the-use-of-chemostats-in-microbial-systems-biology

The Use of Chemostats in Microbial Systems Biology

Cells regulate their rate of growth in response to signals from the external world. As the cell grows, diverse cellular processes must be coordinated ...

New York University 

Previous studies have demonstrated the benefits of music therapy in Alzheimer's patients, focusing either on improvement of healthy cognitive and social skills, or reduction of agitation symptoms. The present study examined the effect of background music on both positive and negative behaviors, during a time in which patients were not occupied with any structured activity. Twenty eight participants were observed both with and without stimulative, familiar background music. Results showed both a significant increase in positive social behaviors and a significant decrease in negative behaviors related to agitation when music is played. Results demonstrate the contribution of music to enhancing general positive functioning in elderly patients with dementia, and reducing negative behaviors typical of their condition.

The effect of background stimulative music on behavior in Alzheimer's patients.

A large percentage of older people suffer from chronic insomnia, affecting many aspects of life quality and well-being. Although insomnia is most often treated with medication, a growing number of studies demonstrate the efficiency of various relaxation techniques. The present study had three aims: first, to compare two relaxation techniques--music relaxation and progressive muscular relaxation--on various objective and subjective measures of sleep quality; second, to examine the effect of these techniques on anxiety and depression; and finally, to explore possible relationships between the efficiency of both techniques and personality variables. Fifteen older adults took part in the study. Following one week of base-line measurements of sleep quality, participants followed one week of music relaxation and one week of progressive muscular relaxation before going to sleep. Order of relaxation techniques was controlled. Results show music relaxation was more efficient in improving sleep. Sleep efficiency was higher after music relaxation than after progressive muscular relaxation. Moreover, anxiety was lower after music relaxation. Progressive muscular relaxation was related to deterioration of sleep quality on subjective measures. Beyond differences between the relaxation techniques, extraverts seemed to benefit more from both music and progressive muscular relaxation. The advantage of non-pharmacological means to treat insomnia, and the importance of taking individual differences into account are discussed.

The effect of music relaxation versus progressive muscular relaxation on insomnia in older people and their relationship to personality traits.

&#x7F51;&#x683C;&#x86CB;&#x767D;&#x819C;&#x548C;&#x5176;&#x7EC4;&#x88C5;&#x6210;&#x6D82;&#x5C42;&#x5751;&#x7684;&#x62DB;&#x8058;&#x7ED3;&#x679C;&#x4E0E;&#x541E;&#x9002;&#x914D;&#x5668;&#x548C;&#x5176;&#x4ED6;&#x8C03;&#x8282;&#x86CB;&#x767D;&#x5728;&#x7279;&#x5B9A;&#x8102;&#x8D28;&#x5FAE;&#x73AF;&#x5883;&#x7684;&#x4E0A;&#x4E0B;&#x6587;&#x4E2D;&#x7684;&#x4E92;&#x52A8;&#x3002;Dab2 &#xFF08;&#x7981;&#x7528; 2&#xFF09; &#x662F;&#x6709;&#x4E1D;&#x5206;&#x88C2;&#x7684;&#x78F7;&#x86CB;&#x767D;&#x548C;&#x5355;&#x4F53;&#x9002;&#x914D;&#x5668;&#x4E3A;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x4ECB;&#x5BFC;&#x7684;&#x5185;&#x541E;&#x4F5C;&#x7528;&#x3002;&#x5728;&#x672C;&#x7814;&#x7A76;&#x4E2D;&#xFF0C;&#x6211;&#x4EEC;&#x91C7;&#x7528; GFP (&#x7EFF;&#x8272;&#x8367;&#x5149;&#x86CB;&#x767D;) &#x878D;&#x5408;&#x6784;&#x9020;&#x7684;&#x4E0D;&#x540C;&#x4E9A;&#x578B;&#x548C;&#x7A81;&#x53D8;&#x4F53;&#x7684;&#x5927;&#x9F20; Dab2 &#x548C;&#x7279;&#x70B9;&#x53CA;&#x5176;&#x5BF9;&#x5927;&#x5C0F;&#x3001; &#x5206;&#x5E03;&#x548C;&#x52A8;&#x6001;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x7684;&#x7A0B;&#x5E8F;&#x96C6;&#x7684;&#x5F71;&#x54CD;&#x3002;&#x589E;&#x5F3A;&#x7684; p82 &#x5F02;&#x6784;&#x4F53;&#x7684; Dab2 &#x5728; COS7 &#x7EC6;&#x80DE;&#x4E2D;&#x7684;&#x8868;&#x8FBE;&#x6C34;&#x5E73;&#x6269;&#x5927;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x5728;&#x7EC6;&#x80DE;&#x8D28;&#x819C;&#x7684;&#x7A0B;&#x5E8F;&#x96C6;&#x3002;p82-&#x7F51;&#x683C;&#x86CB;&#x767D;&#x7684;&#x7A0B;&#x5E8F;&#x96C6;&#xFF0C;&#x96C6;&#x4E2D;&#x9644;&#x52A0;&#x541E;&#x86CB;&#x767D;&#x8D28;&#xFF0C;&#x5982; AP2 &#xFF08;&#x9002;&#x914D;&#x5668;&#x86CB;&#x767D; 2&#xFF09; &#x548C; epsin&#xFF0C;&#x662F;&#x5728;&#x54EA;&#x4E2A; p82 &#x548C;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x4EA4;&#x6D41;&#x79EF;&#x6781;&#x819C;&#x7ED1;&#x5B9A;&#x548C;&#x80DE;&#x6D46;&#x9488;&#x5BF9;&#x52A8;&#x6001;&#x7ED3;&#x6784;&#x3002;P82 &#x80FD;&#x591F;&#x8BF1;&#x4F7F;&#x6269;&#x5927;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x7684;&#x7A0B;&#x5E8F;&#x96C6;&#x662F;&#x4F9D;&#x8D56;&#x529F;&#x80FD; PTB &#x57DF; &#xFF08;&#x916A;&#x6C28;&#x9178;&#x7ED1;&#x5B9A;&#x57DF;&#xFF09;&#xFF0C;&#x5BF9;&#x7ED1;&#x5B9A;&#x5230;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x548C;&#x78F7;&#x8102;&#xFF0C;&#x548C;&#x4E4B;&#x524D;&#x7684;&#x5BA2;&#x8FD0;&#x5927;&#x697C;&#x57DF;&#x7684;&#x65B0;&#x53D1;&#x73B0;&#x548C;&#x8FDB;&#x5316;&#x4FDD;&#x6301;&#x591A;&#x805A;&#x8D56;&#x6C28;&#x9178;&#x62C9;&#x4F38;&#x7684;&#x5B58;&#x5728;&#x3002;Dab2 &#x52A0;&#x5F3A;&#x4F20;&#x64AD; COS7 &#x7EC6;&#x80DE;&#x7EA4;&#x7EF4;&#x8FDE;&#x63A5;&#x86CB;&#x767D;&#x5BF9;&#x9700;&#x8981;&#x8FD9;&#x4E9B;&#x76F8;&#x540C;&#x7684;&#x5206;&#x5B50;&#x529F;&#x80FD;&#x3002;Dab2 p82 &#x9F3B;&#x606F;&#x8089;&#x7684;&#x80FD;&#x529B;&#x589E;&#x5F3A;&#x7EC6;&#x80DE;&#x94FA;&#x5C55;&#x8BC1;&#x5B9E;&#x5728; HeLa &#x7EC6;&#x80DE;&#x548C;&#x7EC6;&#x80DE; HBL (&#x4EBA;&#x7C7B;&#x4E73;&#x817A;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;)&#x3002;COS7 &#x7EC6;&#x80DE;&#x8868;&#x8FBE;&#x7EFF;&#x8272;&#x8367;&#x5149;&#x86CB;&#x767D;&#x57FA;&#x56E0; p82 &#x548C;&#x7EA4;&#x7EF4;&#x8FDE;&#x63A5;&#x86CB;&#x767D;&#x6D53;&#x7F29;&#x5230;&#x9540; beta1 &#x6574;&#x5408;&#x6210;&#x7F51;&#x683C;&#x86CB;&#x767D; p82 &#x7A0B;&#x5E8F;&#x96C6;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x5728;&#x5355;&#x5143;&#x683C;&#x5728;&#x8513;&#x5EF6;&#xFF0C;p82-&#x7F51;&#x683C;&#x86CB;&#x767D;&#x7684;&#x7A0B;&#x5E8F;&#x96C6;&#x96C6;&#x4E2D;&#x5728;&#x7AD9;&#x70B9;&#x7684;&#x521D;&#x59CB;&#x7EC6;&#x80DE;&#x57FA;&#x8D28;&#x8054;&#x7CFB;&#x4EBA;&#x6709;&#x7F3A;&#x5E2D;&#x53CA;&#x6765;&#x81EA;&#x533A;&#x57DF;&#x7684;&#x6FC0;&#x70C8;&#x819C;&#x539A;&#x9053;&#x3002;&#x6211;&#x4EEC;&#x5EFA;&#x8BAE;&#x628A; Dab2 &#x548C;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x6574;&#x5408;&#x7D20;&#x4ECB;&#x5BFC;&#x7684;&#x7EC6;&#x80DE;&#x4F20;&#x64AD;&#x4F5C;&#x7528;&#x3002;

Dab2 &#x89C4;&#x5B9A;&#x4E86;&#x7F51;&#x683C;&#x86CB;&#x767D;&#x5927;&#x4F1A;&#x548C;&#x7EC6;&#x80DE;&#x8513;&#x5EF6;&#x3002;

The recruitment of clathrin to the membrane and its assembly into coated pits results from its interaction with endocytic adaptors and other regulatory proteins in the context of a specific lipid microenvironment. Dab2 (disabled 2) is a mitotic phosphoprotein and a monomeric adaptor for clathrin-mediated endocytosis. In the present study, we employed GFP (green fluorescent protein) fusion constructs of different isoforms and mutants of rat Dab2 and characterized their effect on the size, distribution and dynamics of clathrin assemblies. Enhanced levels of expression of the p82 isoform of Dab2 in COS7 cells induced enlarged clathrin assemblies at the plasma membrane. p82-clathrin assemblies, which concentrate additional endocytic proteins, such as AP2 (adaptor protein 2) and epsin, are dynamic structures in which both p82 and clathrin exchange actively between the membrane-bound and cytosolic sub-populations. The ability of p82 to induce enlarged clathrin assemblies is dependent on the presence of a functional PTB domain (phosphotyrosine-binding domain), on binding to clathrin and phospholipids, and on a newly identified and evolutionarily conserved poly-lysine stretch which precedes the PTB domain. These same molecular features are required for Dab2 to enhance the spreading of COS7 cells on fibronectin. The ability of the p82 isoform of Dab2 to enhance cell spreading was confirmed in both HeLa cells and HBL cells (human breast epithelial cells). COS7 cells expressing GFP-p82 and plated on to fibronectin concentrate the beta1 integrin into clathrin-p82 assemblies. Furthermore, during cell spreading, p82-clathrin assemblies concentrate at the site of the initial cell-matrix contact and are absent from regions of intense membrane ruffling. We propose a role for Dab2 and clathrin in integrin-mediated cell spreading.

Dab2 regulates clathrin assembly and cell spreading.

Le recrutement de clathrine &agrave; la membrane et son Assembl&eacute;e en puits recouverts r&eacute;sulte de son interaction avec les adaptateurs endocytose et autres prot&eacute;ines r&eacute;gulatrices dans le contexte d&#39;un micro-environnement de lipides sp&eacute;cifiques. Dab2 (d&eacute;sactiv&eacute; 2) est une phosphoprot&eacute;ine mitotique et un adaptateur monom&egrave;re d&#39;endocytose clathrine. Dans la pr&eacute;sente &eacute;tude, nous avons employ&eacute; des constructions de fusion de GFP (green fluorescent protein) des diff&eacute;rentes isoformes et mutants de rat Dab2 et caract&eacute;ris&eacute; leur effet sur la taille, la distribution et la dynamique des assemblages de clathrine. Am&eacute;liorer le niveau d&#39;expression de l&#39;isoforme p82 de Dab2 dans les cellules COS7 induites &eacute;largies clathrine assembl&eacute;es &agrave; la membrane plasmique. P82-clathrine assembl&eacute;es, qui concentrent les prot&eacute;ines intervenant dans l&#39;endocytose additionnelles, telles que AP2 (prot&eacute;ine adaptatrice 2) et epsin, sont des structures dynamiques dans lequel exchange p82 tant de clathrine activement entre les sous-populations membranaires et cytosoliques. La capacit&eacute; du p82 &agrave; induire des assemblages de clathrine &eacute;largie est d&eacute;pendante de la pr&eacute;sence d&#39;un domaine fonctionnel de PTB (domaine de liaison &agrave; phosphotyrosine), sur la liaison de clathrine et des phospholipides et sur un tron&ccedil;on de poly-lysine nouvellement identifi&eacute;s et &eacute;volutivement conserv&eacute;s qui pr&eacute;c&egrave;de le domaine de la PTB. Ces m&ecirc;mes caract&eacute;ristiques mol&eacute;culaires sont n&eacute;cessaires pour Dab2 am&eacute;liorer la diffusion des cellules COS7 sur fibronectine. La capacit&eacute; de l&#39;isoforme p82 de Dab2 afin d&#39;am&eacute;liorer la propagation de cellules a &eacute;t&eacute; confirm&eacute;e dans les cellules HeLa et les cellules HBL (cellules &eacute;pith&eacute;liales mammaires humains). COS7 cellules exprimant GFP-p82 et plaqu&eacute; sur la fibronectine concentr&eacute; l&#39;int&eacute;grine beta1 dans des assemblys de clathrine-p82. En outre, au cours de la propagation de la cellule, p82-clathrine assembl&eacute;es se concentrent sur le site du contact cellule-matrice initiale et sont absentes des r&eacute;gions de membrane intense &eacute;bouriffer. Nous proposons un r&ocirc;le pour Dab2 et la clathrine dans la propagation de l&#39;int&eacute;grine cellulaire.

Dab2 r&eacute;gule la clathrine assemblage et la diffusion de la cellule.

Die Rekrutierung von Clathrin auf die Membran und die Assembly in beschichtete Gruben ergibt sich aus der Interaktion mit endocytic Adapter und anderen regulatorischen Proteine im Zusammenhang mit einer bestimmten Lipid-Untersuchungsverfahren. Dab2 (deaktiviert 2) ist eine mitotische Phosphoprotein und ein Monomer-Adapter f&uuml;r Clathrin-vermittelte Endozytose. In der vorliegenden Studie wir GFP (green fluorescent Protein) Verschmelzung Konstrukte der verschiedenen Isoformen und Mutanten Ratte Dab2 besch&auml;ftigt und gepr&auml;gt, deren Auswirkungen auf die Gr&ouml;&szlig;e, Verteilung und Dynamik der Clathrin-Assemblys. Erh&ouml;hte Niveaus der Ausdruck der p82-Isoform von Dab2 in COS7 Zellen induziert vergr&ouml;&szlig;ert Clathrin Assemblys an der Plasmamembran. P82-Clathrin-Assemblys, die zus&auml;tzliche endocytic Proteine wie AP2 konzentrieren (Adapterprotein 2) und Epsin, sind dynamische Strukturen, in welche p82 und Clathrin Exchange aktiv zwischen der Membrane-springen und Zytosolische Subpopulationen. Die F&auml;higkeit der p82, erweiterten Clathrin Assemblys induzieren h&auml;ngt das Vorhandensein einer funktionalen PTB Dom&auml;ne (Phosphotyrosine-Bindung), binden an Clathrin und Phospholipiden und eine neu identifizierte und evolution&auml;r konservierte Poly-Lysin-Strecke, die die PTB-Dom&auml;ne vorausgeht. Diese gleichen molekularen Eigenschaften sind f&uuml;r Dab2 zu verbessern, die Verbreitung der COS7 Zellen auf Fibronektin erforderlich. HeLa-Zellen und HBL Zellen (Epithelzellen der menschlichen Brust) best&auml;tigte die F&auml;higkeit der p82-Isoform von Dab2, Zelle, die Verbreitung zu erh&ouml;hen. COS7 Zellen auszudr&uuml;cken GFP-p82 / plattiert auf Fibronektin-Konzentrat die beta1-Integrin in Clathrin-p82 Assemblys. Dar&uuml;ber hinaus w&auml;hrend der Zelle verbreiten, p82-Clathrin Assemblys am Standort der urspr&uuml;nglichen Zelle-Matrix-Kontakt zu konzentrieren und Fehlen von Regionen der intensiven Membran halten muss. Wir schlagen eine Rolle f&uuml;r die Dab2 und Clathrin Integrin-vermittelte Zelle zu verbreiten.

Dab2 regelt Clathrin Montage- und Zelle zu verbreiten.

L&#39;assunzione di clatrina la membrana e relativo montaggio in pozzi rivestiti risultati dalla sua interazione con adattatori endocitico e altre proteine regolatorie nel contesto di un microambiente specifico dei lipidi. Dab2 (disabili 2) &egrave; una fosfoproteina mitotica e un adattatore monomerico per endocitosi Clatrina-mediata. Nel presente studio, abbiamo impiegato costrutti di fusione di GFP (green fluorescent protein) delle diverse isoforme e mutanti di topo Dab2 e caratterizzato il loro effetto sulla dimensione, distribuzione e dinamica della clatrina assembly. Maggiore livelli di espressione dell&#39;isoforma di Dab2 nelle cellule COS7 indotta p82 allargata Clatrina assembly alla membrana del plasma. P82-clatrina assembly, che si concentrano le proteine endocitico supplementari, come AP2 (proteina dell&#39;adattatore 2) ed epsin, sono strutture dinamiche in cui exchange sia p82 e clatrina attivamente tra le sottopopolazioni membrana-limiti e citosolici. La capacit&agrave; di indurre gli assembly clatrina allargata p82 &egrave; dipendente dalla presenza di un dominio PTB funzionale (phosphotyrosine binding domain), sull&#39;associazione di clatrina e fosfolipidi e su un tratto evolutivamente conservato e recentemente identificata poli-lisina che precede il dominio PTB. Queste caratteristiche molecolari sono richieste per Dab2 migliorare la diffusione delle cellule COS7 su fibronectina. La capacit&agrave; dell&#39;isoforma di Dab2 p82 per migliorare la diffusione delle cellule &egrave; stata confermata sia le cellule HeLa e HBL cellule (cellule epiteliali umane del seno). COS7 le cellule che esprimono GFP-p82 e placcato su fibronectina concentrato l&#39;integrina beta1 in assembly clatrina-p82. Inoltre, durante la diffusione delle cellule, p82-clatrina assembly concentrare presso il sito del contatto iniziale cellula-matrice e sono assenti dalle regioni della membrana intenso scompigliava. Vi proponiamo un ruolo per Dab2 e clatrina nella diffusione di integrina-mediata delle cellule.

Dab2 regola clatrina assieme e la diffusione delle cellule.

&#x30A8;&#x30F3;&#x30C9;&#x30B5;&#x30A4;&#x30C8;&#x30FC;&#x30B7;&#x30B9; &#x30A2;&#x30C0;&#x30D7;&#x30BF;&#x30FC;&#x3068;&#x4ED6;&#x8ABF;&#x7BC0;&#x86CB;&#x767D;&#x8CEA;&#x7279;&#x5B9A;&#x8102;&#x8CEA;&#x5FAE;&#x5C0F;&#x74B0;&#x5883;&#x306E;&#x30B3;&#x30F3;&#x30C6;&#x30AD;&#x30B9;&#x30C8;&#x3067;&#x306E;&#x5BFE;&#x8A71;&#x304B;&#x3089;&#x819C;&#x3068;&#x305D;&#x306E;&#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x306B;&#x88AB;&#x8986;&#x30D4;&#x30C3;&#x30C8;&#x3078;&#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3;&#x306E;&#x52DF;&#x96C6;&#x306E;&#x7D50;&#x679C;&#x3057;&#x307E;&#x3059;&#x3002;Dab2 (2 &#x7121;&#x52B9;) &#x6709;&#x7CF8;&#x5206;&#x88C2;&#x30EA;&#x30F3;&#x86CB;&#x767D;&#x8CEA;&#x3068;&#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3;&#x4ECB;&#x5728;&#x578B;&#x30A8;&#x30F3;&#x30C9;&#x30B5;&#x30A4;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x306E;&#x5358;&#x91CF;&#x4F53;&#x306E;&#x30A2;&#x30C0;&#x30D7;&#x30BF;&#x30FC;&#x306F;&#x3001;&#x3067;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x306F;, &#x7570;&#x306A;&#x308B;&#x30A2;&#x30A4;&#x30BD; &#x30D5;&#x30A9;&#x30FC;&#x30E0;&#x306E; GFP &#xFF08;&#x7DD1;&#x8272;&#x86CD;&#x5149;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#xFF09; &#x30D5;&#x30E5;&#x30FC;&#x30B8;&#x30E7;&#x30F3; &#x30B3;&#x30F3;&#x30B9;&#x30C8;&#x30E9;&#x30AF;&#x30C8;&#x3068;&#x5909;&#x7570;&#x30E9;&#x30C3;&#x30C8; Dab2 &#x306E;&#x63A1;&#x7528;&#x3001;&#x30B5;&#x30A4;&#x30BA;&#x3001;&#x5206;&#x5E03;&#x304A;&#x3088;&#x3073;&#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; &#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x306E;&#x52D5;&#x614B;&#x3078;&#x306E;&#x5F71;&#x97FF;&#x306E;&#x7279;&#x5FB4;&#x3057;&#x307E;&#x3059;&#x3002;&#x5F37;&#x5316;&#x3055;&#x308C;&#x305F; Dab2 &#x306B;&#x3088;&#x308B; COS7 &#x7D30;&#x80DE;&#x306E; p82 &#x30A2;&#x30A4;&#x30BD; &#x30D5;&#x30A9;&#x30FC;&#x30E0;&#x306E;&#x767A;&#x73FE;&#x30EC;&#x30D9;&#x30EB;&#x306F;&#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; &#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x539F;&#x5F62;&#x8CEA;&#x819C;&#x306B;&#x62E1;&#x5927;&#x3002;AP2 &#x306A;&#x3069;&#x306E;&#x8FFD;&#x52A0;&#x306E;&#x30A8;&#x30F3;&#x30C9;&#x30B5;&#x30A4;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x86CB;&#x767D;&#x8CEA;&#x3092;&#x96C6;&#x4E2D; p82 &#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; &#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA; (&#x30A2;&#x30C0;&#x30D7;&#x30BF;&#x30FC;&#x86CB;&#x767D;&#x8CEA; 2) &#x3068; epsin&#x3001;&#x3069;&#x306E; p82 &#x3068;&#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3;&#x306E;&#x4EA4;&#x63DB;&#x819C;&#x7D50;&#x5408;&#x3068;&#x7D30;&#x80DE;&#x8CEA;&#x306E;&#x30B5;&#x30D6;&#x96C6;&#x56E3;&#x9593;&#x306B;&#x7A4D;&#x6975;&#x7684;&#x306B;&#x30C0;&#x30A4;&#x30CA;&#x30DF;&#x30C3;&#x30AF;&#x306A;&#x69CB;&#x9020;&#x3067;&#x3059;&#x3002;P82 &#x62E1;&#x5927;&#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; &#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x8A98;&#x5C0E;&#x80FD;&#x6A5F;&#x80FD; PTB &#x30C9;&#x30E1;&#x30A4;&#x30F3; (&#x30DB;&#x30B9;&#x30DB;&#x30C1;&#x30ED;&#x30B7;&#x30F3;&#x7D50;&#x5408;&#x30C9;&#x30E1;&#x30A4;&#x30F3;) &#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3;&#x304A;&#x3088;&#x3073;&#x30EA;&#x30F3;&#x8102;&#x8CEA;&#x3078;&#x306E;&#x30D0;&#x30A4;&#x30F3;&#x30C9;&#x3067; PTB &#x30C9;&#x30E1;&#x30A4;&#x30F3;&#x306E;&#x524D;&#x306B;&#x65B0;&#x305F;&#x306B;&#x540C;&#x5B9A;&#x3055;&#x308C;&#x305F;&#x3068;&#x9032;&#x5316;&#x7684;&#x306B;&#x4FDD;&#x5B58;&#x3055;&#x308C;&#x305F;&#x30DD;&#x30EA; l-&#x30EA;&#x30B8;&#x30F3; &#x30B9;&#x30C8;&#x30EC;&#x30C3;&#x30C1;&#x4E0A;&#x306E;&#x5B58;&#x5728;&#x306B;&#x4F9D;&#x5B58;&#x3067;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x540C;&#x3058;&#x5206;&#x5B50;&#x6A5F;&#x80FD;&#x306F;&#x30D5;&#x30A3;&#x30D6;&#x30ED;&#x30CD;&#x30AF;&#x30C1;&#x30F3;&#x306E; COS7 &#x7D30;&#x80DE;&#x306E;&#x5E83;&#x304C;&#x308A;&#x3092;&#x9AD8;&#x3081;&#x308B;&#x305F;&#x3081;&#x306B; Dab2 &#x304C;&#x5FC5;&#x8981;&#x3067;&#x3059;&#x3002;&#x62E1;&#x6563;&#x30BB;&#x30EB;&#x3092;&#x5F37;&#x5316;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B; Dab2 &#x306E; p82 &#x30A2;&#x30A4;&#x30BD; &#x30D5;&#x30A9;&#x30FC;&#x30E0;&#x306E;&#x80FD;&#x529B;&#x306F;&#x3001;HeLa &#x7D30;&#x80DE;&#x3068; HBL &#x7D30;&#x80DE; &#xFF08;&#x3072;&#x3068;&#x4E73;&#x817A;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;) &#x306E;&#x4E21;&#x65B9;&#x3067;&#x78BA;&#x8A8D;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;COS7 GFP p82 &#x767A;&#x73FE;&#x7D30;&#x80DE;&#x3057;&#x3001;&#x30D5;&#x30A3;&#x30D6;&#x30ED;&#x30CD;&#x30AF;&#x30C1;&#x30F3;&#x96C6;&#x4E2D;&#x306B;&#x30ED;&#x30B0;&#x30AA;&#x30F3; beta1 &#x30A4;&#x30F3;&#x30C6;&#x30B0;&#x30EA;&#x30F3; &#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; p82 &#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x306B;&#x30E1;&#x30C3;&#x30AD;&#x3057;&#x307E;&#x3059;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x30BB;&#x30EB;&#x3092;&#x5C55;&#x958B;&#x3001;&#x4E2D;&#x306B; p82 &#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; &#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x96C6;&#x4E2D;&#x521D;&#x671F;&#x7D30;&#x80DE;-&#x30DE;&#x30C8;&#x30EA;&#x30C3;&#x30AF;&#x30B9;&#x306E;&#x9023;&#x7D61;&#x5148;&#x306E;&#x30B5;&#x30A4;&#x30C8;&#x3067;&#x3001;&#x6B20;&#x5E2D;&#x3057;&#x3066;&#x3044;&#x308B;&#x5F37;&#x70C8;&#x306A;&#x819C;&#x3092; ruffling &#x306E;&#x5730;&#x57DF;&#x304B;&#x3089;&#x3002;Dab2 &#x3068;&#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; &#x30A4;&#x30F3;&#x30C6;&#x30B0;&#x30EA;&#x30F3;&#x3092;&#x4ECB;&#x3057;&#x305F;&#x7D30;&#x80DE;&#x306E;&#x5E83;&#x304C;&#x308A;&#x306E;&#x305F;&#x3081;&#x306B;&#x5F79;&#x5272;&#x3092;&#x63D0;&#x6848;&#x3059;&#x308B;.

Dab2 &#x30AF;&#x30E9;&#x30B9;&#x30EA;&#x30F3; &#x30A2;&#x30BB;&#x30F3;&#x30D6;&#x30EA;&#x304A;&#x3088;&#x3073;&#x30BB;&#x30EB;&#x3092;&#x8ABF;&#x6574;&#x3057;&#x307E;&#x3059;&#x3002;

&#xBA64;&#xBE0C;&#xB808;&#xC778; &#xBC0F; &#xCF54;&#xD305;&#xB41C; &#xAD6C; &#xB369;&#xC774;&#xC5D0; &#xC5B4;&#xC148;&#xBE14;&#xB9AC;&#xC758; clathrin &#xBAA8;&#xC9D1; endocytic &#xC5B4;&#xB311;&#xD130;&#xC640; &#xD2B9;&#xC815; &#xC9C0;&#xC9C8; microenvironment&#xC758; &#xCEE8;&#xD14D;&#xC2A4;&#xD2B8;&#xC5D0;&#xC11C; &#xB2E4;&#xB978; &#xADDC;&#xC81C; &#xB2E8;&#xBC31;&#xC9C8;&#xC758; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC5D0;&#xC11C; &#xC720;&#xB798;&#xD55C; &#xB2E4;. Dab2 (&#xC7A5;&#xC560;&#xC778; 2) mitotic phosphoprotein &#xC774;&#xBA70; clathrin &#xC911;&#xC7AC; endocytosis monomeric &#xC5B4;&#xB311;&#xD130;. &#xD604;&#xC7AC;&#xC758; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C; &#xB2E4;&#xB978; isoforms&#xC758; GFP (&#xB179;&#xC0C9; &#xD615;&#xAD11; &#xB2E8;&#xBC31;&#xC9C8;) &#xD4E8;&#xC804; &#xAD6C;&#xC870;&#xC640; &#xB3CC;&#xC5F0;&#xBCC0;&#xC774; &#xC950; dab2&#xC758; &#xACE0;&#xC6A9; &#xD558; &#xACE0; &#xD06C;&#xAE30;, &#xC720;&#xD1B5; &#xBC0F; clathrin &#xC5B4;&#xC148;&#xBE14;&#xB9AC;&#xC758; &#xC5ED;&#xD559;&#xC5D0; &#xBBF8;&#xCE58;&#xB294; &#xC601;&#xD5A5;&#xC774; &#xD2B9;&#xC9D5;. &#xC720;&#xB3C4; &#xB41C; COS7 &#xC140;&#xC758; dab2&#xC758; p82 isoform&#xC758; &#xD45C;&#xD604; &#xD5A5;&#xC0C1; &#xB41C; &#xC218;&#xC900;&#xC758; &#xD50C;&#xB77C;&#xC988;&#xB9C8; &#xBA64;&#xBE0C;&#xB808;&#xC778;&#xC5D0;&#xC11C; clathrin &#xC5B4;&#xC148;&#xBE14;&#xB9AC; &#xD655;&#xB300;. AP2 &#xB4F1; &#xCD94;&#xAC00; endocytic &#xB2E8;&#xBC31;&#xC9C8; &#xC9D1;&#xC911; p82 clathrin &#xC5B4;&#xC148;&#xBE14;&#xB9AC; (&#xC5B4;&#xB311;&#xD130; &#xB2E8;&#xBC31;&#xC9C8; 2) &#xBC0F; epsin, &#xC801;&#xADF9;&#xC801;&#xC73C;&#xB85C; &#xB9C9;&#xACFC; cytosolic &#xC11C;&#xBE0C; &#xC0AC;&#xC774; p82 &#xBC0F; clathrin exchange&#xB294; &#xB3D9;&#xC801; &#xAD6C;&#xC870;. P82 &#xB2A5;&#xB825; &#xD655;&#xB300; clathrin &#xC5B4;&#xC148;&#xBE14;&#xB9AC; &#xC720;&#xB3C4; &#xAE30;&#xB2A5; PTB &#xB3C4;&#xBA54;&#xC778; (phosphotyrosine &#xBC14;&#xC778;&#xB529; &#xB3C4;&#xBA54;&#xC778;)&#xC5D0; &#xBC14;&#xC778;&#xB529; clathrin &#xBC0F; &#xC778;&#xC9C0;&#xC9C8;, &#xADF8;&#xB9AC;&#xACE0; PTB &#xB3C4;&#xBA54;&#xC778; &#xC55E;&#xC5D0; &#xC9C4;&#xD654; &#xC801;&#xC73C;&#xB85C; &#xBCF4;&#xC874; &#xD558; &#xACE0; &#xC0C8;&#xB85C; &#xC2DD;&#xBCC4; &#xB41C; &#xD3F4; &#xB9AC; &#xB9AC; &#xC2E0; &#xC2A4;&#xD2B8;&#xB808;&#xCE58;&#xC758; &#xC874;&#xC7AC; &#xC5EC;&#xBD80;&#xC5D0; &#xB530;&#xB77C; &#xB2EC;&#xB77C; &#xC9D1;&#xB2C8;&#xB2E4;. &#xC774; &#xAC19;&#xC740; &#xBD84;&#xC790; &#xAE30;&#xB2A5;&#xC740; Dab2 fibronectin COS7 &#xC140;&#xC758; &#xD655;&#xC0B0;&#xC744; &#xD5A5;&#xC0C1; &#xC2DC;&#xD0A4;&#xAE30; &#xC704;&#xD574; &#xD544;&#xC694; &#xD569;&#xB2C8;&#xB2E4;. Dab2&#xC758; p82 isoform &#xC788;&#xAC8C; &#xC140; &#xD655;&#xC0B0; &#xAC15;&#xD654; HeLa &#xC138;&#xD3EC;&#xC640; HBL &#xC138;&#xD3EC; (&#xC778;&#xAC04;&#xC758; &#xC720; &#xBC29; &#xC0C1;&#xD53C; &#xC138;&#xD3EC;)&#xC5D0;&#xC11C; &#xD655;&#xC778; &#xB410;&#xB2E4;. COS7 GFP p82 &#xD45C;&#xD604; &#xC138;&#xD3EC; &#xBC0F; clathrin p82 &#xC5B4;&#xC148;&#xBE14;&#xB9AC;&#xB85C; beta1 integrin fibronectin &#xC9D1;&#xC911;&#xC5D0; &#xB3C4;&#xAE08;. &#xB610;&#xD55C;, &#xC140;, &#xD655;&#xC0B0; &#xD558;&#xB294; &#xB3D9;&#xC548; p82 clathrin &#xC5B4;&#xC148;&#xBE14;&#xB9AC; &#xCD08;&#xAE30; &#xC138;&#xD3EC;-&#xB9E4;&#xD2B8;&#xB9AD;&#xC2A4; &#xC5F0;&#xB77D;&#xCC98; &#xC0AC;&#xC774;&#xD2B8;&#xC5D0;&#xC11C; &#xC9D1;&#xC911; &#xACE0; &#xACB0; &#xC11D; &#xD558;&#xB294; &#xAC15;&#xB82C;&#xD55C; &#xB9C9; &#xBB3C;&#xACB0;&#xC774;&#xC758; &#xC601;&#xC5ED;&#xC5D0;&#xC11C;. &#xC6B0;&#xB9AC;&#xB294; Dab2 &#xBC0F; clathrin integrin &#xC911;&#xC7AC; &#xC140; &#xD655;&#xC0B0;&#xC5D0; &#xC5ED;&#xD560;&#xC744; &#xC81C;&#xC548;&#xD569;&#xB2C8;&#xB2E4;.

Dab2 clathrin &#xC5B4;&#xC148;&#xBE14;&#xB9AC; &#xBC0F; &#xC140; &#xD655;&#xC0B0;&#xC744; &#xC870;&#xC808;.

La contrataci&oacute;n de clatrina a la membrana y su Asamblea en Tunica resulta de su interacci&oacute;n con adaptadores endoc&iacute;ticas y otras prote&iacute;nas reguladoras en el contexto de un microambiente de l&iacute;pidos espec&iacute;ficos. Dab2 (funci&oacute;n 2) es una fosfoprote&iacute;na mit&oacute;tica y un adaptador monom&eacute;rico de endocitosis mediada por clatrina. En el presente estudio, emplearon GFP (prote&iacute;na verde fluorescente) fusi&oacute;n construcciones de diferentes isoformas y mutantes de rata Dab2 y caracteriza su efecto sobre el tama&ntilde;o, distribuci&oacute;n y din&aacute;mica de asambleas de clatrina. Mejorado los niveles de expresi&oacute;n de la isoforma p82 de Dab2 en las c&eacute;lulas COS7 inducida agrandado clatrina asambleas en la membrana plasm&aacute;tica. Asambleas P82-clatrina, que concentran prote&iacute;nas endoc&iacute;ticas adicionales, como AP2 (prote&iacute;na adaptadora 2) y epsin, son estructuras din&aacute;micas que cambio p82 tanto clatrina activamente entre las subpoblaciones unida a la membrana y el citosol. La capacidad de inducir asambleas de clatrina ampliada de p82 depende de la presencia de un dominio funcional de PTB (dominio phosphotyrosine-obligatorio), en Uni&oacute;n a la clatrina y fosfol&iacute;pidos y en un tramo de poli-lisina reci&eacute;n identificados y evolutivamente conservadas que precede el dominio PTB. Estas mismas caracter&iacute;sticas moleculares son necesarias para Dab2 mejorar la difusi&oacute;n de las c&eacute;lulas COS7 de fibronectina. La capacidad de la isoforma p82 de Dab2 para mejorar la c&eacute;lula separarse fue confirmada en c&eacute;lulas HeLa y c&eacute;lulas HBL (c&eacute;lulas epiteliales de mama humana). COS7 c&eacute;lulas expresando GFP-p82 y plateado a la fibronectina concentrado la integrina beta1 en asambleas de clatrina-p82. Adem&aacute;s, durante la difusi&oacute;n de la c&eacute;lula, asambleas p82-clatrina se concentran en el sitio del contacto inicial c&eacute;lula-matriz y est&aacute;n ausentes de las regiones de la membrana intensa fruncido. Proponemos un papel para Dab2 y clatrina en la difusi&oacute;n de la integrina mediada por c&eacute;lulas.

Dab2 regula el ensamble de clatrina y separarse de la c&eacute;lula.

The aim of the present study was to examine the effects of music relaxation on insomnia and emotional measures in people living with schizophrenia. Twenty-four people living with schizophrenia participated in the study. The study involved a 7-day running-in no-treatment period, followed by a 7-day experimental period. Treatment consisted of music relaxation played at bedtime. During each of these periods, participants' sleep was continuously monitored with a wrist actigraph, and participants completed a wide spectrum of questionnaires. Results showed an improvement in sleep latency and sleep efficiency after the music relaxation was played. Likewise, music relaxation was shown to improve participants' total psychopathology score (PANSS) as well as their level of depression. Moreover, a significant correlation was found between reduction in level of situational anxiety and improvement in sleep efficiency. The findings suggest the beneficial effect of music relaxation as a treatment both for insomnia and for emotional measures in people living with schizophrenia.

The effects of music relaxation on sleep quality and emotional measures in people living with schizophrenia.

Une propri&eacute;t&eacute; essentielle de toutes les cellules est la capacit&eacute; &agrave; sortir de la division cellulaire active et de persister dans un &eacute;tat de repos. Pour les microorganismes unicellulaires, cela se produit principalement en r&eacute;ponse &agrave; la privation des &eacute;l&eacute;ments nutritifs. Nous avons &eacute;tudi&eacute; les conditions g&eacute;n&eacute;tiques pour la survie de Saccharomyces cerevisiae quand priv&eacute;es ou l&#39;autre des deux &eacute;l&eacute;ments nutritifs : phosphate ou leucine. Nous avons mesur&eacute; la survie de presque tous les mutants de levure haplo&iuml;de de null dans une population mixte &agrave; l&#39;aide d&#39;une m&eacute;thode de s&eacute;quen&ccedil;age quantitative qui permet d&#39;estimer l&#39;abondance de chaque mutant sur la base de la fr&eacute;quence des codes-barres mol&eacute;culaires uniques. Famine au phosphate se traduit par une demi-vie de population de 337 h alors que la famine pour la leucine se traduit par une demi-vie de 27,7 hr. Pour mesurer la survie des mutants individuels dans chaque population, nous avons d&eacute;velopp&eacute; un cadre statistique qui prend en compte les multiples sources de variation exp&eacute;rimentale. De l&#39;identit&eacute; des g&egrave;nes dont les mutations affectent fortement la survie, nous identifions des preuves g&eacute;n&eacute;tiques pour plusieurs processus cellulaires affectant la survie durant le je&ucirc;ne en &eacute;l&eacute;ments nutritifs, y compris d&#39;autophagie, remodelage, ARNm traitement et fonction du cytosquelette de la chromatine. En outre, nous avons trouv&eacute; des preuves que mitochondriale et peroxysomes fonction est n&eacute;cessaire pour la survie. Nos m&eacute;thodes exp&eacute;rimentales et analytiques repr&eacute;sentent une approche quantitative et efficace pour caract&eacute;riser les fonctions g&eacute;n&eacute;tiques et r&eacute;seaux avec une r&eacute;solution sans pr&eacute;c&eacute;dent et identifi&eacute; des interactions g&eacute;notype-par-environnement qui ont des implications importantes pour l&#39;interpr&eacute;tation des &eacute;tudes de vieillissement et de la quiescence chez la levure.

Au niveau du syst&egrave;me analyse des g&egrave;nes et fonctions affectant la survie durant le je&ucirc;ne en nutriments chez Saccharomyces cerevisiae.

An essential property of all cells is the ability to exit from active cell division and persist in a quiescent state. For single-celled microbes this primarily occurs in response to nutrient deprivation. We studied the genetic requirements for survival of Saccharomyces cerevisiae when starved for either of two nutrients: phosphate or leucine. We measured the survival of nearly all nonessential haploid null yeast mutants in mixed populations using a quantitative sequencing method that estimates the abundance of each mutant on the basis of frequency of unique molecular barcodes. Starvation for phosphate results in a population half-life of 337 hr whereas starvation for leucine results in a half-life of 27.7 hr. To measure survival of individual mutants in each population we developed a statistical framework that accounts for the multiple sources of experimental variation. From the identities of the genes in which mutations strongly affect survival, we identify genetic evidence for several cellular processes affecting survival during nutrient starvation, including autophagy, chromatin remodeling, mRNA processing, and cytoskeleton function. In addition, we found evidence that mitochondrial and peroxisome function is required for survival. Our experimental and analytical methods represent an efficient and quantitative approach to characterizing genetic functions and networks with unprecedented resolution and identified genotype-by-environment interactions that have important implications for interpretation of studies of aging and quiescence in yeast.

System-level analysis of genes and functions affecting survival during nutrient starvation in Saccharomyces cerevisiae.

Una propriet&agrave; essenziale di tutte le cellule &egrave; la capacit&agrave; di uscire dalla divisione cellulare attivo e persistere in uno stato quiescente. Per i singoli-celled microbi questo si verifica principalmente in risposta alla privazione dei nutrienti. Abbiamo studiato i requisiti genetici per la sopravvivenza di Saccharomyces cerevisiae quando fame per una delle due sostanze nutritive: fosfato o leucina. Abbiamo misurato la sopravvivenza di quasi tutti i non essenziali mutanti aploide lievito null in popolazioni miste, utilizzando un metodo di sequenziamento quantitativa che le stime di abbondanza di ogni mutante sulla base della frequenza di unico Molekulare codici a barre. Fame per fosfato risultati in un tempo di dimezzamento popolazione di 337 hr mentre fame per la leucina si traduce in un tempo di dimezzamento di 27,7 hr. Per misurare la sopravvivenza dei singoli mutanti in ogni popolazione abbiamo sviluppato un quadro statistico che rappresenta le molteplici fonti di variazione sperimentale. Dalle identit&agrave; dei geni in cui mutazioni fortemente influenzano la sopravvivenza, identifichiamo le prove genetiche per diversi processi cellulari che influenzano la sopravvivenza durante l&#39;inedia dei nutrienti, tra cui autophagy, chromatin che ritocca, mRNA di elaborazione e la funzione del citoscheletro. Inoltre, abbiamo trovato prove che mitocondriale e dei perossisomi funzione &egrave; necessaria per la sopravvivenza. I nostri metodi analitici e sperimentali rappresentano un approccio efficace e quantitativo per la caratterizzazione genetiche funzioni e reti con risoluzione senza precedenti e identificate interazioni genotipo-da-ambiente che hanno importanti implicazioni per l&#39;interpretazione degli studi di invecchiamento e di quiescenza in lievito.

Livello di sistema di analisi dei geni e delle funzioni che riguardano la sopravvivenza durante l&#39;inedia nutrienti in Saccharomyces cerevisiae.

Genetically identical cells grown in the same culture display striking cell-to-cell heterogeneity in gene expression and other traits. A crucial challenge is to understand how much of this heterogeneity reflects the noise tolerance of a robust system and how much serves a biological function. In bacteria, stochastic gene expression results in cell-to-cell heterogeneity that might serve as a bet-hedging mechanism, allowing a few cells to survive through an antimicrobial treatment while others perish. Despite its clinical importance, the molecular mechanisms underlying bet hedging remain unclear. Here, we investigate the mechanisms of bet hedging in Saccharomyces cerevisiae using a new high-throughput microscopy assay that monitors variable protein expression, morphology, growth rate, and survival outcomes of tens of thousands of yeast microcolonies simultaneously. We find that clonal populations display broad distributions of growth rates and that slow growth predicts resistance to heat killing in a probabalistic manner. We identify several gene products that are likely to play a role in bet hedging and confirm that Tsl1, a trehalose-synthesis regulator, is an important component of this resistance. Tsl1 abundance correlates with growth rate and replicative age and predicts survival. Our results suggest that yeast bet hedging results from multiple epigenetic growth states determined by a combination of stochastic and deterministic factors.

Bet hedging in yeast by heterogeneous, age-correlated expression of a stress protectant.

In microbial populations, growth initiation and proliferation rates are major components of fitness and therefore likely targets of selection. We used a high-throughput microscopy assay, which enables simultaneous analysis of tens of thousands of microcolonies, to determine the sources and extent of growth rate variation in the budding yeast (Saccharomyces cerevisiae) in different glucose environments. We find that cell growth rates are regulated by the extracellular concentration of glucose as proposed by Monod (1949), but that significant heterogeneity in growth rates is observed among genetically identical individuals within an environment. Yeast strains isolated from different geographic locations and habitats differ in their growth rate responses to different glucose concentrations. Inheritance patterns suggest that the genetic determinants of growth rates in different glucose concentrations are distinct. In addition, we identified genotypes that differ in the extent of variation in growth rate within an environment despite nearly identical mean growth rates, providing evidence that alleles controlling phenotypic variability segregate in yeast populations. We find that the time to reinitiation of growth (lag) is negatively correlated with growth rate, yet this relationship is strain-dependent. Between environments, the respirative activity of individual cells negatively correlates with glucose abundance and growth rate, but within an environment respirative activity and growth rate show a positive correlation, which we propose reflects differences in protein expression capacity. Our study quantifies the sources of genetic and nongenetic variation in cell growth rates in different glucose environments with unprecedented precision, facilitating their molecular genetic dissection.

Genetic and Nongenetic Determinants of Cell Growth Variation Assessed by High-Throughput Microscopy.

The mode and timing of virally-induced cell death withhold the potential of regulating viral yield, viral transmission and the severity of virally-induced disease. Orbiviruses such as the epizootic hemorrhagic disease virus (EHDV) are nonenveloped and cytolytic. To date, the death of cells infected with EHDV, the signal transduction pathways involved in this process and the consequence of their inhibition have yet to be characterized. Here, we report that the Ibaraki strain of EHDV2 (EHDV2-IBA) induces apoptosis, autophagy, a decrease in cellular protein synthesis, the activation of c-Jun N-terminal kinase (JNK) and the phosphorylation of the JNK substrate c-Jun. The production of infectious virions was decreased upon inhibition of apoptosis with the pan-caspase inhibitor Q-VD-OPH; upon inhibition of autophagy with 3-methyladenine or via the knockout of the autophagy regulator Atg5; or upon treatment of infected cells with the JNK inhibitor SP600125 or the cyclin-dependent-kinase (cdk) inhibitor roscovitine, which also inhibited c-Jun phosphorylation. Moreover, Q-VD-OPH, SP600125 and roscovitine partially reduced EHDV2-IBA-induced cell death, and roscovitine diminished the induction of autophagy by EHDV2-IBA. Taken together, our results imply that EHDV induces and benefits from the activation of signaling pathways involved in cell stress and death.

Naomi Ziv

Center for Genomics and Systems Biology,
Department of Biology,
Center for Genomics and Systems Biology, Department of Biology

New York University

The Use of Chemostats in Microbial Systems Biology

Naomi Ziv

Center for Genomics and Systems Biology,Department of Biology,Center for Genomics and Systems Biology, Department of Biology

New York University

The Use of Chemostats in Microbial Systems Biology

Center for Genomics and Systems Biology,
Department of Biology,
Center for Genomics and Systems Biology, Department of Biology