retrograde-perfusion-filling-mouse-coronary-vasculature-as

Retrograde Perfusion and Filling of Mouse Coronary Vasculature as Preparation for Micro Computed Tomography Imaging

Visualization of the vasculature is becoming increasingly important for understanding many different disease states. While several techniques exist for ...

advanced-techniques-for-studying-blood-flow

Advanced Techniques for Studying Blood Flow

ARTICLES DISCUSSED:
Tang, G. L., Kim, K. J. Laser Doppler perfusion imaging in the mouse hindlimb. Journal of Visualized Experiments. (170), e62012 ...

University of Washington

Sunnybrook Research Institute

University of Toronto

&#x4EA8;&#x5EF7;&#x987F;&#x6C0F;&#x821E;&#x8E48;&#x75C5;&#x548C;&#x516B;&#x4E2A;&#x76F8;&#x5173;&#x795E;&#x7ECF;&#x9000;&#x884C;&#x6027;&#x75BE;&#x75C5;&#xFF0C;&#x7A81;&#x53D8;&#x57FA;&#x56E0;&#x7684;&#x7814;&#x7A76;&#x5DF2;&#x786E;&#x5B9A; polyglutamine (polyQ) &#x6269;&#x4EA7;&#x4E3A;&#x7EC6;&#x80DE;&#x6BD2;&#x6027;&#x7684;&#x57FA;&#x7840;&#x3002;&#x8FD9;&#x4E00;&#x53D1;&#x73B0;&#x5DF2;&#x5BFC;&#x81F4;&#x75BE;&#x75C5;&#x5047;&#x8BBE;&#x8BE5;&#x86CB;&#x767D;&#x8D28;&#x805A;&#x96C6;&#x548C;&#x7EC6;&#x80DE;&#x529F;&#x80FD;&#x969C;&#x788D;&#x53EF;&#x4EE5;&#x53D1;&#x751F;&#x5728;&#x5927;&#x7EA6; 40 &#x8C37;&#x6C28;&#x9170;&#x80FA;&#x6B8B;&#x7559;&#x7684;&#x9608;&#x503C;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x6D4B;&#x8BD5;&#x8FD9;&#x4E00;&#x5047;&#x8BBE;&#x7684;&#x9057;&#x4F20;&#x7269;&#x8D28;&#x6807;&#x8BB0;&#x7684; polyQ &#x86CB;&#x767D; (Q29&#x3001; Q33&#x3001; Q35&#x3001; Q40&#x3001; &#x548C; Q44) &#x6746;&#x7EBF;&#x866B;&#x548C;&#x5E74;&#x8F7B;&#x6210;&#x5E74;&#x4EBA;&#x5C55;&#x793A;&#x5728; 35-40 glutamines &#x5173;&#x8054;&#x86CB;&#x767D;&#x805A;&#x96C6;&#x7684;&#x5916;&#x89C2;&#x548C;&#x52A8;&#x529B;&#x7684;&#x635F;&#x5931;&#x660E;&#x663E;&#x8FB9;&#x754C;&#x7684;&#x653E;&#x6620;&#x4F53;&#x58C1;&#x808C;&#x8089;&#x7EC6;&#x80DE;&#x4E2D;&#x7684;&#x8868;&#x8FBE;&#x3002;&#x5947;&#x602A;&#x7684;&#x662F;&#xFF0C;&#x8868;&#x793A;&#x9608;&#x503C;&#x9644;&#x8FD1; polyQ &#x91CD;&#x590D;&#x57FA;&#x56E0;&#x76F8;&#x540C;&#x7684;&#x52A8;&#x7269;&#x8868;&#x73B0;&#x51FA;&#x9AD8;&#x5EA6;&#x7684;&#x5916;&#x89C2;&#x86CB;&#x767D;&#x805A;&#x96C6;&#x548C;&#x7EC6;&#x80DE;&#x6BD2;&#x6027;&#xFF0C;&#x53D6;&#x51B3;&#x4E8E;&#x91CD;&#x590D;&#x957F;&#x5EA6;&#x548C;&#x52A0;&#x5267;&#x9648;&#x5316;&#x8FC7;&#x7A0B;&#x4E2D;&#x7684;&#x53D8;&#x5316;&#x3002;&#x57FA;&#x56E0;&#x51B3;&#x5B9A;&#x7684;&#x8870;&#x8001;&#x901A;&#x8DEF;&#x4E0E;&#x5E74;&#x9F84;&#x76F8;&#x5173;&#x4ECB;&#x5BFC; polyQ &#x805A;&#x5408;&#x548C;&#x7EC6;&#x80DE;&#x6BD2;&#x6027;&#x7684;&#x7EA7;&#x6570;&#x4E2D;&#x7684;&#x4F5C;&#x7528;&#x8868;&#x73B0;&#x51FA;&#x5EF6;&#x957F;&#x7684;&#x5BFF;&#x547D;&#x7684;&#x5E74;&#x9F84;-1 &#x7A81;&#x53D8;&#x4F53;&#x52A8;&#x7269;&#x7684;&#x80CC;&#x666F;&#x4E2D;&#x8868;&#x793A; Q82 &#x8FDB;&#x884C;&#x4E86;&#x6D4B;&#x8BD5;&#x3002;&#x6211;&#x4EEC;&#x6CE8;&#x610F;&#x5230; polyQ &#x6BD2;&#x6027;&#x663E;&#x8457;&#x5EF6;&#x8FDF;&#x548C;&#x86CB;&#x767D;&#x805A;&#x96C6;&#x7684;&#x5916;&#x89C2;&#x3002;&#x8FD9;&#x4E9B;&#x6570;&#x636E;&#x4E3A; polyQ &#x4ECB;&#x5BFC;&#x7684;&#x6BD2;&#x6027;&#x5B9E;&#x9A8C;&#x6D3B;&#x7684;&#x6709;&#x673A;&#x4F53;&#x4E2D;&#x7684;&#x9608;&#x503C;&#x5047;&#x8BF4;&#x63D0;&#x4F9B;&#x5B9E;&#x9A8C;&#x652F;&#x6301;&#xFF0C;&#x548C;&#x9608;&#x503C;&#x7684;&#x5F3A;&#x8C03;&#xFF0C;&#x4F5C;&#x4E3A;&#x4E00;&#x4E2A;&#x70B9;&#x7684;&#x9057;&#x4F20;&#x4FEE;&#x9970;&#x7B26;&#x548C;&#x8001;&#x5316;&#x5F71;&#x54CD;&#x751F;&#x5316;&#x73AF;&#x5883;&#x548C;&#x86CB;&#x767D;&#x7A33;&#x6001;&#x7684;&#x5355;&#x5143;&#x683C;&#x3002;

Polyglutamine &#x6269;&#x5C55;&#x86CB;&#x767D;&#x805A;&#x5408;&#x548C;&#x7EC6;&#x80DE;&#x6BD2;&#x6027;&#x7684;&#x9608;&#x503C;&#x662F;&#x52A8;&#x6001;&#x548C;&#x79C0;&#x4E3D;&#x9690;&#x6746;&#x7EBF;&#x866B;&#x4E2D;&#x8001;&#x5316;&#x7684;&#x5F71;&#x54CD;&#x3002;

Studies of the mutant gene in Huntington's disease, and for eight related neurodegenerative disorders, have identified polyglutamine (polyQ) expansions as a basis for cellular toxicity. This finding has led to a disease hypothesis that protein aggregation and cellular dysfunction can occur at a threshold of approximately 40 glutamine residues. Here, we test this hypothesis by expression of fluorescently tagged polyQ proteins (Q29, Q33, Q35, Q40, and Q44) in the body wall muscle cells of Caenorhabditis elegans and show that young adults exhibit a sharp boundary at 35-40 glutamines associated with the appearance of protein aggregates and loss of motility. Surprisingly, genetically identical animals expressing near-threshold polyQ repeats exhibited a high degree of variation in the appearance of protein aggregates and cellular toxicity that was dependent on repeat length and exacerbated during aging. The role of genetically determined aging pathways in the progression of age-dependent polyQ-mediated aggregation and cellular toxicity was tested by expressing Q82 in the background of age-1 mutant animals that exhibit an extended lifespan. We observed a dramatic delay of polyQ toxicity and appearance of protein aggregates. These data provide experimental support for the threshold hypothesis of polyQ-mediated toxicity in an experimental organism and emphasize the importance of the threshold as a point at which genetic modifiers and aging influence biochemical environment and protein homeostasis in the cell.

The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans.

&Eacute;tudes du g&egrave;ne mutant dans la maladie de Huntington et pour huit maladies neurod&eacute;g&eacute;n&eacute;ratives connexes, ont identifi&eacute; des extensions polyglutamine (polyQ) comme base de la toxicit&eacute; cellulaire. Cette constatation a men&eacute; &agrave; une hypoth&egrave;se de maladie cette agr&eacute;gation de la prot&eacute;ine et dysfonctionnement cellulaire peut survenir &agrave; un seuil d&#39;environ 40 r&eacute;sidus glutamine. Ici, nous avons test&eacute; cette hypoth&egrave;se par l&#39;expression des prot&eacute;ines de polyQ fluorescent &eacute;tiquet&eacute; (Q29, Q33, Q35, Q40 et Q44) dans les cellules musculaires de paroi corporelle de Caenorhabditis elegans et montrent que les jeunes adultes pr&eacute;sentent une borne pointue &agrave; 35-40 glutamines associ&eacute;e &agrave; l&#39;apparition d&#39;agr&eacute;gats de prot&eacute;ines et la perte de la mobilit&eacute;. &Eacute;tonnamment, animaux g&eacute;n&eacute;tiquement identiques se d&eacute;clarant pr&egrave;s de seuil polyQ r&eacute;p&eacute;titions pr&eacute;sentaient un degr&eacute; &eacute;lev&eacute; de variation dans l&#39;apparence d&#39;agr&eacute;gats de prot&eacute;ines et de la toxicit&eacute; cellulaire qui d&eacute;pendait de la longueur de la r&eacute;p&eacute;tition et exacerb&eacute; au cours du vieillissement. Le r&ocirc;le des voies de vieillissement g&eacute;n&eacute;tiquement d&eacute;termin&eacute;s dans la progression de l&#39;agr&eacute;gation induite par polyQ selon l&#39;&acirc;ge et la toxicit&eacute; cellulaire a &eacute;t&eacute; test&eacute; en exprimant Q82 en arri&egrave;re-plan d&#39;&acirc;ge-1 animaux mutants qui pr&eacute;sentent une dur&eacute;e de vie prolong&eacute;e. Nous avons observ&eacute; un retard dramatique de polyQ toxicit&eacute; et l&#39;apparence d&#39;agr&eacute;gats de prot&eacute;ines. Ces donn&eacute;es offrent support exp&eacute;rimental pour l&#39;hypoth&egrave;se du seuil de toxicit&eacute; induite par les polyQ dans un organisme exp&eacute;rimental et mettent l&#39;accent sur l&#39;importance du seuil comme un point au cours de laquelle vieillissement et modificateurs g&eacute;n&eacute;tiques influencent l&#39;environnement biochimique et l&#39;hom&eacute;ostasie des prot&eacute;ines dans la cellule.

Le seuil pour l&#39;expansion de polyglutamine prot&eacute;ine cellulaire et agr&eacute;gation de toxicit&eacute; est dynamique et influenc&eacute;e par le vieillissement chez Caenorhabditis elegans.

Die Schwelle f&#xFC;r Polyglutamin-Erweiterung Proteinaggregation und zellul&#xE4;re Toxizit&#xE4;t ist dynamisch und gepr&#xE4;gt durch Alterung in Caenorhabditis elegans.

Studi del gene mutante nella malattia di Huntington e per otto patologie neurodegenerative correlate, hanno identificato le espansioni delle poliglutamine (polyQ) come base per la tossicit&agrave; cellulare. Questa constatazione ha portato ad un&#39;ipotesi di malattia che aggregazione proteica e disfunzione cellulare pu&ograve; verificarsi in una soglia di circa 40 residui di glutammina. Qui, ci prova questa ipotesi di espressione delle proteine polyQ fluorescente contrassegnati (D29, Q33, Q35, Q40 e Q44) nelle cellule muscolari della parete di corpo di Caenorhabditis elegans e mostrano che i giovani adulti presentano un forte limite al 35-40 glutamines associati con la comparsa di aggregati di proteine e la perdita di motilit&agrave;. Sorprendentemente, animali geneticamente identici esprimendo polyQ vicino a soglia ripete esposto un alto grado di variazione nell&#39;aspetto degli aggregati di proteina e tossicit&agrave; cellulare che dipendeva dalla lunghezza di ripetizione e aggravata durante l&#39;invecchiamento. Il ruolo delle vie di invecchiamento geneticamente determinata nella progressione di et&agrave;-dipendente polyQ-mediata aggregazione e tossicit&agrave; cellulare &egrave; stato testato da esprimere Q82 sullo sfondo di et&agrave;-1 animali mutanti che presentano una durata estesa. Abbiamo osservato un drammatico ritardo polyQ tossicit&agrave; e l&#39;aspetto degli aggregati della proteina. Questi dati forniscono il supporto sperimentale per l&#39;ipotesi della soglia di tossicit&agrave; polyQ-mediata in un organismo sperimentale e sottolineano l&#39;importanza della soglia come un punto in cui invecchiamento e modificatori genetici influenzano ambiente biochimico e omeostasi proteine nella cellula.

La soglia per l&#39;espansione delle poliglutamine proteina aggregazione e cellulare tossicit&agrave; &egrave; influenzata dall&#39;invecchiamento in Caenorhabditis elegans e dinamica.

&#x30CF;&#x30F3;&#x30C1;&#x30F3;&#x30C8;&#x30F3;&#x75C5;&#x3001;&#x304A;&#x3088;&#x3073; 8 &#x3064;&#x306E;&#x95A2;&#x9023;&#x795E;&#x7D4C;&#x5909;&#x6027;&#x75BE;&#x60A3;&#x306E;&#x305F;&#x3081;&#x306E;&#x7A81;&#x7136;&#x5909;&#x7570;&#x907A;&#x4F1D;&#x5B50;&#x306E;&#x7814;&#x7A76; (&#x30DD;&#x30EA; q) &#x306E;&#x4F38;&#x9577;&#x30DD;&#x30EA;&#x30B0;&#x30EB;&#x30BF;&#x30DF;&#x30F3;&#x7D30;&#x80DE;&#x6BD2;&#x6027;&#x306E;&#x305F;&#x3081;&#x306E;&#x57FA;&#x790E;&#x3068;&#x3057;&#x3066;&#x8B58;&#x5225;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x306E;&#x767A;&#x898B;&#x75BE;&#x60A3;&#x4EEE;&#x8AAC;&#x306B;&#x305D;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x51DD;&#x96C6;&#x3064;&#x306A;&#x304C;&#x3063;&#x3066;&#x3044;&#x308B;&#x3057;&#x3001;&#x7D30;&#x80DE;&#x6A5F;&#x80FD;&#x969C;&#x5BB3;&#x306E;&#x7D04; 40 &#x306E;&#x30B0;&#x30EB;&#x30BF;&#x30DF;&#x30F3;&#x6B8B;&#x57FA;&#x306E;&#x3057;&#x304D;&#x3044;&#x5024;&#x306B;&#x767A;&#x751F;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x7DDA;&#x866B;&#x3068;&#x92ED;&#x3044;&#x5883;&#x754C;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x51DD;&#x96C6;&#x4F53;&#x306E;&#x5916;&#x89B3;&#x3068;&#x904B;&#x52D5;&#x6027;&#x306E;&#x640D;&#x5931;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x3066; 35 40 glutamines &#x3067;&#x306E;&#x5C55;&#x793A;&#x306B;&#x82E5;&#x3044;&#x5927;&#x4EBA;&#x30B7;&#x30E7;&#x30FC;&#x306E;&#x4F53;&#x58C1;&#x7B4B;&#x7D30;&#x80DE;&#x306B;&#x304A;&#x3051;&#x308B;&#x86CD;&#x5149;&#x30BF;&#x30B0; &#x30DD;&#x30EA; q &#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA; (Q29, Q33, Q35, Q40 &#x3068; Q44) &#x306E;&#x767A;&#x73FE;&#x306B;&#x3088;&#x3063;&#x3066;&#x3053;&#x306E;&#x4EEE;&#x8AAC;&#x3092;&#x30C6;&#x30B9;&#x30C8;&#x3057;&#x307E;&#x3059;&#x3002;&#x9A5A;&#x3044;&#x305F;&#x3053;&#x3068;&#x306B;&#x3001;&#x3057;&#x304D;&#x3044;&#x5024;&#x306B;&#x8FD1;&#x3044;&#x30DD;&#x30EA; q &#x7E70;&#x308A;&#x8FD4;&#x3057;&#x8868;&#x73FE;&#x3059;&#x308B;&#x907A;&#x4F1D;&#x7684;&#x306B;&#x540C;&#x4E00;&#x306E;&#x52D5;&#x7269;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x51DD;&#x96C6;&#x4F53;&#x3068;&#x30EA;&#x30D4;&#x30FC;&#x30C8;&#x306E;&#x9577;&#x3055;&#x306B;&#x4F9D;&#x5B58;&#x3057;&#x3066;&#x3044;&#x305F;&#x3057;&#x3001;&#x60AA;&#x5316;&#x306E;&#x8001;&#x5316;&#x6642;&#x306B;&#x7D30;&#x80DE;&#x6BD2;&#x6027;&#x306E;&#x5916;&#x89B3;&#x306E;&#x5909;&#x7570;&#x306E;&#x9AD8;&#x3044;&#x5C55;&#x793A;&#x3002;&#x5E74;&#x9F62;&#x4F9D;&#x5B58;&#x578B;&#x30DD;&#x30EA; q &#x3092;&#x4ECB;&#x3057;&#x305F;&#x96C6;&#x7D04;&#x3068;&#x7D30;&#x80DE;&#x6BD2;&#x6027;&#x306E;&#x9032;&#x884C;&#x306B;&#x907A;&#x4F1D;&#x7684;&#x306B;&#x6C7A;&#x5B9A;&#x8001;&#x5316;&#x7D4C;&#x8DEF;&#x306E;&#x5F79;&#x5272; Q82 &#x62E1;&#x5F35;&#x5BFF;&#x547D;&#x5C55;&#x793A;&#x5E74;&#x9F62; 1 &#x5909;&#x7570;&#x52D5;&#x7269;&#x306E;&#x30D0;&#x30C3;&#x30AF; &#x30B0;&#x30E9;&#x30A6;&#x30F3;&#x30C9;&#x3067;&#x8868;&#x73FE;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x30C6;&#x30B9;&#x30C8;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x30DD;&#x30EA; q &#x6BD2;&#x6027;&#x306E;&#x5287;&#x7684;&#x306A;&#x9045;&#x5EF6;&#x3068;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x51DD;&#x96C6;&#x4F53;&#x306E;&#x5916;&#x89B3;&#x3092;&#x89B3;&#x5BDF;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C7;&#x30FC;&#x30BF; &#x30DD;&#x30EA; q &#x3092;&#x4ECB;&#x3057;&#x305F;&#x6BD2;&#x6027;&#x5B9F;&#x9A13;&#x7684;&#x6709;&#x6A5F;&#x4F53;&#x306B;&#x304A;&#x3051;&#x308B;&#x3057;&#x304D;&#x3044;&#x5024;&#x4EEE;&#x8AAC;&#x3092;&#x5B9F;&#x9A13;&#x7684;&#x306A;&#x30B5;&#x30DD;&#x30FC;&#x30C8;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x3001;&#x3057;&#x304D;&#x3044;&#x5024;&#x3067;&#x907A;&#x4F1D;&#x4FEE;&#x98FE;&#x5B50;&#x3068;&#x8001;&#x5316;&#x306E;&#x751F;&#x5316;&#x5B66;&#x7684;&#x74B0;&#x5883;&#x3068;&#x7D30;&#x80DE;&#x5185;&#x306E;&#x86CB;&#x767D;&#x8CEA;&#x306E;&#x6052;&#x5E38;&#x6027;&#x5F71;&#x97FF;&#x70B9;&#x3068;&#x3057;&#x3066;&#x91CD;&#x8981;&#x6027;&#x3092;&#x5F37;&#x8ABF;&#x3057;&#x307E;&#x3059;&#x3002;

&#x30DD;&#x30EA;&#x30B0;&#x30EB;&#x30BF;&#x30DF;&#x30F3;&#x62E1;&#x5F35;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x51DD;&#x96C6;&#x3068;&#x7D30;&#x80DE;&#x6BD2;&#x6027;&#x306E;&#x3057;&#x304D;&#x3044;&#x5024;&#x306F;&#x3001;&#x52D5;&#x7684;&#x304A;&#x3088;&#x3073;&#x7DDA;&#x866B;&#x306E;&#x8001;&#x5316;&#x306B;&#x3088;&#x3063;&#x3066;&#x5F71;&#x97FF;&#x3092;&#x53CA;&#x307C;&#x3055;&#x3067;&#x3059;&#x3002;

&#xD5CC;&#xD305;&#xD134; &#xBCD1;, &#xADF8;&#xB9AC;&#xACE0; 8 &#xAC1C;&#xC758; &#xAD00;&#xB828;&#xB41C; &#xC2E0;&#xACBD; &#xD1F4;&#xD589; &#xC131; &#xC9C8;&#xD658;&#xC5D0; &#xB300; &#xD55C; &#xB3CC;&#xC5F0;&#xBCC0;&#xC774; &#xC720;&#xC804;&#xC790;&#xC758; &#xC5F0;&#xAD6C;&#xB294; &#xC138;&#xD3EC; &#xB3C5;&#xC131;&#xC5D0; &#xB300; &#xD55C; &#xADFC;&#xAC70;&#xB85C; polyglutamine (polyQ) &#xD655;&#xC7A5;&#xC744; &#xD655;&#xC778; &#xD588;&#xB2E4;. &#xC774; &#xCC3E;&#xB294; &#xADF8; &#xB2E8;&#xBC31;&#xC9C8; &#xC9D1;&#xACC4; &#xC9C8;&#xBCD1; &#xAC00;&#xC124;&#xC744; &#xC8FC;&#xB3C4;&#xD558; &#xACE0; &#xC138;&#xD3EC; &#xAE30;&#xB2A5; &#xC7A5;&#xC560; &#xC57D; 40 &#xAE00;&#xB8E8;&#xD0C0;&#xBBFC; &#xC794;&#xB958;&#xBB3C;&#xC758; &#xC784;&#xACC4;&#xAC12;&#xC5D0; &#xB3C4;&#xB2EC; &#xD588;&#xC2B5;&#xB2C8;&#xB2E4; &#xBC1C;&#xC0DD;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC5EC;&#xAE30;, &#xC6B0;&#xB9AC;&#xB294; Caenorhabditis elegans&#xC640; &#xC80A;&#xC740; &#xC131;&#xC778;&#xC5D0;&#xC11C; 35-40 glutamines &#xB2E8;&#xBC31;&#xC9C8;&#xC758; &#xBAA8;&#xC591; &#xBC0F; &#xC6B4;&#xB3D9; &#xC131; &#xC0C1;&#xC2E4;&#xACFC; &#xAD00;&#xB828; &#xB41C; &#xB0A0;&#xCE74;&#xB85C;&#xC6B4; &#xACBD;&#xACC4;&#xB97C; &#xC804;&#xC2DC; &#xD558;&#xB294; &#xC1FC;&#xC758; &#xBAB8; &#xBCBD; &#xADFC;&#xC721; &#xC138;&#xD3EC;&#xC5D0; &#xB193;&#xC5EC;&#xC788;&#xB294;&#xC9C0; &#xD0DC;&#xADF8; polyQ &#xB2E8;&#xBC31;&#xC9C8; (Q29, Q33, Q35, Q40, &#xBC0F; Q44)&#xC758; &#xD45C;&#xD604;&#xC73C;&#xB85C;&#xC774; &#xAC00;&#xC124;&#xC744; &#xD14C;&#xC2A4;&#xD2B8; &#xD569;&#xB2C8;&#xB2E4;. &#xB180;&#xB78D;&#xAC8C;&#xB3C4;, &#xC784;&#xACC4;&#xAC12; &#xADFC;&#xCC98; polyQ &#xBC18;&#xBCF5; &#xD45C;&#xD604; &#xD558;&#xB294; &#xC720;&#xC804;&#xC73C;&#xB85C; &#xB3D9;&#xC77C;&#xD55C; &#xB3D9;&#xBB3C; &#xB2E8;&#xBC31;&#xC9C8; &#xC9D1;&#xACC4; &#xBC0F; &#xBC18;&#xBCF5; &#xAE38;&#xC774;&#xC5D0; &#xC885;&#xC18D; &#xB418;&#xC5C8;&#xACE0; &#xB178;&#xD654; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xB354;&#xC6B1; &#xC545;&#xD654; &#xC138;&#xD3EC; &#xB3C5;&#xC131;&#xC758; &#xBAA8;&#xC591;&#xC5D0; &#xC788;&#xB294; &#xBCC0;&#xC774;&#xC758; &#xACE0;&#xCC28; &#xC804;&#xC2DC;. &#xC5F0;&#xB839;&#xC5D0; &#xB530;&#xB77C; polyQ &#xC911;&#xC7AC; &#xC9D1;&#xACC4; &#xBC0F; &#xC138;&#xD3EC; &#xB3C5;&#xC131;&#xC758; &#xC9C4;&#xD589;&#xC5D0; &#xC720;&#xC804;&#xC790; &#xACB0;&#xC815;&#xB41C; &#xB178;&#xD654; &#xD1B5;&#xB85C;&#xC758; &#xC5ED;&#xD560; &#xD655;&#xC7A5; &#xB41C; &#xC218;&#xBA85; &#xC804;&#xC2DC; &#xB098;&#xC774; 1 &#xB3CC;&#xC5F0;&#xBCC0;&#xC774; &#xB3D9;&#xBB3C; &#xBC30;&#xACBD;&#xC758; Q82 &#xD45C;&#xD604; &#xD558; &#xC5EC; &#xD14C;&#xC2A4;&#xD2B8;&#xB97C; &#xD588;&#xB2E4;. PolyQ &#xB3C5;&#xC131;&#xC758; &#xADF9;&#xC801;&#xC778; &#xC5F0;&#xAE30;&#xC640; &#xB2E8;&#xBC31;&#xC9C8;&#xC758; &#xBAA8;&#xC591;&#xC744; &#xAD00;&#xCC30;&#xD569;&#xB2C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xB370;&#xC774;&#xD130;&#xB294; &#xC2E4;&#xD5D8; &#xCCB4;&#xC5D0; &#xB3C5;&#xC131; polyQ &#xC911;&#xC7AC;&#xC758; &#xC784;&#xACC4;&#xAC12; &#xAC00;&#xC124;&#xC5D0; &#xB300; &#xD55C; &#xC2E4;&#xD5D8; &#xC9C0;&#xC6D0;&#xC744; &#xC81C;&#xACF5; &#xD558; &#xACE0;&#xB294; &#xC720;&#xC804; &#xD55C;&#xC815;&#xC790; &#xBC0F; &#xB178;&#xD654; &#xC601;&#xD5A5; &#xC0DD; &#xD654; &#xD655; &#xC801;&#xC778; &#xD658;&#xACBD;&#xACFC; &#xC140;&#xC5D0; &#xB2E8;&#xBC31;&#xC9C8; &#xD56D;&#xC0C1;&#xC131; &#xC810;&#xC73C;&#xB85C; &#xC784;&#xACC4;&#xAC12;&#xC758; &#xC911;&#xC694;&#xC131;&#xC744; &#xAC15;&#xC870;.

Polyglutamine &#xD655;&#xC7A5; &#xB2E8;&#xBC31;&#xC9C8; &#xC9D1;&#xACC4; &#xBC0F; &#xC138;&#xD3EC; &#xB3C5;&#xC131;&#xC5D0; &#xB300; &#xD55C; &#xC784;&#xACC4;&#xAC12;&#xC740; &#xC5ED;&#xB3D9;&#xC801;&#xC774; &#xACE0; Caenorhabditis elegans&#xC5D0; &#xB178;&#xD654;&#xC758; &#xC601;&#xD5A5;&#xC744;.

Estudios del gen mutante en la enfermedad de Huntington y para los trastornos neurodegenerativos relacionados con ocho, han identificado expansiones de poliglutaminas (poliQ) como base para la toxicidad celular. Este hallazgo ha llevado a la hip&oacute;tesis de una enfermedad agregaci&oacute;n de la prote&iacute;na y la disfunci&oacute;n celular puede ocurrir en un umbral de aproximadamente 40 residuos de glutamina. Aqu&iacute; ponemos a prueba esta hip&oacute;tesis por la expresi&oacute;n de prote&iacute;nas poliQ fluorescencia de etiquetado (Q29, Q33, Q35 Q40 y Q44) en las c&eacute;lulas musculares de la pared cuerpo de Caenorhabditis elegans y mostrar que los j&oacute;venes exhiben un fuerte l&iacute;mite en 35-40 glutaminas asociado con la aparici&oacute;n de agregados de prote&iacute;nas y p&eacute;rdida de la motilidad. Sorprendentemente, animales gen&eacute;ticamente id&eacute;nticos expresando cerca de umbral poliQ repeticiones exhiben un alto grado de variaci&oacute;n en la aparici&oacute;n de agregados proteicos y toxicidad celular que depend&iacute;a de la longitud de la repetici&oacute;n y exacerbado durante el envejecimiento. El papel de las v&iacute;as de envejecimiento gen&eacute;ticamente determinada en la progresi&oacute;n de agregaci&oacute;n de poliQ-mediada dependiente de la edad y la toxicidad celular fue probado expresando Q82 en el fondo de animales mutantes de edad que presentan una vida &uacute;til extendida. Observamos un dram&aacute;tico retraso de toxicidad poliQ y aparici&oacute;n de agregados proteicos. Estos datos proporcionan soporte experimental para la hip&oacute;tesis del umbral de toxicidad mediada por poliQ en un organismo experimental y enfatizan la importancia del umbral como un punto en que envejecimiento y modificadores gen&eacute;ticos influyen entorno bioqu&iacute;mico y homeostasis de prote&iacute;na en la c&eacute;lula.

El umbral de toxicidad de agregaci&oacute;n y celular de prote&iacute;nas poliglutaminas-expansi&oacute;n es din&aacute;mica e influenciado por envejecimiento en Caenorhabditis elegans.

&#x5668;&#x5B98;&#x53D1;&#x751F;&#x662F;&#x4E00;&#x4E2A;&#x590D;&#x6742;&#x7684;&#x8FC7;&#x7A0B;&#xFF0C;&#x9700;&#x8981;&#x591A;&#x4E2A;&#x5355;&#x5143;&#x683C;&#x7C7B;&#x578B;&#x4E0E;&#x53E6;&#x4E00;&#x4E2A;&#x76F8;&#x5173;&#x8054;&#xFF0C;&#x901A;&#x8FC7;&#x6B63;&#x786E;&#x7684;&#x5355;&#x5143;&#x683C;&#x7684;&#x63A5;&#x89E6;&#x548C;&#x5728;&#x6B63;&#x786E;&#x7684;&#x4F4D;&#x7F6E;&#xFF0C;&#x4EE5;&#x8FBE;&#x5230;&#x9002;&#x5F53;&#x7684;&#x5668;&#x5B98;&#x5F62;&#x6001;&#x4E0E;&#x529F;&#x80FD;&#x3002;&#x4E3A;&#x4E86;&#x66F4;&#x597D;&#x5730;&#x7406;&#x89E3;&#x57FA;&#x7840;&#x6027;&#x817A;&#x5F62;&#x6210;&#x7684;&#x673A;&#x5236;&#xFF0C;&#x6211;&#x4EEC;&#x5728;&#x679C;&#x8747;&#x4E2D;&#x6267;&#x884C;&#x8BF1;&#x53D8;&#x5C4F;&#x5E55;&#x5E76;&#x786E;&#x5B9A;&#x6240;&#x9700;&#x7684; gonadogenesis &#x7684;&#x4E8C;&#x5341;&#x56DB;&#x4E2A;&#x57FA;&#x56E0;&#x3002;&#x8FD9;&#x4E9B;&#x57FA;&#x56E0;&#x5F71;&#x54CD;&#x7684;&#x6027;&#x817A;&#x5F62;&#x6210;&#x7684;&#x5404;&#x4E2A;&#x4E0D;&#x540C;&#x65B9;&#x9762;&#xFF0C;&#x5E76;&#x63D0;&#x4F9B;&#x4E00;&#x4E2A;&#x6846;&#x67B6;&#xFF0C;&#x4E3A;&#x4E86;&#x89E3;&#x63A7;&#x5236;&#x8FD9;&#x4E9B;&#x8FDB;&#x7A0B;&#x7684;&#x5206;&#x5B50;&#x673A;&#x5236;&#x3002;&#x6211;&#x4EEC;&#x627E;&#x5230;&#x6027;&#x817A;&#x5F62;&#x6210;&#x53D7;&#x591A;&#x4E2A;&#x72EC;&#x7ACB;&#x7684;&#x8DEF;&#x5F84; &#xFF1B;&#x5176;&#x4E2D;&#x4E00;&#x4E9B;&#x89C4;&#x7BA1;&#x5173;&#x952E;&#x7EC6;&#x80DE;&#x7C98;&#x9644;&#x5206;&#x5B50;&#x5FB7;-&#x9499;&#x7C98;&#x86CB;&#x767D;&#xFF0C;&#x867D;&#x7136;&#x5176;&#x4ED6;&#x4EBA;&#x901A;&#x8FC7;&#x4E0D;&#x540C;&#x7684;&#x673A;&#x5236;&#x91C7;&#x53D6;&#x884C;&#x52A8;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x6211;&#x4EEC;&#x53D1;&#x73B0;&#x7F1D;/&#x56DE;&#x65CB;&#x5904;&#x7684;&#x901A;&#x8DEF;&#xFF0C;&#x4F01;&#x4E1A;&#x6700;&#x51FA;&#x540D;&#x7684;&#x662F;&#x5B83;&#x5728;&#x8C03;&#x8282;&#x8F74;&#x7A81;&#x7684;&#x6307;&#x5BFC;&#x4F5C;&#x7528;&#x662F;&#x9002;&#x5F53;&#x7684;&#x6027;&#x817A;&#x5F62;&#x6210;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#x3002;&#x6211;&#x4EEC;&#x7684;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#x63ED;&#x793A; gonadogenesis &#x548C;&#x6240;&#x9700;&#x7684;&#x9002;&#x5F53;&#x7684;&#x5668;&#x5B98;&#x5F62;&#x6210;&#x7684;&#x57FA;&#x56E0;&#x8C03;&#x63A7;&#x7684;&#x590D;&#x6742;&#x6027;&#x3002;

&#x5F71;&#x54CD;&#x6027;&#x817A;&#x5F62;&#x6210;&#x7684;&#x679C;&#x8747;&#x7A81;&#x53D8;&#x9057;&#x4F20;&#x5C4F;&#x663E;&#x7F1D;/robo &#x901A;&#x8DEF;&#x7684;&#x4F5C;&#x7528;&#x3002;

Organogenesis is a complex process requiring multiple cell types to associate with one another through correct cell contacts and in the correct location to achieve proper organ morphology and function. To better understand the mechanisms underlying gonad formation, we performed a mutagenesis screen in Drosophila and identified twenty-four genes required for gonadogenesis. These genes affect all different aspects of gonad formation and provide a framework for understanding the molecular mechanisms that control these processes. We find that gonad formation is regulated by multiple, independent pathways; some of these regulate the key cell adhesion molecule DE-cadherin, while others act through distinct mechanisms. In addition, we discover that the Slit/Roundabout pathway, best known for its role in regulating axonal guidance, is essential for proper gonad formation. Our findings shed light on the complexities of gonadogenesis and the genetic regulation required for proper organ formation.

A genetic screen for mutations affecting gonad formation in Drosophila reveals a role for the slit/robo pathway.

L&#39;organog&eacute;n&egrave;se est un processus complex qui exige plusieurs types de cellules &agrave; associer &agrave; un autre par le biais de contacts cellule correct et au bon endroit pour r&eacute;aliser la fonction et la morphologie de l&#39;organe appropri&eacute;. Pour mieux comprendre les m&eacute;canismes qui sous-tendent la formation de la gonade, nous avons effectu&eacute; un &eacute;cran de mutagen&egrave;se chez la drosophile et identifi&eacute; des vingt-quatre g&egrave;nes n&eacute;cessaires &agrave; gonadogenesis. Ces g&egrave;nes affectent tous les diff&eacute;rents aspects de la formation des gonades et fournissent un cadre pour comprendre les m&eacute;canismes mol&eacute;culaires qui contr&ocirc;lent ces processus. Nous trouvons que formation des gonades est r&eacute;gul&eacute;e par des voies multiples, ind&eacute;pendants ; certaines d&#39;entre elles r&eacute;gulent la mol&eacute;cule d&#39;adh&eacute;sion cellulaire cl&eacute; DE cadh&eacute;rine, tandis que d&#39;autres agissent par des m&eacute;canismes distincts. En outre, nous d&eacute;couvrons que la voie de la fente/rond-point, surtout connue pour son r&ocirc;le dans la r&eacute;gulation de guidage axonal, est essentielle pour la formation des gonades appropri&eacute;e. Nos constatations &eacute;clairent les complexit&eacute;s de la gonadogenesis et la r&eacute;gulation g&eacute;n&eacute;tique n&eacute;cessaire pour la formation des organes appropri&eacute;s.

Un d&eacute;pistage g&eacute;n&eacute;tique pour les mutations qui affectent la formation des gonades chez la drosophile r&eacute;v&egrave;le un r&ocirc;le pour la voie de la fente/robo.

Organogenese ist ein komplexer Prozess, dass mehrere Zelltypen miteinander zu verkn&uuml;pfen, durch richtige Zelle Kontakte und an der korrekten Position angemessene Orgel Morphologie und Funktion zu erreichen. Zum besseren Verst&auml;ndnis die Mechanismen Gonad Bildung zugrunde, die wir einen Mutagenese-Bildschirm in Drosophila durchgef&uuml;hrt und identifiziert vierundzwanzig-Gene, die f&uuml;r Gonadogenesis ben&ouml;tigt. Diese Gene betreffen alle verschiedenen Aspekte Gonad Formation und einen Rahmen f&uuml;r das Verst&auml;ndnis der molekularen Mechanismen, die diese Prozesse steuern. Wir finden, dass Gonad Bildung durch mehrere, unabh&auml;ngige Wege geregelt wird; Einige dieser Regeln die wichtigsten Zelladh&auml;sionsmolek&uuml;l DE-Cadherin, w&auml;hrend andere durch verschiedene Mechanismen handeln. Au&szlig;erdem entdecken wir, dass der Schlitz/Kreisverkehr Weg, am besten bekannt f&uuml;r seine Rolle bei der Regulierung axonale Anleitung f&uuml;r richtige Gonad Bildung wichtig. Unsere Erkenntnisse werfen Licht auf die Komplexit&auml;t der Gonadogenesis und die genetische Regulation zur richtigen Orgel Bildung erforderlich sind.

Ein genetischer Schirm f&uuml;r Mutationen Gonad-Formation in Drosophila zeigt eine Rolle f&uuml;r die Schlitz/Robo-Pathway.

Organogenesi sono un processo complesso che richiede pi&ugrave; tipi di cellule associare uno con l&#39;altro attraverso contatti cella corretta e la posizione corretta per realizzare la funzione e la morfologia del proprio organo. Per comprendere meglio i meccanismi sottostanti la formazione delle gonadi, abbiamo eseguito una schermata di mutagenesi in Drosophila e identificate venti-quattro geni necessari per gonadogenesis. Questi geni possono influenzare tutti i diversi aspetti della formazione delle gonadi e forniscono un quadro per la comprensione dei meccanismi molecolari che controllano questi processi. Troviamo che la formazione delle gonadi &egrave; regolata da percorsi multipli, indipendente; alcuni di questi regolano la molecola di adesione delle cellule chiave DE-caderina, mentre gli altri agiscono attraverso meccanismi distinti. Inoltre, scopriamo che il percorso fessura/rotonda, meglio conosciuto per il suo ruolo nella regolazione della guida assonale, &egrave; essenziale per la formazione delle gonadi adeguata. I nostri risultati fanno luce sulla complessit&agrave; del gonadogenesis e del regolamento genetico necessarie per la formazione del proprio organo.

Uno schermo genetico per le mutazioni che interessano la formazione delle gonadi in drosofila rivela un ruolo per il percorso fessura/robo.

&#x5668;&#x5B98;&#x5225;&#x306E;&#x6B63;&#x3057;&#x3044;&#x30BB;&#x30EB;&#x306E;&#x63A5;&#x89E6;&#x3092;&#x901A;&#x3058;&#x3066;&#x3001;&#x6B63;&#x3057;&#x3044;&#x5834;&#x6240;&#x306B;&#x9069;&#x5207;&#x306A;&#x81D3;&#x5668;&#x306E;&#x5F62;&#x614B;&#x3068;&#x6A5F;&#x80FD;&#x3092;&#x9054;&#x6210;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x308B;&#x306B;&#x306F;&#x8907;&#x6570;&#x306E;&#x30BB;&#x30EB;&#x306E;&#x7A2E;&#x985E;&#x3092;&#x5FC5;&#x8981;&#x3068;&#x3059;&#x308B;&#x8907;&#x96D1;&#x306A;&#x30D7;&#x30ED;&#x30BB;&#x30B9;&#x3067;&#x3059;&#x3002;&#x751F;&#x6B96;&#x817A;&#x5F62;&#x6210;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3092;&#x3088;&#x308A;&#x3088;&#x304F;&#x7406;&#x89E3;&#x3059;&#x308B;&#x306B;&#x306F;&#x3001;&#x30B7;&#x30E7;&#x30A6;&#x30B8;&#x30E7;&#x30A6;&#x30D0;&#x30A8;&#x306E;&#x7A81;&#x7136;&#x5909;&#x7570;&#x8A98;&#x767A;&#x30B9;&#x30AF;&#x30EA;&#x30FC;&#x30F3;&#x3092;&#x5B9F;&#x884C;&#x304A;&#x3088;&#x3073; gonadogenesis &#x306E;&#x305F;&#x3081;&#x306B;&#x5FC5;&#x8981;&#x306A; 20 4 &#x907A;&#x4F1D;&#x5B50;&#x3092;&#x8B58;&#x5225;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x306F;&#x751F;&#x6B96;&#x817A;&#x5F62;&#x6210;&#x306E;&#x3059;&#x3079;&#x3066;&#x306E;&#x3055;&#x307E;&#x3056;&#x307E;&#x306A;&#x5074;&#x9762;&#x306B;&#x5F71;&#x97FF;&#x3092;&#x4E0E;&#x3048;&#x308B;&#x3057;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E;&#x30D7;&#x30ED;&#x30BB;&#x30B9;&#x3092;&#x5236;&#x5FA1;&#x3059;&#x308B;&#x5206;&#x5B50;&#x6A5F;&#x69CB;&#x3092;&#x7406;&#x89E3;&#x3059;&#x308B;&#x305F;&#x3081;&#x306E;&#x30D5;&#x30EC;&#x30FC;&#x30E0;&#x30EF;&#x30FC;&#x30AF;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x307E;&#x3059;&#x3002;&#x751F;&#x6B96;&#x817A;&#x5F62;&#x6210;&#x304C;&#x8907;&#x6570;&#x306E;&#x72EC;&#x7ACB;&#x3057;&#x305F;&#x7D4C;&#x8DEF;&#x306B;&#x3088;&#x3063;&#x3066;&#x8ABF;&#x7BC0;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x3092;&#x898B;&#x3064;&#x3051;&#x308B;;&#x4ED6;&#x4EBA;&#x306F;&#x5225;&#x500B;&#x306E;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3092;&#x901A;&#x3058;&#x3066;&#x884C;&#x52D5;&#x3057;&#x306A;&#x304C;&#x3089;&#x3044;&#x304F;&#x3064;&#x304B;&#x3053;&#x308C;&#x3089;&#x306E;&#x30AD;&#x30FC;&#x306E;&#x7D30;&#x80DE;&#x63A5;&#x7740;&#x5206;&#x5B50;&#x30C7; &#x30AB;&#x30C9;&#x30D8;&#x30EA;&#x30F3;&#x3092;&#x8ABF;&#x7BC0;&#x3057;&#x307E;&#x3059;&#x3002;&#x307E;&#x305F;&#x3001;&#x30B9;&#x30EA;&#x30C3;&#x30C8;&#x306E;&#x30E9;&#x30A6;&#x30F3;&#x30C9; &#x30A2;&#x30D0;&#x30A6;&#x30C8;&#x306E;&#x7D4C;&#x8DEF;&#x306F;&#x3001;&#x6700;&#x9AD8;&#x306E;&#x8EF8;&#x7D22;&#x30AC;&#x30A4;&#x30C0;&#x30F3;&#x30B9;&#x3092;&#x5236;&#x5FA1;&#x306B;&#x304A;&#x3051;&#x308B;&#x305D;&#x306E;&#x5F79;&#x5272;&#x306E;&#x305F;&#x3081;&#x306B;&#x77E5;&#x3089;&#x308C;&#x3066;&#x9069;&#x5207;&#x306A;&#x751F;&#x6B96;&#x817A;&#x5F62;&#x6210;&#x306B;&#x4E0D;&#x53EF;&#x6B20;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x767A;&#x898B;&#x3057;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306E;&#x8ABF;&#x67FB;&#x7D50;&#x679C;&#x306F;&#x3001;gonadogenesis &#x3068;&#x9069;&#x5207;&#x306A;&#x81D3;&#x5668;&#x5F62;&#x6210;&#x306B;&#x5FC5;&#x8981;&#x306A;&#x907A;&#x4F1D;&#x7684;&#x5236;&#x5FA1;&#x306E;&#x8907;&#x96D1;&#x3055;&#x306B;&#x5149;&#x3092;&#x5F53;&#x3066;&#x307E;&#x3059;&#x3002;

&#x30B7;&#x30E7;&#x30A6;&#x30B8;&#x30E7;&#x30A6;&#x30D0;&#x30A8;&#x306E;&#x751F;&#x6B96;&#x817A;&#x5F62;&#x6210;&#x306B;&#x5F71;&#x97FF;&#x3092;&#x4E0E;&#x3048;&#x308B;&#x7A81;&#x7136;&#x5909;&#x7570;&#x306E;&#x907A;&#x4F1D;&#x306E;&#x753B;&#x9762;&#x306F;&#x3001;&#x30B9;&#x30EA;&#x30C3;&#x30C8;/&#x30ED;&#x30DC;&#x7D4C;&#x8DEF;&#x306E;&#x5F79;&#x5272;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x307E;&#x3059;&#x3002;

Organogenesis &#xD544;&#xC694;&#xD55C; &#xC5EC;&#xB7EC; &#xC138;&#xD3EC; &#xC720;&#xD615; &#xBC0F; &#xC801;&#xC808; &#xD55C; &#xAE30;&#xAD00;&#xC758; &#xD615;&#xD0DC;&#xC640; &#xAE30;&#xB2A5;&#xC744; &#xB2EC;&#xC131; &#xD558;&#xAE30; &#xC704;&#xD574; &#xC62C;&#xBC14;&#xB978; &#xC704;&#xCE58;&#xC5D0; &#xC62C;&#xBC14;&#xB978; &#xC140; &#xC811;&#xCD09;&#xC744; &#xD1B5;&#xD574; &#xC11C;&#xB85C; &#xC5F0;&#xACB0; &#xD558;&#xB294; &#xBCF5;&#xC7A1; &#xD55C; &#xACFC;&#xC815; &#xC774;&#xB2E4;. Gonad &#xD615;&#xC131;&#xC744; &#xAE30;&#xBCF8; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xB354; &#xC798; &#xC774;&#xD574; &#xD558;&#xAE30; &#xC6B0;&#xB9AC; &#xCD08;&#xD30C;&#xB9AC;&#xC5D0;&#xC11C; mutagenesis &#xD654;&#xBA74;&#xC744; &#xC218;&#xD589; &#xD558; &#xACE0; gonadogenesis&#xC5D0; &#xD544;&#xC694;&#xD55C; 24 &#xC720;&#xC804;&#xC790; &#xBC1C;&#xACAC;. &#xC774;&#xB7EC;&#xD55C; &#xC720;&#xC804;&#xC790; gonad &#xD615;&#xC131;&#xC758; &#xBAA8;&#xB4E0; &#xB2E4;&#xB978; &#xCE21;&#xBA74;&#xC5D0; &#xC601;&#xD5A5;&#xC744; &#xD558; &#xACE0; &#xC774;&#xB7EC;&#xD55C; &#xD504;&#xB85C;&#xC138;&#xC2A4;&#xB97C; &#xC81C;&#xC5B4; &#xD558;&#xB294; &#xBD84;&#xC790; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xC774;&#xD574; &#xD558;&#xAE30; &#xC704;&#xD55C; &#xD504;&#xB808;&#xC784; &#xC6CC;&#xD06C;&#xB97C; &#xC81C;&#xACF5; &#xD569;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xAC00; &#xCC3E;&#xC744; gonad &#xD615;&#xC131;&#xC740; &#xC5EC;&#xB7EC; &#xAC1C;&#xC758; &#xB3C5;&#xB9BD;&#xC801;&#xC778; &#xACBD;&#xB85C;;&#xC5D0; &#xC758;&#xD574; &#xADDC;&#xC81C; &#xC77C;&#xBD80;&#xB294; &#xC774;&#xB7EC;&#xD55C; &#xB2E4;&#xB978; &#xC11C;&#xB85C; &#xB2E4;&#xB978; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xD1B5;&#xD574; &#xC791;&#xB3D9; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xC8FC;&#xC694; &#xC138;&#xD3EC; &#xC811;&#xCC29; &#xBD84;&#xC790; &#xB4DC; cadherin &#xADDC;&#xC81C;. &#xB610;&#xD55C;, &#xC6B0;&#xB9AC; axonal &#xC9C0;&#xB3C4; &#xC870;&#xC808; &#xD558;&#xB294; &#xC5ED;&#xD560;&#xC5D0; &#xB300; &#xD55C; &#xAC00;&#xC7A5; &#xC798; &#xC54C;&#xB824;&#xC9C4; &#xC2AC;&#xB9BF;/&#xC6D0;&#xD615; &#xAD50;&#xCC28;&#xB85C; &#xD1B5;&#xB85C; &#xC801;&#xC808; &#xD55C; gonad &#xD615;&#xC131;&#xC744; &#xC704;&#xD574; &#xD544;&#xC218;&#xC801;&#xC785;&#xB2C8;&#xB2E4; &#xBC1C;&#xACAC;. &#xC6B0;&#xB9AC;&#xC758; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC; gonadogenesis &#xBC0F; &#xC801;&#xC808; &#xD55C; &#xAE30;&#xAD00; &#xD615;&#xC131;&#xC5D0; &#xD544;&#xC694;&#xD55C; &#xC720;&#xC804;&#xC790; &#xC870;&#xC808;&#xC758; &#xBCF5;&#xC7A1;&#xC131;&#xC5D0; &#xBE5B;&#xC744; &#xBC1C;&#xC0B0; &#xD569;&#xB2C8;&#xB2E4;.

&#xB3CC;&#xC5F0;&#xBCC0;&#xC774; &#xCD08;&#xD30C;&#xB9AC;&#xC5D0;&#xC11C; gonad &#xD615;&#xC131;&#xC5D0; &#xC601;&#xD5A5;&#xC744; &#xBBF8;&#xCE58;&#xB294; &#xB300; &#xD55C; &#xC720;&#xC804;&#xC790; &#xD654;&#xBA74; &#xC2AC;&#xB9BF;/&#xB85C; &#xBCF4; &#xD1B5;&#xB85C; &#xC5ED;&#xD560;&#xC744; &#xBCF4;&#xC5EC;&#xC900;&#xB2E4;.

Organog&eacute;nesis es un proceso complejo que requiere m&uacute;ltiples tipos de c&eacute;lulas asociar entre s&iacute; a trav&eacute;s de contacto correcta y en el lugar correcto para lograr la funci&oacute;n y morfolog&iacute;a del &oacute;rgano adecuado. Para comprender mejor los mecanismos que subyacen a la formaci&oacute;n de la g&oacute;nada, realizamos una pantalla de mutag&eacute;nesis en Drosophila e identific&oacute; veinticuatro genes necesarios para gonadogenesis. Estos genes afectan todos los aspectos diferentes de la formaci&oacute;n de la g&oacute;nada y proporcionan un marco para entender los mecanismos moleculares que controlan estos procesos. Encontramos que la formaci&oacute;n de la g&oacute;nada est&aacute; regulada por m&uacute;ltiples v&iacute;as independientes; algunos de estos regulan la mol&eacute;cula de adhesi&oacute;n celular clave DE-cadherina, mientras que otros act&uacute;an a trav&eacute;s de distintos mecanismos. Adem&aacute;s, descubrimos que la v&iacute;a de la hendidura/rotonda, mejor conocida por su papel en la regulaci&oacute;n de la gu&iacute;a axonal, es esencial para la formaci&oacute;n de la g&oacute;nada apropiada. Nuestros resultados arrojan luz sobre la complejidad de la gonadogenesis y la regulaci&oacute;n gen&eacute;tica necesaria para la formaci&oacute;n del &oacute;rgano adecuado.

Una pantalla gen&eacute;tica para las mutaciones que afectan a la formaci&oacute;n de la g&oacute;nada en Drosophila revela un papel para la v&iacute;a de la hendidura/robo.

Coronary plaque morphology, including plaque size and fibrous cap thickness, is thought to contribute to the risk of plaque rupture and future cardiac events. Dual-frequency intravascular ultrasound has been proposed as a possible technique to visualize both large-scale features and superficial detail of coronary plaque; however, it has not been found to be feasible within the constraints of a clinically functional intravascular ultrasound catheter. In this study, we describe the design and fabrication of a dual-frequency catheter using a bidirectional transducer stack with center frequencies of approximately 30 and 80 MHz. We describe how the high-frequency transducer achieves significantly improved axial and lateral resolution (16 and 120 µm, respectively, vs. 50 and 220 µm) at the expense of penetration depth. Finally, imaging of ex vivo human coronary artery segments reveals that the catheter can provide complementary images of the deeper arterial wall and superficial plaque features.

Development of a 3 French Dual-Frequency Intravascular Ultrasound Catheter.

As lipid composition of atherosclerotic plaques is considered to be one of the primary indicators for plaque vulnerability, a diagnostic modality that can sensitively evaluate their necrotic core is highly desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection modality that provides lipid-specific chemical information of arterial walls. Within the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications because lipid exhibits a strong absorption peak at that wavelength. However, other arterial tissues also show some degree of absorption near 1210 nm and generate undesirable interfering PA signals. In this study, a novel wavelength-modulated Intravascular Differential Photoacoustic Radar (IV-DPAR) modality was introduced as an interference-free detection technique for a more accurate and reliable diagnosis of plaque progression. By using two low-power continuous-wave laser diodes in a differential manner, IV-DPAR could efficiently suppress undesirable absorptions and system noise, while dramatically improving system sensitivity and specificity to cholesterol, the primary ingredient of plaque necrotic core. When co-registered with intravascular ultrasound imaging, IV-DPAR could sensitively locate and characterize the lipid contents of plaques in human atherosclerotic arteries, regardless of their size and depth.

Interference-free Detection of Lipid-laden Atherosclerotic Plaques by 3D Co-registration of Frequency-Domain Differential Photoacoustic and Ultrasound Radar Imaging.

Intramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia-reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent a reperfused AMI procedure: control and DFP treated (N = 7 each). A comprehensive MRI examination was performed in healthy state and up to week 4 post-AMI, followed by histological assessment. Infarct size was not significantly different between the two groups; however, the DFP group demonstrated earlier resolution of hemorrhage (by T2* imaging) and edema (by T2 imaging). Additionally, ventricular enlargement and myocardial hypertrophy (wall thickness and mass) were significantly smaller with DFP, suggesting reduced adverse remodeling, compared to control. The histologic results were consistent with the MRI findings. To date, there is no effective targeted therapy for reperfusion hemorrhage. Our proof-of-concept study is the first to identify hemorrhage-derived iron as a therapeutic target in I/R and exploit the cardioprotective properties of an iron-chelating drug candidate in the setting of AMI. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI.

Action of iron chelator on intramyocardial hemorrhage and cardiac remodeling following acute myocardial infarction.

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant β-values >7). Myocardial oxygen consumption had almost no effect on T2 (β-values <0.002); since PvO is influenced by both oxygen consumption and MBF, PvO changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO and MBV confirmed that PvO had the strongest influence on T2, but MBV became important at high PvO . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.

ArticleTotal : 2	Year
Publication title Cited by 23	2012
Publication title	2023

Article	Year
The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 12122205	2002
A genetic screen for mutations affecting gonad formation in Drosophila reveals a role for the slit/robo pathway. Developmental biology\| PubMed ID: 21377458	2011
Development of a 3 French Dual-Frequency Intravascular Ultrasound Catheter. Ultrasound in medicine & biology\| PubMed ID: 29150363
Interference-free Detection of Lipid-laden Atherosclerotic Plaques by 3D Co-registration of Frequency-Domain Differential Photoacoustic and Ultrasound Radar Imaging. Scientific reports\| PubMed ID: 31455883
Action of iron chelator on intramyocardial hemorrhage and cardiac remodeling following acute myocardial infarction. Basic research in cardiology\| PubMed ID: 32140789
Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2. NMR in biomedicine\| PubMed ID: 34791720	2022

Jill J. Weyers

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