HUNK Phosphorylates Rubicon to Support Autophagy

Background: Autophagy is a catabolic cellular recycling pathway that is essential for maintaining intracellular homeostasis. Autophagosome formation is achieved via the coordination of the Beclin-1 protein complex. Rubicon is a Beclin-1 associated protein that suppresses autophagy by impairing the activity of the class III PI3K, Vps34. However, very little is known about the molecular mechanisms that regulate Rubicon function. Methods: In this study, co-immunoprecipitation and kinase assays were used to investigate the ability of Hormonally Upregulated Neu-associated Kinase (HUNK) to bind to and phosphorylate Rubicon. LC3B was monitored by immunofluorescence and immunoblotting to determine whether phosphorylation of Rubicon by HUNK controls the autophagy suppressive function of Rubicon. Results: Findings from this study identify Rubicon as a novel substrate of HUNK and show that phosphorylation of Rubicon inhibits its function, promoting autophagy

Electrostatic Tuning of the Superconductor-Insulator Transition in Two Dimensions

Superconductivity has been induced in insulating ultra-thin films of amorphous bismuth using the electric field effect. The screening of electron-electron interaction was found to increase with electron concentration in a manner correlated with the tendency towards superconductivity. This does not preclude an increase in the density of states being important in the development of superconductivity. The superconductor-insulator transition appears to belong to the universality class of the three dimensional XY model.Comment: Four pages, three figures. Revised slightly to reflect referees' comment

Low-Temperature Glassy Response of Ultrathin Manganite Films to Electric and Magnetic Fields

The glassy response of thin films of La0.8Ca0.2MnO3 to external magnetic and gated electrostatic fields in a field-effect geometry has been studied at low temperatures. A hierarchical response with irreversible memory effects, non-ergodic time evolution, aging and annealing behavior of the resistance suggest that the dynamics are governed by strain relaxation for both electronic and magnetic perturbations. Cross-coupling of charge, spin, and strain have been exploited to tune the coercivity of an ultrathin manganite film by electrostatic gating.Comment: 4 pages, 5 figure

Introduction of human SOS physiological functions-Suggestions for resolving problems due to radiation exposure at low doses

ストレス社会対応の新しい教室を15年間主宰すべく,次の基本理念の基,研究と教育およびアウトリーチ活動を行いました。即ち,「科学における創造とは,未知のものを既知化し,非常識のものを常識化する」という作業です。具体的には,私共の創造作業とは,突然変異という従来の概念を「変異には必然性有り」とする考えへと変更させるものでした。この変異の発生を調節するメカニズムの解明は,生命研究の根源的課題であります。SOS応答という基本概念での研究ストラテジーでした。但し,多くの工夫が必要でした。まずは,約20年間をかけて,培養ヒト細胞レベルとヒト個体レベルで,変異発生に関わるストレス状態に超高感度で反応する実験システムを構築しました。次に,約15年間をかけて,どのようなストレス状態が変異発生の調節,ひいてはヒトの健康長寿に最適かという難問を解き明かそうとしました。宇宙旅行時代となりつつある現代,果して,ヒトは地球圏外のストレスにも耐えられるのでしょうか。そのような疑問にも答えようとしました。言うなれば,ヒトの将来を見越す進化医学という新しい学問分野を切り開こうとしたのです。 以上のような活動の基盤としては,約35年以前にさかのぼりますが,大腸菌におけるSOS応答の実証に成功したこと,およびそのことにつながる医学生と研究生としての学究活動とがありました。SOS応答とは,モールス信号のSOSにちなんでつけられた生命の危機管理応答です。そのような仕組みを演繹することにより,危機管理医学という新しい社会学問体系も創造し,その実践利用もすることとしました。従って,「1 発見から無限の貢献」を目標に,毎年わずか20数名の構成員からなる教室でしたが,多種多様な学際的創造過程での成果の社会還元にも努力しました。例えば,全国各地で官民の協力も得て,食品や環境の問題と関連させた様々な市民講座を開催しました。テロ対策上の社会ネットワーク作りもしました。言うなれば,学問の創造から新しい社会コミュニティー作りの実践への展開でした。なお,そのような講座での成果を教育現場へも還元しました。PST( Practical Self Training)と命名して,学生自らに社会の問題を発掘させ,その問題の解決を目指させるという能動型カリキュラムを構築してきました。知恵ではなく知識や実利を重視し数値化することに終始しがちな現代社会の要求にも対処した教室としての活動でした

Reciprocal regulation of PKA and rac signaling

Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of distinct GPCRs. A-kinase anchoring proteins tether PKA to specific intracellular sites to ensure precision and directionality of PKA phosphorylation events. Here, we show that the Rho-GTPase Rac contains A-kinase anchoring protein properties and forms a dynamic cellular protein complex with PKA. The formation of this transient core complex depends on binary interactions with PKA subunits, cAMP levels and cellular GTP-loading accounting for bidirectional consequences on PKA and Rac downstream signaling. We show that GTP-Rac stabilizes the inactive PKA holoenzyme. However, β-adrenergic receptor-mediated activation of GTP-Rac–bound PKA routes signals to the Raf-Mek-Erk cascade, which is critically implicated in cell proliferation. We describe a further mechanism of how cAMP enhances nuclear Erk1/2 signaling: It emanates from transphosphorylation of p21-activated kinases in their evolutionary conserved kinase-activation loop through GTP-Rac compartmentalized PKA activities. Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA–boosted activation of Raf-Mek-Erk. Consequently GTP-Rac functions as a dual kinase-tuning scaffold that favors the PKA holoenzyme and contributes to potentiate Erk1/2 signaling. Our findings offer additional mechanistic insights how β-adrenergic receptor-controlled PKA activities enhance GTP-Rac–mediated activation of nuclear Erk1/2 signaling

Susan Virginia Eblen\u27s Scrapbook 1942-1943

Susan Virginia Eblenhttps://repository.belmont.edu/scrapbooks/1021/thumbnail.jp

A Correlation Study of the a-b Ridge Breadth to Selected Bodily Dimensions

The correlation of the a-b ridge breadth to 12 anthropometric measurements was investigated in this study. The two samples used were 165 Armenians residing in Australia and 100 American Caucasians. Results of the analysis indicated that the a-b ridge breadth is correlated to seven specific body measurements. In order of decreasing correlation, they were wrist breadth, weight, stature, bicondylar femur, upper arm circumference, biacromial diameter, and calf circumference. It was also evident that bone was the only body size component that was correlated to the a-b ridge breadth