併症に対する新規治療標的となり得ることを示唆する。研究課題/領域番号:17H04199, 研究期間(年度):2017-04-01 - 2022-03-31出典：研究課題「酸化・還元バランスの破綻による糖尿病病態形成機構の解明」課題番号17H04199
（KAKEN：科学研究費助成事業データベース（国立情報学研究所））
（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-17H04199/17H04199seika/）を加工して作成金沢大学医薬保健研究域医学系research repor
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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