a-lateralized-odor-learning-model-neonatal-rats-for-dissecting-neural

A Lateralized Odor Learning Model in Neonatal Rats for Dissecting Neural Circuitry Underpinning Memory Formation

Rat pups during a critical postnatal period (&#8804; 10 days) readily form a preference for an odor that is associated with stimuli mimicking maternal ...

Prion Safety Laboratory Swipe Test

Transmission of iatrogenic prion disease has occurred from contaminated neurosurgical tools, transplant materials, and occupational exposure to ...

Faculty of Medicine, Memorial University

Creighton University

&#x670A;&#x75C5;&#x6BD2;&#x4E0E;&#x571F;&#x58E4;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x53EF;&#x80FD;&#x6162;&#x6027;&#x6D88;&#x8017;&#x6027;&#x75BE;&#x75C5; (CWD) &#x548C;&#x7EF5;&#x7F8A;&#x75D2;&#x75C5;&#x7684;&#x4F20;&#x64AD;&#x4E2D;&#x53D1;&#x6325;&#x91CD;&#x8981;&#x4F5C;&#x7528;&#x3002;&#x670A;&#x75C5;&#x6BD2;&#x5DF2;&#x77E5;&#x7ED1;&#x5B9A;&#x5230;&#x5404;&#x79CD;&#x5404;&#x6837;&#x7684;&#x571F;&#x58E4;&#x8868;&#x9762;&#xFF0C;&#x4F46;&#x5438;&#x9644;&#x6EB6;&#x6DB2;&#x5316;&#x5B66;&#x7684;&#x5F71;&#x54CD;&#xFF0C;&#x5BF9;&#x670A;&#x75C5;&#x6BD2;&#x7684;&#x547D;&#x8FD0;&#x548C;&#x4F20;&#x8F93;&#x98CE;&#x9669;&#x957F;&#x671F;&#x571F;&#x58E4;&#x5177;&#x6709;&#x7EA6;&#x675F;&#x529B;&#x7684;&#x662F;&#x672A;&#x77E5;&#x3002;&#x6211;&#x4EEC;&#x8C03;&#x67E5; HY TME &#x670A;&#x86CB;&#x767D; (PrP(Sc)) &#x5438;&#x9644;&#x5230;&#x571F;&#x58E4;&#x77FF;&#x7269;&#x5728;&#x6C34;&#x6EB6;&#x6DB2;&#x7684;&#x78F7;&#x9178;&#x7F13;&#x51B2;&#x76D0;&#x6C34; (PBS)&#x3001; &#x6C2F;&#x5316;&#x94A0;&#x3001; &#x6C2F;&#x5316;&#x9499;&#x548C;&#x53BB;&#x79BB;&#x5B50;&#x7684;&#x6C34;&#x4F7F;&#x7528;&#x514D;&#x75AB;&#x5370;&#x8FF9;&#x3002;&#x7531;&#x86CB;&#x767D;&#x8D28;&#x6298;&#x53E0;&#x5FAA;&#x73AF;&#x6269;&#x589E; (PMCA)&#xFF0C;&#x8FD8;&#x8BC4;&#x4EF7;&#x4E86;&#x540E;&#x5438;&#x9644;&#x5728;&#x8FD9;&#x4E9B;&#x89E3;&#x51B3;&#x65B9;&#x6848;&#x4E2D;&#x7684;&#x7ED1;&#x5B9A;&#x670A;&#x75C5;&#x6BD2;&#x7684;&#x590D;&#x5236;&#x6548;&#x7387;&#x3002;&#x8001;&#x5316;&#x7814;&#x7A76;&#x4E00;&#x5E74;&#x540E; PBS &#x6216;&#x53BB;&#x79BB;&#x5B50;&#x6C34;&#x4E2D;&#x7684;&#x5438;&#x9644;&#x5230;&#x8C03;&#x67E5; PrP(Sc) &#x89E3;&#x5438;&#x548C;&#x590D;&#x5236;&#x6548;&#x7387;&#x4E86;&#x3002;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x5438;&#x9644;&#x6EB6;&#x6DB2;&#x5316;&#x5B66;&#x53EF;&#x4EE5;&#x5F71;&#x54CD;&#x968F;&#x540E;&#x670A;&#x75C5;&#x6BD2;&#x590D;&#x5236;&#x6216;&#x89E3;&#x5438;&#x7684;&#x80FD;&#x529B;&#xFF0C;&#x5C24;&#x5176;&#x662F;&#x540E; 30 d &#x6216;&#x66F4;&#x957F;&#x7684;&#x6F5C;&#x4F0F;&#x671F;&#x3002;&#x89C2;&#x5BDF;&#x5230;&#x7684;&#x5F71;&#x54CD;&#x662F;&#x8F7B;&#x5FAE;&#x77ED;&#x671F; (7 d &#x6216;&#x66F4;&#x5C11;&#xFF09;&#x3002;&#x957F;&#x671F;&#x8001;&#x5316;&#x5B9E;&#x9A8C;&#x7684;&#x7ED3;&#x679C;&#x8BC1;&#x660E;&#x672A;&#x7ED1;&#x5B9A;&#x670A;&#x75C5;&#x6BD2;&#x6216;&#x7ED1;&#x5B9A;&#x5230;&#x5404;&#x79CD;&#x4E0D;&#x540C;&#x7684;&#x571F;&#x58E4;&#x8868;&#x9762;&#x7684;&#x670A;&#x75C5;&#x6BD2;&#x4E00;&#x5E74;&#x540E;&#x53EF;&#x4EE5;&#x8F7B;&#x6613;&#x590D;&#x5236;&#x3002;&#x6211;&#x4EEC;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x867D;&#x7136;&#x670A;&#x75C5;&#x6BD2;-&#x571F;&#x58E4;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x53EF;&#x4EE5;&#x968F;&#x6EB6;&#x6DB2;&#x5316;&#x5B66;&#xFF0C;&#x7ED1;&#x5B9A;&#x5230;&#x571F;&#x58E4;&#x7684;&#x670A;&#x75C5;&#x6BD2;&#x53EF;&#x80FD;&#x4ECD;&#x7136;&#x4F20;&#x8F93;&#x540E;&#x51E0;&#x4E2A;&#x6708;&#x5728;&#x73AF;&#x5883;&#x4E2D;&#x7684;&#x670A;&#x75C5;&#x6BD2;&#x75BE;&#x75C5;&#x7684;&#x98CE;&#x9669;&#x3002;

&#x5BF9;&#x670A;&#x86CB;&#x767D;&#x5438;&#x9644;&#x548C;&#x571F;&#x58E4;&#x7ED1;&#x5B9A;&#x670A;&#x75C5;&#x6BD2;&#x7684;&#x590D;&#x5236;&#x89E3;&#x51B3;&#x65B9;&#x6848;&#x5316;&#x5B66;&#x548C;&#x8001;&#x5316;&#x65F6;&#x95F4;&#x7684;&#x5F71;&#x54CD;&#x3002;

Prion interactions with soil may play an important role in the transmission of chronic wasting disease (CWD) and scrapie. Prions are known to bind to a wide range of soil surfaces, but the effects of adsorption solution chemistry and long-term soil binding on prion fate and transmission risk are unknown. We investigated HY TME prion protein (PrP(Sc)) adsorption to soil minerals in aqueous solutions of phosphate buffered saline (PBS), sodium chloride, calcium chloride, and deionized water using western blotting. The replication efficiency of bound prions following adsorption in these solutions was also evaluated by protein misfolding cyclic amplification (PMCA). Aging studies investigated PrP(Sc) desorption and replication efficiency up to one year following adsorption in PBS or DI water. Results indicate that adsorption solution chemistry can affect subsequent prion replication or desorption ability, especially after incubation periods of 30 d or longer. Observed effects were minor over the short-term (7 d or less). Results of long-term aging experiments demonstrate that unbound prions or prions bound to a diverse range of soil surfaces can readily replicate after one year. Our results suggest that while prion-soil interactions can vary with solution chemistry, prions bound to soil could remain a risk for transmitting prion diseases after months in the environment.

Effects of solution chemistry and aging time on prion protein adsorption and replication of soil-bound prions.

Interactions de prion avec sol peuvent jouer un r&ocirc;le important dans la transmission de la maladie d&eacute;bilitante chronique (MDC) et de la tremblante. Prions sont connues pour lier &agrave; un large &eacute;ventail de la surface du sol, mais les effets de la chimie en solution adsorption et liaison de sol &agrave; long terme sur le risque de sort et de transmission de prion sont inconnus. Nous avons &eacute;tudi&eacute; la prot&eacute;ine prion HY TME (PrP(Sc)) adsorption sur les min&eacute;raux du sol dans des solutions aqueuses d&#39;en solution saline tamponn&eacute;e au phosphate (PBS), chlorure de sodium, chlorure de calcium et l&#39;eau d&eacute;ionis&eacute;e &agrave; l&#39;aide de western blot. L&#39;efficacit&eacute; de la r&eacute;plication des prions li&eacute;es apr&egrave;s adsorption dans ces solutions a &eacute;galement &eacute;t&eacute; &eacute;valu&eacute;e par la prot&eacute;ine misfolding cyclique amplification (PMCA). &Eacute;tudes de vieillissement &eacute;tudi&eacute; PrP(Sc) d&eacute;sorption et r&eacute;plication efficacit&eacute; jusqu&#39;&agrave; un an apr&egrave;s adsorption dans PBS ou DI l&#39;eau. Les r&eacute;sultats indiquent que chimie solution adsorption peut affecter la capacit&eacute; de r&eacute;plication ou d&eacute;sorption de prion ult&eacute;rieurs, surtout apr&egrave;s des p&eacute;riodes d&#39;incubation de 30 jours ou plus. Effets observ&eacute;s &eacute;taient mineures sur le court terme (7 d ou moins). Les r&eacute;sultats des exp&eacute;riences de vieillissement &agrave; long terme montrent que les prions non li&eacute;es ou prions li&eacute;es &agrave; une gamme vari&eacute;e de la surface du sol peuvent facilement reproduire apr&egrave;s un an. Nos r&eacute;sultats sugg&egrave;rent que, tandis que des interactions sol-prion peuvent varier selon la chimie en solution, prions li&eacute;es au sol pourraient rester un risque de transmission de maladies &agrave; prions apr&egrave;s des mois dans l&#39;environnement.

Effets du temps de vieillissement et de la chimie solution sur l&#39;adsorption de prot&eacute;ine prion et r&eacute;plication des sols li&eacute;s aux prions.

Prion Interaktionen mit Boden k&ouml;nnen eine wichtige Rolle bei der &Uuml;bertragung der chronic wasting Disease (CWD) und Scrapie. Prionen sind zum Binden an eine Vielzahl von Boden-Oberfl&auml;chen, aber die Auswirkungen der Adsorption L&ouml;sung Chemie bekannt und langfristige Boden-Bindung auf das Prion Schicksal und &Uuml;bertragung Risiko sind unbekannt. Wir untersuchten HY TME Prionprotein (PrP(Sc)) Adsorption an den Boden Mineralien in w&auml;ssrigen L&ouml;sungen von phosphatgepufferter Kochsalzl&ouml;sung (PBS), Natriumchlorid, Calciumchlorid und entsalztem Wasser mit westlichen Beflecken. Die Replikationseffizienz von gebundenen Prionen nach Adsorption in diesen L&ouml;sungen wurde auch von Protein misfolding cyclic Amplification (PMCA) evaluiert. Alterung Studien untersucht PrP(Sc) Desorption und Replikation Effizienz bis zu einem Jahr nach Adsorption in PBS oder DI-Wasser. Ergebnisse zeigen, dass Adsorption L&ouml;sung Chemie nachfolgende Prion-Replikation oder Desorption, vor allem nach Inkubationszeiten von 30D oder l&auml;nger beeintr&auml;chtigen kann. Beobachteten Effekte waren geringf&uuml;gig &uuml;ber dem kurzfristigen (7 d oder weniger). Ergebnisse langfristig alternden Experimente belegen, dass die ungebundenen Prionen oder Prionen verpflichtet, ein breites Spektrum von Boden-Oberfl&auml;chen leicht nach einj&auml;hriger replizieren k&ouml;nnen. Unsere Ergebnisse legen nahe, dass w&auml;hrend Prion-Boden Interaktionen zwischen L&ouml;sung Chemie variiert, Prionen, die an die Erde gebunden ein Risiko f&uuml;r die &Uuml;bertragung von Prionenkrankheiten nach Monaten in der Umgebung bleiben konnte.

Auswirkungen der L&ouml;sungszeit Chemie und Alterung auf Prion Proteinadsorption und Replikation von Prionen Boden gebunden.

Interazioni prionica con terreno possono svolgere un ruolo importante nella trasmissione della malattia del dimagrimento cronico (CWD) e della scrapie. I prioni sono noti per associare a una vasta gamma di superfici di terreno, ma gli effetti della chimica soluzione adsorbimento e associazione del suolo a lungo termine sul rischio di destino e trasmissione di prioni sono sconosciuti. Abbiamo studiato la proteina prionica HY TME (PrP(Sc)) assorbimento di minerali del suolo in soluzioni acquose di tampone fosfato salino (PBS), cloruro di sodio, cloruro di calcio e acqua deionizzata mediante western blotting. L&#39;efficienza di replicazione dei prioni associati dopo adsorbimento in queste soluzioni &egrave; stata valutata anche dalla proteina misfolding amplificazione ciclico (IVETTE). Studi di invecchiamento indagato l&#39;efficienza di replica e di desorbimento PrP(Sc) fino ad un anno successivo adsorbimento in PBS o DI acqua. I risultati indicano che chimica soluzione adsorbimento pu&ograve; interessare prione successiva replica o desorbimento capacit&agrave;, soprattutto dopo periodi di incubazione di 30 d o pi&ugrave;. Gli effetti osservati erano minori oltre il breve termine (7 d o meno). Risultati di esperimenti di invecchiamento a lungo termine dimostrano che i prioni non associati o prioni associati a una vasta gamma di superfici di terreno possono replicare prontamente dopo un anno. I nostri risultati suggeriscono che, mentre le interazioni del prione-terreno possono variare con la chimica in soluzione, prioni associati al suolo potrebbero rimanere un rischio per la trasmissione di malattie da prioni dopo mesi nell&#39;ambiente.

Effetti della soluzione chimica e invecchiamento tempo sull&#39;adsorbimento della proteina prionica e replica del suolo associato prioni.

&#x571F;&#x58CC;&#x3068;&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x304C;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x306F;&#x6162;&#x6027;&#x6D88;&#x8017;&#x6027;&#x75BE;&#x60A3; (CWD) &#x3068;&#x30B9;&#x30AF;&#x30EC;&#x30A4;&#x30D4;&#x30FC;&#x306E;&#x4F1D;&#x9001;&#x306B;&#x518D;&#x751F;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x306E;&#x571F;&#x58CC;&#x8868;&#x9762;&#x5438;&#x7740;&#x6EB6;&#x6DB2;&#x5316;&#x5B66;&#x306E;&#x5F71;&#x97FF;&#x304C;&#x5E83;&#x3044;&#x7BC4;&#x56F2;&#x306B;&#x30D0;&#x30A4;&#x30F3;&#x30C9;&#x3059;&#x308B;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x3057;&#x3001;&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x306E;&#x904B;&#x547D;&#x3068;&#x4F1D;&#x9001;&#x30EA;&#x30B9;&#x30AF;&#x306B;&#x95A2;&#x3059;&#x308B;&#x9577;&#x671F;&#x571F;&#x58CC;&#x30D0;&#x30A4;&#x30F3;&#x30C7;&#x30A3;&#x30F3;&#x30B0;&#x306F;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F; HY TME &#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x86CB;&#x767D;&#x8CEA; (&#x30A6;&#x30A8;&#x30B9;&#x30BF;&#x30F3;&#x30D6;&#x30ED;&#x30C3;&#x30C8;&#x6CD5;&#x3092;&#x7528;&#x3044;&#x305F;&#x8131;&#x30A4;&#x30AA;&#x30F3;&#x6C34;&#x3001;&#x5869;&#x5316;&#x30AB;&#x30EB;&#x30B7;&#x30A6;&#x30E0;&#x3001;&#x5869;&#x5316;&#x30CA;&#x30C8;&#x30EA;&#x30A6;&#x30E0;&#x3001;&#x30EA;&#x30F3;&#x9178;&#x7DE9;&#x885D;&#x751F;&#x7406;&#x98DF;&#x5869;&#x6C34; &#xFF08;PBS&#xFF09; &#x306E;&#x6C34;&#x6EB6;&#x6DB2;&#x4E2D;&#x3067;&#x306E;&#x571F;&#x58CC;&#x9271;&#x7269;&#x3078;&#x306E; PrP(Sc)) &#x5438;&#x7740;&#x3002; &#x3092;&#x8ABF;&#x3079;&#x305F;&#x30D0;&#x30A4;&#x30F3;&#x30C9;&#x3055;&#x308C;&#x305F;&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x5438;&#x7740;&#x3053;&#x308C;&#x3089;&#x306E;&#x30BD;&#x30EA;&#x30E5;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x3067;&#x3001;&#x6B21;&#x306E;&#x30EC;&#x30D7;&#x30EA;&#x30B1;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x306E;&#x52B9;&#x7387;&#x306F;&#x307E;&#x305F;&#x7E70;&#x8FD4;&#x3057;&#x5897;&#x5E45; &#xFF08;PMCA&#xFF09; &#x7570;&#x5E38;&#x6298;&#x308A;&#x7573;&#x307F;&#x86CB;&#x767D;&#x8CEA;&#x306B;&#x3088;&#x3063;&#x3066;&#x8A55;&#x4FA1;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x7814;&#x7A76;&#x3092;&#x30A8;&#x30FC;&#x30B8;&#x30F3;&#x30B0; prp (sc) &#x306E;&#x8131;&#x7740;&#x304A;&#x3088;&#x3073;&#x30EC;&#x30D7;&#x30EA;&#x30B1;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x306E;&#x52B9;&#x7387;&#x3092; 1 &#x5E74;&#x6B21;&#x306E;&#x5438;&#x7740; PBS &#x307E;&#x305F;&#x306F; DI &#x6C34;&#x3067;&#x8ABF;&#x67FB;&#x3057;&#x307E;&#x3059;&#x3002;&#x7D50;&#x679C;&#x306F;&#x3001;&#x5438;&#x7740;&#x6EB6;&#x6DB2;&#x5316;&#x5B66;&#x6F5C;&#x4F0F;&#x671F;&#x9593;&#x4EE5;&#x4E0A; 30 d &#x306E;&#x5F8C;&#x7279;&#x306B;&#x5F8C;&#x7D9A;&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x8907;&#x88FD;&#x307E;&#x305F;&#x306F;&#x8131;&#x96E2;&#x80FD;&#x529B;&#x306B;&#x5F71;&#x97FF;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x89B3;&#x5BDF;&#x3055;&#x308C;&#x305F;&#x5F71;&#x97FF;&#x306F;&#x77ED;&#x671F; (7 &#x4EE5;&#x4E0A; d &#x307E;&#x305F;&#x306F;&#x5C11;&#x306A;&#x3044;&#xFF09; &#x306F;&#x8EFD;&#x5FAE;&#x3067;&#x3042;&#x3063;&#x305F;&#x3002;&#x9577;&#x671F;&#x7684;&#x306A;&#x9AD8;&#x9F62;&#x5316;&#x5B9F;&#x9A13;&#x306E;&#x7D50;&#x679C;&#x306F;&#x3001;&#x975E;&#x9023;&#x7D50;&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x307E;&#x305F;&#x306F;&#x571F;&#x58CC;&#x8868;&#x9762;&#x306E;&#x591A;&#x69D8;&#x306A;&#x7BC4;&#x56F2;&#x306B;&#x30D0;&#x30A4;&#x30F3;&#x30C9; &#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x304C; 1 &#x5E74;&#x5F8C;&#x5BB9;&#x6613;&#x306B;&#x8907;&#x88FD;&#x3067;&#x304D;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x3068;&#x571F;&#x58CC;&#x306E;&#x76F8;&#x4E92;&#x6EB6;&#x6DB2;&#x5316;&#x5B66;&#x3068;&#x5909;&#x308F;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x308B;&#x9593;&#x3001;&#x571F;&#x306B;&#x30D0;&#x30A4;&#x30F3;&#x30C9; &#x30D7;&#x30EA;&#x30AA;&#x30F3; &#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x75C5;&#x74B0;&#x5883;&#x3067;&#x6570;&#x30F6;&#x6708;&#x5F8C;&#x9001;&#x4FE1;&#x3059;&#x308B;&#x305F;&#x3081;&#x3001;&#x30EA;&#x30B9;&#x30AF;&#x304C;&#x6B8B;&#x308B;&#x3053;&#x3068;&#x306F;&#x793A;&#x5506;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;

&#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x86CB;&#x767D;&#x8CEA;&#x5438;&#x7740;&#x3068;&#x571F;&#x58CC;&#x30D0;&#x30A4;&#x30F3;&#x30C9; &#x30D7;&#x30EA;&#x30AA;&#x30F3;&#x306E;&#x30EC;&#x30D7;&#x30EA;&#x30B1;&#x30FC;&#x30B7;&#x30E7;&#x30F3; &#x30BD;&#x30EA;&#x30E5;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x5316;&#x5B66;&#x3068;&#x6642;&#x52B9;&#x6642;&#x9593;&#x306E;&#x5F71;&#x97FF;

&#xD504;&#xB9AC;&#xC628; &#xC0C1;&#xD638; &#xD1A0;&#xC591; &#xB9CC;&#xC131; &#xB0AD;&#xBE44; &#xC9C8;&#xD658; (CWD)&#xACFC; scrapie&#xC758; &#xC804;&#xC1A1; &#xC911;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xC7AC;&#xC0DD;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xB2E4;&#xC591; &#xD55C; &#xC194;&#xB8E8;&#xC158; &#xD654;&#xD559; &#xD761;&#xCC29;&#xC758; &#xD6A8;&#xACFC; &#xD558;&#xC9C0;&#xB9CC; &#xD1A0;&#xC591; &#xD45C;&#xBA74;&#xC5D0; &#xBC14;&#xC778;&#xB529;&#xD560; prions &#xC54C;&#xB824;&#xC838; &#xC788;&#xC73C;&#xBA70; &#xD504;&#xB9AC;&#xC628;&#xC758; &#xC6B4;&#xBA85;&#xACFC; &#xC804;&#xC1A1; &#xC704;&#xD5D8;&#xC5D0; &#xC7A5;&#xAE30;&#xC801;&#xC778; &#xD1A0;&#xC591; &#xBC14;&#xC778;&#xB529; &#xC54C;&#xB824;&#xC9C0;&#xC9C0; &#xC54A;&#xC740;. &#xC6B0;&#xB9AC; &#xC870;&#xC0AC; HY TME &#xD504;&#xB9AC;&#xC628; &#xB2E8;&#xBC31;&#xC9C8; (PrP(Sc)) &#xBC84;&#xD37C;&#xB9C1; &#xC778;&#xC0B0; &#xC5FC; (PBS), &#xC5FC;&#xD654; &#xB098;&#xD2B8;&#xB968;, &#xCE7C;&#xC298; &#xC5FC;&#xD654; &#xBB3C;, &#xADF8;&#xB9AC;&#xACE0; &#xC11C;&#xCABD;&#xC5D0; &#xAC8C; &#xB354; &#xB7FD; &#xD788;&#xAE30;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xC774;&#xC628;&#xB41C; &#xC218;&#xC758; &#xC218;&#xC131; &#xC194;&#xB8E8;&#xC158;&#xC5D0; &#xD1A0;&#xC591; &#xBBF8;&#xB124;&#xB784;&#xC744; &#xD761;&#xCC29;. &#xC774;&#xB7EC;&#xD55C; &#xC194;&#xB8E8;&#xC158;&#xC5D0;&#xB294; &#xD761;&#xCC29;&#xC5D0; &#xB530;&#xB77C; &#xBC14;&#xC6B4;&#xB4DC; prions &#xBCF5;&#xC81C; &#xD6A8;&#xC728;&#xC131; &#xB610;&#xD55C; &#xC21C;&#xD658; &#xC99D;&#xD3ED; (PMCA) misfolding &#xB2E8;&#xBC31;&#xC9C8;&#xC5D0; &#xC758;&#xD574; &#xD3C9;&#xAC00; &#xBC1B;&#xC558;&#xB2E4;. &#xB178;&#xD654; &#xC5F0;&#xAD6C; PBS &#xB610;&#xB294; &#xB514; &#xBB3C;&#xC5D0; &#xD761;&#xCC29;&#xC5D0; &#xB530;&#xB77C; 1 &#xB144;&#xC5D0; &#xCD5C;&#xB300; PrP(Sc) &#xD0C8; &#xCC29; &#xBC0F; &#xBCF5;&#xC81C; &#xD6A8;&#xC728;&#xC131; &#xC870;&#xC0AC;. &#xACB0;&#xACFC; 30 d &#xC774;&#xC0C1; &#xBD80; &#xD654; &#xAE30;&#xAC04; &#xD6C4;&#xC5D0; &#xD2B9;&#xD788; &#xD6C4;&#xC18D; &#xD504;&#xB9AC;&#xC628; &#xBCF5;&#xC81C; &#xB610;&#xB294; &#xD0C8; &#xCC29; &#xAE30;&#xB2A5;, &#xD761;&#xCC29; &#xC194;&#xB8E8;&#xC158; &#xD654;&#xD559; &#xC218;&#xC5D0; &#xC601;&#xD5A5;&#xC744; &#xB098;&#xD0C0;&#xB0C5;&#xB2C8;&#xB2E4;. &#xAD00;&#xCC30; &#xB41C; &#xD6A8;&#xACFC; &#xB2E8;&#xAE30; (7 d &#xC774;&#xD558;&#xC758;) &#xC0AC;&#xC18C;&#xD55C; &#xD588;&#xB2E4;. &#xC7A5;&#xAE30; &#xB178;&#xD654; &#xC2E4;&#xD5D8; &#xACB0;&#xACFC; &#xC785;&#xC99D; &#xC5B8;&#xBC14;&#xC6B4;&#xB4DC; prions &#xB610;&#xB294; &#xB2E4;&#xC591; &#xD55C; &#xD1A0;&#xC591; &#xD45C;&#xBA74;&#xC5D0; &#xBC14;&#xC778;&#xB529;&#xB41C; prions &#xC77C;&#xB144; &#xD6C4; &#xC27D;&#xAC8C; &#xBCF5;&#xC81C;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xC758; &#xACB0;&#xACFC; &#xD504;&#xB9AC;&#xC628;-&#xD1A0;&#xC591;&#xC758; &#xC0C1;&#xD638; &#xC791;&#xC6A9; &#xC194;&#xB8E8;&#xC158; &#xD654;&#xD559;&#xC73C;&#xB85C; &#xB2E4;&#xB97C; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;, &#xD1A0;&#xC591;&#xC5D0; &#xBC14;&#xC778;&#xB529;&#xB41C; prions &#xD658;&#xACBD;&#xC5D0;&#xC11C; &#xAC1C;&#xC6D4; &#xD6C4; &#xD504;&#xB9AC;&#xC628; &#xC9C8;&#xBCD1;&#xC744; &#xC804;&#xC1A1; &#xD558;&#xAE30; &#xC704;&#xD55C; &#xC704;&#xD5D8; &#xC720;&#xC9C0; &#xC218; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xD504;&#xB9AC;&#xC628; &#xB2E8;&#xBC31;&#xC9C8; &#xD761;&#xCC29;&#xC5D0; &#xD1A0;&#xC591; &#xBC14;&#xC778;&#xB529;&#xB41C; prions &#xBCF5;&#xC81C; &#xC194;&#xB8E8;&#xC158; &#xD654;&#xD559; &#xBC0F; &#xB178;&#xD654; &#xC2DC;&#xAC04; &#xD6A8;&#xACFC;.

Interacciones del pri&oacute;n con suelo pueden jugar un papel importante en la transmisi&oacute;n de la caquexia cr&oacute;nica (CWD) y de la tembladera. Los priones son conocidos para enlazar a una amplia gama de superficies de tierra, pero los efectos de la qu&iacute;mica de soluci&oacute;n de adsorci&oacute;n y vinculante de suelo a largo plazo sobre el riesgo de destino y transmisi&oacute;n del pri&oacute;n son desconocidos. Investigamos la prote&iacute;na pri&oacute;nica HY TME (adsorci&oacute;n de PrP(Sc)) a los minerales del suelo en soluciones acuosas de tamp&oacute;n fosfato salino (PBS), cloruro de sodio, cloruro de calcio y agua desionizada mediante western blot. Tambi&eacute;n se evalu&oacute; la eficacia de la replicaci&oacute;n de priones consolidados despu&eacute;s de adsorci&oacute;n en estas soluciones por prote&iacute;na mal plegamiento de amplificaci&oacute;n c&iacute;clica (EPCP). Estudios de envejecimiento investig&oacute; la eficacia de desorci&oacute;n y replicaci&oacute;n de PrP (SC) hasta un a&ntilde;o despu&eacute;s de la adsorci&oacute;n en PBS o DI agua. Los resultados indican que qu&iacute;mica de soluci&oacute;n de adsorci&oacute;n puede afectar la capacidad de replicaci&oacute;n o desorci&oacute;n posterior del pri&oacute;n, especialmente despu&eacute;s de per&iacute;odos de incubaci&oacute;n de 30 d&iacute;as o m&aacute;s. Efectos observados fueron menores en el corto plazo (7 d o menos). Resultados de experimentos de envejecimiento a largo plazo demuestran que los priones no consolidados o priones atados a una amplia gama de superficies de suelo pueden replicar f&aacute;cilmente despu&eacute;s de un a&ntilde;o. Nuestros resultados sugieren que mientras que las interacciones del pri&oacute;n del suelo pueden variar con la qu&iacute;mica de la soluci&oacute;n, priones atados al suelo podr&iacute;an seguir siendo un riesgo para la transmisi&oacute;n de enfermedades por pri&oacute;n despu&eacute;s de meses en el medio ambiente.

Efectos de tiempo de soluci&oacute;n qu&iacute;mica y envejecimiento en la adsorci&oacute;n de la prote&iacute;na del pri&oacute;n y replicaci&oacute;n de priones suelo enlazado.

Prions enter the environment from infected hosts, bind to a wide range of soil and soil minerals, and remain highly infectious. Environmental sources of prions almost certainly contribute to the transmission of chronic wasting disease in cervids and scrapie in sheep and goats. While much is known about the introduction of prions into the environment and their interaction with soil, relatively little is known about prion degradation and inactivation by natural environmental processes. In this study, we examined the effect of repeated cycles of drying and wetting on prion fitness and determined that 10 cycles of repeated drying and wetting could reduce PrP(Sc) abundance, PMCA amplification efficiency and extend the incubation period of disease. Importantly, prions bound to soil were more susceptible to inactivation by repeated cycles of drying and wetting compared to unbound prions, a result which may be due to conformational changes in soil-bound PrP(Sc) or consolidation of the bonding between PrP(Sc) and soil. This novel finding demonstrates that naturally-occurring environmental process can degrade prions.

Mitigation of prion infectivity and conversion capacity by a simulated natural process--repeated cycles of drying and wetting.

Chronic wasting disease (CWD) is an emerging prion disease in North America. Recent identification of CWD in wild cervids from Norway raises the concern of the spread of CWD in Europe. CWD infectivity can enter the environment through live animal excreta and carcasses where it can bind to soil. Well-characterized hamster prion strains and CWD field isolates in unadsorbed or soil-adsorbed forms that were either hydrated or dehydrated were subjected to repeated rounds of freezing and thawing. We found that 500 cycles of repeated freezing and thawing of hydrated samples significantly decreased the abundance of PrP and reduced protein misfolding cyclic amplification (PMCA) seeding activity that could be rescued by binding to soil. Importantly, dehydration prior to freezing and thawing treatment largely protected PrP from degradation, and the samples maintained PMCA seeding activity. We hypothesize that redistribution of water molecules during the freezing and thawing process alters the stability of PrP aggregates. Overall, these results have significant implications for the assessment of prion persistence in the environment. Prions excreted into the environment by infected animals, such as elk and deer infected with chronic wasting disease, persist for years and thus facilitate horizontal transmission of the disease. Understanding the fate of prions in the environment is essential to control prion disease transmission. The significance of our study is that it provides information on the possibility of prion degradation and inactivation under natural weathering processes. This information is significant for remediation of prion-contaminated environments and development of prion disease control strategies.

Dehydration of Prions on Environmentally Relevant Surfaces Protects Them from Inactivation by Freezing and Thawing.

Prions can persist in the environment for extended periods of time after adsorption to surfaces, including soils, feeding troughs, or fences. Prion strain- and soil-specific differences in prion adsorption, infectivity, and response to inactivation may be involved in strain maintenance or emergence of new strains in a population. Extensive proteinase K (PK) digestion of Hyper (HY) and Drowsy (DY) PrP resulted in a greater reduction in the level of DY PrP than of HY PrP Use of the PK-digested material in protein misfolding cyclic amplification strain interference (PMCAsi) resulted in earlier emergence of HY PrP than of undigested controls. This result established that strain-specific alteration of the starting ratios of conversion-competent HY and DY PrP can alter strain emergence. We next investigated whether environmentally relevant factors such as surface binding and weathering could alter strain emergence. Adsorption of HY and DY PrP to silty clay loam (SCL), both separately and combined, resulted in DY interfering with the emergence of HY in PMCAsi in a manner similar to that seen with unbound controls. Similarly, repeated cycles of wetting and drying of SCL-bound HY and DY PrP did not alter the emergence of HY PrP compared to untreated controls. Importantly, these data indicate that prion strain interference can occur when prions are bound to surfaces. Interestingly, we found that drying of adsorbed brain homogenate on SCL could restore its ability to interfere with the emergence of HY, suggesting a novel strain interference mechanism. Overall, these data provide evidence that the emergence of a strain from a mixture can be influenced by nonhost factors. The prion strain, surface type, and matrix containing PrP can influence PrP surface adsorption. The cumulative effect of these factors can result in strain- and soil-specific differences in prion bioavailability. Environmental weathering processes can result in decreases in PrP conversion efficiency and infectivity. Little is known about how incomplete inactivation of surface-bound PrP affects transmission and prion strain emergence. Here, we show that strain interference occurs with soil-bound prions and that altering the ratios of prion strains by strain-specific inactivation can affect strain emergence. Additionally, we identify a novel mechanism of inhibition of prion conversion by environmental treatment-induced changes at the soil-protein interface altering strain emergence. These novel findings suggest that environmental factors can influence strain emergence of surface-bound prions.

Alteration of Prion Strain Emergence by Nonhost Factors.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic and persistent organic pollutant found in soils and sediments. It has been linked to several adverse health outcomes in humans and wildlife, including suppression of the immune system. TCDD is strongly sorbed to soils/sediments due to its extremely low water solubility. Presently, the bioavailability of soil/sediment-sorbed TCDD to mammals is not completely understood. Our previous studies demonstrated that TCDD adsorbed to representative inorganic geosorbents (i.e. porous silica and smectite clay) exhibited the same bioavailability to mice as TCDD dissolved in corn oil, whereas sequestration by activated carbons eliminated TCDD bioavailability. In this study, we evaluated the effects of amorphous natural organic matter (NOM), primarily in the form of aquatic humic and fulvic acids, on the mouse bioavailability of TCDD. An aqueous suspension of TCDD mixed with NOM was administered to mice via oral gavage. The relative bioavailability of TCDD was assessed by two sensitive aryl hydrocarbon receptor-mediated responses in mice: 1) hepatic induction of cyp1A1 mRNA; and 2) suppression of immunoglobulin M (IgM) antibody-forming cell (AFC) response which is an indicator of immunotoxicity. Hepatic induction of cyp1A1 mRNA and suppression of IgM AFC induced by TCDD were similar in the NOM-sorbed form and dissolved in corn oil, revealing no loss of bioavailability when associated with NOM. Hence, NOM-associated TCDD is as capable of suppressing humoral immunity in mice as TCDD dissolved in corn oil, indicating that NOM-sorbed TCDD is likely to fully retain its bioavailability to mammals and, by inference, humans.

Natural organic matter does not diminish the mammalian bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Chronic wasting disease (CWD) has been identified in 30 states in the United States, four provinces in Canada, and recently emerged in Scandinavia. The association of CWD prions with environmental materials such as soil, plants, and surfaces may enhance the persistence of CWD prion infectivity in the environment exacerbating disease transmission. Identifying and quantifying CWD prions in the environment is significant for prion monitoring and disease transmission control. A systematic method for CWD prion quantification from associated environmental materials, however, does not exist. In this study, we developed an innovative method for extracting prions from swabs and recovering CWD prions swabbed from different types of surfaces including glass, stainless steel, and wood. We found that samples dried on swabs were unfavorable for prion extraction, with the greatest prion recovery from wet swabs. Using this swabbing technique, the recovery of CWD prions dried to glass or stainless steel was approximately 30% in most cases, whereas that from wood was undetectable by conventional prion immunodetection techniques. Real-time quake-induced conversion (RT-QuIC) analysis of these same samples resulted in an increase of the detection limit of CWD prions from stainless steel by 4 orders of magnitude. More importantly, the RT-QuIC detection of CWD prions recovered from stainless steel surfaces using this method was similar to the original CWD prion load applied to the surface. This combined surface swabbing and RT-QuIC detection method provides an ultrasensitive means for prion detection across many settings and applications.

Sensitive detection of chronic wasting disease prions recovered from environmentally relevant surfaces.

Prion diseases are untreatable fatal transmissible neurodegenerative diseases that affect a wide range of mammals, including humans, and are caused by PrP, the infectious self-templating conformation of the host-encoded protein, PrP. Prion diseases can be transmitted via surfaces (e.g., forceps, EEG electrodes) in laboratory and clinical settings. Here, we use a combination of surface swabbing and real-time quaking-induced conversion (RT-QuIC) to test for residual surface-associated prions following prion disinfection. We found that treatment of several prion-contaminated laboratory and clinically relevant surfaces with either water or 70% EtOH resulted in robust detection of surface-associated prions. In contrast, treatment of surfaces with sodium hypochlorite resulted in a failure to detect surface-associated prions. RT-QuIC analysis of prion-contaminated stainless steel wires paralleled the findings of the surface swab studies. Importantly, animal bioassay and RT-QuIC analysis of the same swab extracts are in agreement. We report on conditions that may interfere with the assay that need to be taken into consideration before using this technique. Overall, this method can be used to survey laboratory and clinical surfaces for prion infectivity following prion decontamination protocols.IMPORTANCEPrion diseases can be accidentally transmitted in clinical and occupational settings. While effective means of prion decontamination exist, methods for determining the effectiveness are only beginning to be described. Here, we analyze surface swab extracts using real-time quaking-induced conversion (RT-QuIC) to test for residual prions following prion disinfection of relevant clinical and laboratory surfaces. We found that this method can rapidly determine the efficacy of surface prion decontamination. Importantly, examination of surface extracts with RT-QuIC and animal bioassay produced similar findings, suggesting that this method can accurately assess the reduction in prion titer. We identified surface contaminants that interfere with the assay, which may be found in clinical and laboratory settings. Overall, this method can enhance clinical and laboratory prion safety measures.

Qi Yuan

Division of Biomedical Sciences

Faculty of Medicine, Memorial University

A Lateralized Odor Learning Model in Neonatal Rats for Dissecting Neural Circuitry Underpinning Memory Formation

Prion Safety Laboratory Swipe Test

Qi Yuan

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Division of Biomedical Sciences

Faculty of Medicine, Memorial University

A Lateralized Odor Learning Model in Neonatal Rats for Dissecting Neural Circuitry Underpinning Memory Formation

Prion Safety Laboratory Swipe Test

Division of Biomedical Sciences