high-resolution-phonon-assisted-quasi-resonance-fluorescence

High Resolution Phonon-assisted Quasi-resonance Fluorescence Spectroscopy

High resolution optical spectroscopy methods are demanding in terms of either technology, equipment, complexity, time or a combination of these. Here we ...

UNIVERSITY OF CALIFORNIA, MERCED

Cyclotides &#x662F;&#x81EA;&#x7136;&#x53D1;&#x751F;&#x7684;&#x6700;&#x5927;&#x5BB6;&#x65CF;&#x5706;&#x5F62;&#x86CB;&#x767D;&#x3002;&#x5176;&#x4E2D;&#x8FD9;&#x4E9B;&#x57FA;&#x56E0;&#x7F16;&#x7801;&#x7684;&#x86CB;&#x767D;&#x8D28;&#x7684;&#x603B;&#x7AD9;&#x76F8;&#x8FDE;&#x65E0;&#x7F1D;&#x5730;&#x4E0E;&#x80BD;&#x952E;&#x5F62;&#x6210;&#x73AF;&#x5F62;&#x9AA8;&#x5E72;&#x7684;&#x673A;&#x5236;&#x662F;&#x672A;&#x77E5;&#x7684;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x62A5;&#x544A; cyclotide &#x7F16;&#x7801; cDNA &#x5E8F;&#x5217;&#x4ECE;&#x4E2D;&#x63D0;&#x7434;&#x8349;&#x690D;&#x7269;&#x5E76;&#x6BD4;&#x8F83;&#x5B83;&#x4EEC;&#x4E0E;&#x90A3;&#x4E9B;&#x4ECE;&#x4ECE;&#x8FDB;&#x5316;&#x7684;&#x89D2;&#x5EA6;&#x4E0D;&#x540C;&#x7684;&#x7269;&#x79CD;&#xFF0C;&#x767D;&#x82B1;&#x86C7;&#x7AF9;&#x3002;&#x6B64;&#x9176;&#x5BB6;&#x65CF;&#x7684;&#x4E2A;&#x522B;&#x6210;&#x5458;&#x5BF9;&#x4E00;&#x81F3;&#x4E09;&#x4E2A;&#x6210;&#x719F;&#x7684; cyclotide &#x57DF;&#x8FDB;&#x884C;&#x7F16;&#x7801;&#x3002;&#x8FD9;&#x4E9B;&#x57DF;&#x524D;&#x9762;&#x52A0; N &#x7EC8;&#x7AEF;&#x91CD;&#x590D;&#x533A;&#x57DF; &#xFF08;NTRs&#xFF09;&#xFF0C;&#x5747;&#x53D7;&#x5230;&#x4FDD;&#x80B2;&#x690D;&#x7269;&#x7269;&#x79CD;&#x5185;&#x4F46;&#x4E0D;&#x662F;&#x7269;&#x79CD;&#x4E4B;&#x95F4;&#x3002;&#x6211;&#x4EEC;&#x6709;&#x7ED3;&#x6784;&#x4E0A;&#x7684;&#x7279;&#x70B9;&#x5BF9;&#x5E94;&#x4E8E;&#x8FD9;&#x4E9B; NTRs &#x7684;&#x591A;&#x80BD;&#x548C;&#x663E;&#x793A;&#xFF0C;&#x5C3D;&#x7BA1;&#x4ED6;&#x4EEC;&#x6709;&#x6CA1;&#x6709;&#x5E8F;&#x5217;&#x540C;&#x6E90;&#x6027;&#xFF0C;&#x5B83;&#x4EEC;&#x5F62;&#x6210;&#x7ED3;&#x6784;&#x4E0A;&#x4FDD;&#x5B88;&#x7684;&#x963F;&#x5C14;&#x6CD5;&#x87BA;&#x65CB;&#x56FE;&#x6848;&#x3002;&#x6B64;&#x7ED3;&#x6784;&#x7684;&#x4FDD;&#x5B88;&#x6027;&#x8868;&#x660E;&#x4E3A;&#x4F53;&#x5185;&#x6298;&#x53E0;&#x3001; &#x52A0;&#x5DE5;&#xFF0C;&#x6216;&#x89E3;&#x6BD2;&#x7684;&#x524D;&#x4F53;&#x86CB;&#x767D;&#x4ECE; cyclotide &#x57DF;&#x4E2D;&#x5EF6;&#x7EED;&#x7740;&#x81F3;&#x5173;&#x91CD;&#x8981;&#x7684;&#x4F5C;&#x7528;&#x3002;

&#x53D7;&#x7275;&#x8FDE;&#x7684;&#x57FA;&#x56E0;&#x7F16;&#x7801;&#x7684;&#x86CB;&#x767D;&#x8D28;&#x5FAA;&#x73AF;&#x52A0;&#x5DE5;&#x4E2D;&#x5B88;&#x6052;&#x7684;&#x7ED3;&#x6784;&#x548C;&#x5E8F;&#x5217;&#x5143;&#x7D20;&#x3002;

The cyclotides are the largest family of naturally occurring circular proteins. The mechanism by which the termini of these gene-encoded proteins are linked seamlessly with a peptide bond to form a circular backbone is unknown. Here we report cyclotide-encoding cDNA sequences from the plant Viola odorata and compare them with those from an evolutionarily distinct species, Oldenlandia affinis. Individual members of this multigene family encode one to three mature cyclotide domains. These domains are preceded by N-terminal repeat regions (NTRs) that are conserved within a plant species but not between species. We have structurally characterized peptides corresponding to these NTRs and show that, despite them having no sequence homology, they form a structurally conserved alpha-helical motif. This structural conservation suggests a vital role for the NTR in the in vivo folding, processing, or detoxification of cyclotide domains from the precursor protein.

Conserved structural and sequence elements implicated in the processing of gene-encoded circular proteins.

Les cyclotides sont de la plus grande famille d&#39;origine naturelle prot&eacute;ines circulaires. On ne conna&icirc;t pas le m&eacute;canisme par lequel les terminus de ces prot&eacute;ines cod&eacute;es de g&egrave;ne sont li&eacute;s en toute transparence avec une liaison peptidique &agrave; constituer une base circulaire. Nous pr&eacute;sentons des ADNc codant pour cyclotide s&eacute;quences de l&#39;usine de Viola odorata et de les comparer avec ceux d&#39;une esp&egrave;ce &eacute;volutionnaires distincte, Oldenlandia affinis. Les membres individuels de cette famille multig&eacute;nique encodent un &agrave; trois domaines de cyclotide matures. Ces domaines sont pr&eacute;c&eacute;d&eacute;s par des r&eacute;gions de r&eacute;p&eacute;tition N-terminal (Representatives) qui sont conserv&eacute;es dans une esp&egrave;ce de plante, mais pas entre les esp&egrave;ces. On a caract&eacute;ris&eacute; la structure des peptides correspondant &agrave; ces stages et montrent que, malgr&eacute; leur n&#39;avoir aucune homologie de s&eacute;quence, ils forment un motif alpha-h&eacute;lico&iuml;dal structurellement conserv&eacute;. Cette conservation structurale sugg&egrave;re un r&ocirc;le vital pour le NTR in vivo pliant, traitement, ou d&eacute;toxication des domaines de cyclotide de la prot&eacute;ine pr&eacute;curseur.

Structurels et s&eacute;quence &eacute;l&eacute;ments conserv&eacute;s impliqu&eacute;s dans la transformation des prot&eacute;ines circulaires g&egrave;ne cod&eacute;.

Konservierte strukturelle und Sequenzelemente in der Verarbeitung von Gen codierten kreisf&#xF6;rmigen Proteine &#x200B;&#x200B;beteiligt ist.

I cyclotides sono la pi&ugrave; grande famiglia di biofiltri proteine circolare. Il meccanismo mediante il quale i termini di queste proteine codificate dal gene sono collegata senza soluzione di continuit&agrave; con un legame peptidico a formare una dorsale circolare &egrave; sconosciuto. Qui riportiamo la codifica cyclotide cDNA sequenze dalla pianta Viola odorata e confrontarli con quelli provenienti da una specie evolutionarily distinct, Oldenlandia affinis. Singoli membri di questa famiglia di multigene codificano uno a tre domini cyclotide maturo. Questi domini sono preceduti da regioni di ripetizione N-terminale (NTRs) che sono conservate all&#39;interno di una specie di pianta, ma non tra le specie. Ci hanno caratterizzato strutturalmente peptidi corrispondenti a questi NTRs e mostrare che, nonostante la loro non avendo alcuna omologia di sequenza, formano un motivo alfa-elicoidale strutturalmente conservato. Questa conservazione strutturale suggerisce un ruolo vitale per il NTR in vivo pieghevole, elaborazione, o detossificazione del cyclotide domini dalla proteina precursore.

Conservato elementi strutturali e di sequenza implicati nella trasformazione delle proteine circolare codificato dal gene.

Cyclotides &#x306A;&#x5929;&#x7136;&#x306E;&#x5BB6;&#x65CF;&#x304C;&#x6700;&#x5927;&#x3067;&#x3059;&#x5186;&#x5F62;&#x86CB;&#x767D;&#x8CEA;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x306B;&#x30B3;&#x30FC;&#x30C9;&#x3055;&#x308C;&#x308B;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306E;&#x30C6;&#x30EB;&#x30DF;&#x30CB;&#x5186;&#x5F62;&#x306E;&#x30D0;&#x30C3;&#x30AF;&#x30DC;&#x30FC;&#x30F3;&#x3092;&#x5F62;&#x6210;&#x3059;&#x308B;&#x30DA;&#x30D7;&#x30C1;&#x30C9;&#x7D50;&#x5408;&#x3068;&#x30B7;&#x30FC;&#x30E0;&#x30EC;&#x30B9;&#x306B;&#x30EA;&#x30F3;&#x30AF;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x304C;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F; cyclotide &#x306E; cDNA &#x3092;&#x5831;&#x544A;&#x30CB;&#x30AA;&#x30A4;&#x30B9;&#x30DF;&#x30EC;&#x5DE5;&#x5834;&#x304B;&#x3089;&#x306E;&#x30B7;&#x30FC;&#x30B1;&#x30F3;&#x30B9;&#x3068;&#x305D;&#x308C;&#x3089;&#x304C;&#x9032;&#x5316;&#x7684;&#x306B;&#x660E;&#x77AD;&#x306A;&#x7A2E;&#x3001;&#x767D;&#x82B1;&#x86C7;&#x820C;&#x8349;&#x30A2;&#x30D5;&#x30A3;&#x30CB;&#x30B9;&#x304B;&#x3089;&#x306E;&#x305D;&#x308C;&#x3089;&#x3092;&#x6BD4;&#x8F03;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x591A;&#x91CD;&#x907A;&#x4F1D;&#x5B50;&#x65CF;&#x306E;&#x500B;&#x3005; &#x306E;&#x30E1;&#x30F3;&#x30D0;&#x30FC;&#x306F;&#x3001;1 &#xFF5E; 3 &#x306E;&#x6210;&#x719F;&#x3057;&#x305F; cyclotide &#x30C9;&#x30E1;&#x30A4;&#x30F3;&#x3092;&#x30A8;&#x30F3;&#x30B3;&#x30FC;&#x30C9;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C9;&#x30E1;&#x30A4;&#x30F3;&#x304C;&#x690D;&#x7269;&#x7A2E;&#x5185;&#x3001;&#x7A2E;&#x9593;&#x3067;&#x306F;&#x306A;&#x304F;&#x4FDD;&#x5B58;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B; N &#x672B;&#x7AEF;&#x30EA;&#x30D4;&#x30FC;&#x30C8;&#x9818;&#x57DF; (NTRs) &#x304C;&#x5148;&#x884C;&#x3057;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306F;&#x3001;&#x3053;&#x308C;&#x3089;&#x306E; NTRs &#x306B;&#x5BFE;&#x5FDC;&#x3059;&#x308B;&#x30DA;&#x30D7;&#x30C1;&#x30C9;&#x69CB;&#x9020;&#x7684;&#x306B;&#x7279;&#x5FB4;&#x304C;&#x3042;&#x308B;&#x3057;&#x3001;&#x305D;&#x308C;&#x3089;&#x306E;&#x76F8;&#x540C;&#x6027;&#x3092;&#x6709;&#x3059;&#x308B;&#x306B;&#x3082;&#x304B;&#x304B;&#x308F;&#x3089;&#x305A;&#x3001;&#x5F7C;&#x3089;&#x306F;&#x69CB;&#x9020;&#x7684;&#x306B;&#x4FDD;&#x5B58;&#x3055;&#x308C;&#x305F;&#x30A2;&#x30EB;&#x30D5;&#x30A1; &#x30D8;&#x30EA;&#x30AB;&#x30EB; &#x30E2;&#x30C1;&#x30FC;&#x30D5;&#x5F62;&#x6210;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x306E;&#x69CB;&#x9020;&#x306E;&#x4FDD;&#x5168; NTR&#x3001;in vivo &#x3067;&#x306E;&#x6298;&#x308A;&#x7573;&#x307F;&#x3001;&#x51E6;&#x7406;&#x3001;&#x307E;&#x305F;&#x306F; cyclotide &#x30C9;&#x30E1;&#x30A4;&#x30F3;&#x306E;&#x524D;&#x99C6;&#x7269;&#x8CEA;&#x86CB;&#x767D;&#x8CEA;&#x304B;&#x3089;&#x306E;&#x89E3;&#x6BD2;&#x306E;&#x305F;&#x3081;&#x306B;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3092;&#x793A;&#x5506;&#x3057;&#x307E;&#x3059;&#x3002;

&#x5186;&#x5F62;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x907A;&#x4F1D;&#x5B50;&#x30A8;&#x30F3;&#x30B3;&#x30FC;&#x30C9;&#x306E;&#x51E6;&#x7406;&#x306B;&#x95A2;&#x4E0E;&#x3059;&#x308B;&#x4FDD;&#x5B58;&#x3055;&#x308C;&#x305F;&#x69CB;&#x9020;&#x3068;&#x30B7;&#x30FC;&#x30B1;&#x30F3;&#x30B9;&#x8981;&#x7D20;&#x3002;

Cyclotides&#xB294; &#xC790;&#xC5F0;&#xC2A4;&#xB7FD; &#xAC8C; &#xBC1C;&#xC0DD;&#xC758; &#xAC00;&#xC7A5; &#xD070; &#xAC00;&#xC871; &#xC6D0;&#xD615; &#xB2E8;&#xBC31;&#xC9C8;. &#xC774;&#xB7EC;&#xD55C; &#xC720;&#xC804;&#xC790; &#xC778;&#xCF54;&#xB529; &#xB2E8;&#xBC31;&#xC9C8; &#xD14C;&#xB974;&#xBBF8;&#xB2C8;&#xC640; &#xC5F0;&#xACB0; &#xB418;&#xC5B4; &#xC6D0;&#xD65C; &#xD558; &#xAC8C; &#xC21C;&#xD658; &#xBC31;&#xBCF8;&#xC744; &#xD615;&#xC131; &#xD558; &#xD3A9; &#xD2F0; &#xB4DC; &#xACB0;&#xD569; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC744; &#xC54C; &#xC218; &#xC788;&#xB2E4;. Cyclotide &#xC778;&#xCF54;&#xB529; Cdna&#xB97C; &#xBCF4;&#xACE0; &#xC6B0;&#xB9AC;&#xB294; &#xC5EC;&#xAE30; &#xBE44;&#xC62C;&#xB77C; odorata &#xACF5;&#xC7A5;&#xC5D0;&#xC11C; &#xC2DC;&#xD000;&#xC2A4;&#xB294; &#xC9C4;&#xD654; &#xC801;&#xC73C;&#xB85C; &#xB69C;&#xB837;&#xD55C; &#xC885; Oldenlandia affinis&#xC5D0;&#xC11C; &#xADF8;&#xB4E4;&#xC744; &#xBE44;&#xAD50;. &#xC774; multigene &#xAC00;&#xC871;&#xC758; &#xAC1C;&#xBCC4; &#xD68C;&#xC6D0; 1 ~ 3 &#xC131;&#xC219; cyclotide &#xB3C4;&#xBA54;&#xC778; &#xC778;&#xCF54;&#xB529;. &#xC774;&#xB7EC;&#xD55C; &#xB3C4;&#xBA54;&#xC778; &#xC55E;&#xC5D0; &#xC885;&#xC758; &#xC2DD;&#xBB3C; &#xB0B4;&#xC5D0;&#xC11C; &#xC885; &#xC0AC;&#xC774; &#xBCF4;&#xC874; &#xB418;&#xB294; N &#xB2E8;&#xC790; &#xBC18;&#xBCF5; &#xC601;&#xC5ED; (NTRs). &#xC6B0;&#xB9AC;&#xC640; &#xD3A9; &#xD2F0; &#xB4DC;&#xC5D0; &#xD574;&#xB2F9; &#xC774;&#xB7EC;&#xD55C; NTRs &#xD558; &#xD2B9;&#xC9D5; &#xAD6C;&#xC870;&#xC801;&#xC73C;&#xB85C; &#xADF8;&#xB4E4; &#xC2DC;&#xD000;&#xC2A4; homology &#xC544;&#xBB34; &#xB370;&#xC5D0; &#xBD88;&#xAD6C; &#xD558; &#xACE0;, &#xADF8;&#xB4E4;&#xC740; &#xAD6C;&#xC870;&#xC801;&#xC73C;&#xB85C; &#xBCF4;&#xC874;&#xB41C; &#xC54C;&#xD30C; &#xB098;&#xC120;&#xD615; &#xBAA8;&#xD2F0;&#xBE0C; &#xC591;&#xC2DD; &#xD45C;&#xC2DC;. &#xC774; &#xAD6C;&#xC870; &#xBCF4;&#xC874; vivo&#xC5D0;&#xC11C; &#xC811;&#xAE30;, &#xCC98;&#xB9AC;, &#xB610;&#xB294; &#xC804;&#xC870; &#xB2E8;&#xBC31;&#xC9C8;&#xC5D0;&#xC11C; cyclotide &#xB3C4;&#xBA54;&#xC778;&#xC758; &#xD574;&#xB3C5; NTR&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xC81C;&#xC548; &#xD569;&#xB2C8;&#xB2E4;.

&#xBCF4;&#xC874;&#xB41C; &#xBC0F; &#xC2DC;&#xD000;&#xC2A4; &#xAD6C;&#xC870; &#xC694;&#xC18C; &#xC21C;&#xD658; &#xB2E8;&#xBC31;&#xC9C8; &#xC720;&#xC804;&#xC790; &#xC778;&#xCF54;&#xB529; &#xCC98;&#xB9AC;&#xC5D0; &#xC5F0;&#xB8E8;.

Los cyclotides son la familia m&aacute;s grande de natural circulares prote&iacute;nas. Se desconoce el mecanismo por el cual los t&eacute;rminos de estas prote&iacute;nas codificadas por el gen se ligan perfectamente con un enlace pept&iacute;dico para formar una estructura circular. Aqu&iacute; divulgamos cDNA cyclotide-codificaci&oacute;n secuencias de la planta Viola odorata y compararlos con los de una especie evolutivamente distinta, Oldenlandia affinis. Los miembros de esta familia de multigenes codifican maduro cyclotide de uno a tres dominios. Estos dominios son precedidos por regiones de repetici&oacute;n de N-terminal (S.r.n.t.) que se conservan dentro de una especie de planta, pero no entre especies. Nos han caracterizado estructuralmente p&eacute;ptidos que corresponden a estos S.r.n.t. y mostrar que, a pesar de no tener ninguna homolog&iacute;a de secuencia, forman un motivo estructural conservado de alfa-helicoidal. Esta conservaci&oacute;n estructural sugiere un papel vital para el NTR en in vivo plegable, procesamiento, o desintoxicaci&oacute;n de cyclotide los dominios de la prote&iacute;na precursora.

Conservado los elementos estructurales y secuencia implicados en el procesamiento de prote&iacute;nas circulares codificada por el gen.

A large number of macrocyclic miniproteins with diverse biological activities have been isolated from the Rubiaceae, Violaceae, and Cucurbitaceae plant families in recent years. Here we report the three-dimensional structure determined using (1)H NMR spectroscopy and demonstrate potent insecticidal activity for one of these peptides, kalata B2. This peptide is one of the major components of an extract from the leaves of the plant Oldenlandia affinis. The structure consists of a distorted triple-stranded beta-sheet and a cystine knot arrangement of the disulfide bonds and is similar to those described for other members of the cyclotide family. The unique cyclic and knotted nature of these molecules makes them a fascinating example of topologically complex proteins. Examination of the sequences reveals that they can be separated into two subfamilies, one of which contains a larger number of positively charged residues and has a bracelet-like circularization of the backbone. The second subfamily contains a backbone twist due to a cis-peptidyl-proline bond and may conceptually be regarded as a molecular Mobius strip. Kalata B2 is the second putative member of the Mobius cyclotide family to be structurally characterized and has a cis-peptidyl-proline bond, thus validating the suggested name for this subfamily of cyclotides. The observation that kalata B2 inhibits the growth and development of Helicoverpa armigera larvae suggests a role for the cyclotides in plant defense. A comparison of the sequences and structures of kalata B1 and B2 provides insight into the biological activity of these peptides.

Isolation, solution structure, and insecticidal activity of kalata B2, a circular protein with a twist: do Möbius strips exist in nature?

The human malaria parasite, Plasmodium falciparum, utilizes multiple ligand-receptor interactions for the invasion of human erythrocytes. Members of the reticulocyte binding protein homolog (PfRh) family have been shown to be critical for directing parasites to alternative erythrocyte receptors that define invasion pathways. Recent studies have identified gene amplification, sequence polymorphism, and variant expression of PfRh paralogs as mechanisms underlying discrimination between pathways for invasion. In this study, we find considerable heterogeneity in the invasion profiles of clonal, uncultured P. falciparum parasite isolates from a low-transmission area in Senegal. Molecular analyses revealed minimal variation in protein expression levels of the PfRh ligands, PfRh1, PfRh2a, and PfRh2b, and an absence of gene amplification in these isolates. However, significant sequence polymorphism was found within repeat regions of PfRh1, PfRh2a, and PfRh2b. Furthermore, we identified a large sequence deletion ( approximately 0.58 kb) in the C-terminal region of the PfRh2b gene at a high prevalence in this population. In contrast to findings of earlier studies, we found no associations between specific sequence variants and distinct invasion pathways. Overall these data highlight the importance of region-specific elaborations in PfRh sequence and expression polymorphisms, which has important implications in our understanding of how the malaria parasite responds to polymorphisms in erythrocyte receptors and/or evades the immune system.

Molecular analysis of erythrocyte invasion in Plasmodium falciparum isolates from Senegal.

Plant cyclotides are a large family of naturally occurring circular proteins that are produced from linear precursors containing one, two or three cyclotide domains. The mechanism of excision of the cyclotide domains and ligation of the free N- and C-termini to produce the circular peptides has not been elucidated. Here, we investigate production of the prototypic cyclotide kalata B1 from the precursor Oak1 from the African plant Oldenlandia affinis. Immunoprecipitation experiments and MALDI-TOF mass spectrometry analysis showed that O. affinis only produces mature kalata B1, whereas transgenic Arabidopsis thaliana, Nicotiana tabacum and Nicotiana benthamiana produced both linear and circular forms. Circular peptides were not produced when a highly conserved asparagine residue at the C-terminal processing site of the cyclotide domain was replaced with an alanine or an aspartate residue, or when the conserved C-terminal tripeptide motif was truncated. We propose that there are two processing pathways in planta: one to produce the mature cyclotide and the other to produce linear variants that ultimately cannot be cyclized.

Biosynthesis of circular proteins in plants.

Erythrocyte invasion by Plasmodium falciparum: multiple ligand-receptor interactions and phenotypic switching.

Apicomplexan parasites employ multiple adhesive ligands for recognition and entry into host cells. The Duffy binding-like (DBL) and the reticulocyte binding protein-like (RBL) families are central to the invasion of erythrocytes by the malaria parasite. These type-1 transmembrane proteins are composed of large ectodomains and small conserved cytoplasmic tail domains. The cytoplasmic tail domain of the micronemal DBL protein EBA-175 is required for a functional ligand-receptor interaction, but not for correct trafficking and localisation. Here we focus on the cytoplasmic tail domain of the rhoptry-localised Plasmodium falciparum RBL PfRh2b. We have identified a conserved sequence of six amino acids, enriched in acidic residues, in the cytoplasmic tail domains of RBL proteins from Plasmodium spp. Genetic analyses reveal that the entire cytoplasmic tail and the conserved motif within the cytoplasmic tail are indispensable for invasion P. falciparum. Site-directed mutagenesis of the conserved moiety reveals that changes in the order of the amino acids of the conserved moiety, but not the charge of the sequence, can be tolerated. Shuffling of the motif has no effect on either invasion phenotype or PfRh2b expression and trafficking. Although the PfRh2b gene can be readily disrupted, our results suggest that modification of the PfRh2b cytoplasmic tail results in strong dominant negative activity, highlighting important differences between the PfRh2b and EBA-175 invasion ligands.

Genetic analysis of the cytoplasmic domain of the PfRh2b merozoite invasion protein of Plasmodium falciparum.

&#x6076;&#x6027;&#x759F;&#x539F;&#x866B;&#x662F;&#x5176;&#x4E2D;&#x6700;&#x81F4;&#x547D;&#x7684;&#x759F;&#x539F;&#x866B;&#x7269;&#x79CD;&#x4F20;&#x67D3;&#x7ED9;&#x4EBA;&#x7C7B;&#x3002;&#x4E0D;&#x540C;&#x759F;&#x539F;&#x866B;&#x682A;&#x7684;&#x5165;&#x4FB5;&#x548C;&#x4ED6;&#x4EEC;&#x7684;&#x80FD;&#x529B;&#xFF0C;&#x4ED6;&#x4EEC;&#x5229;&#x7528;&#x4E0D;&#x540C;&#x7684;&#x53D7;&#x4F53;&#x66F2;&#x76EE;&#x4E2D;&#x5207;&#x6362;&#x4E3A;&#x7EA2;&#x7EC6;&#x80DE;&#x53D7;&#x4F53;&#x4F9D;&#x8D56;&#x5404;&#x4E0D;&#x76F8;&#x540C;&#x3002;&#x5165;&#x4FB5;&#x914D;&#x4F53;&#x7684;&#x7F51;&#x7EC7;&#x7EA2;&#x7EC6;&#x80DE;&#x7ED3;&#x5408;&#x86CB;&#x767D;&#x6837; (RBL) &#x5BB6;&#x5EAD;&#x6210;&#x5458;&#x90FD;&#x5047;&#x5B9A;&#x80FD;&#x591F;&#x53D1;&#x6325;&#x6838;&#x5FC3;&#x7684;&#x4F5C;&#x7528;&#xFF0C;&#x5728;&#x786E;&#x5B9A;&#x914D;&#x4F53;-&#x53D7;&#x4F53;&#x4E4B;&#x95F4;&#x7684;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#xFF0C;&#x79F0;&#x4E3A;&#x5165;&#x4FB5;&#x9014;&#x5F84;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x62A5;&#x544A; PfRh2b &#x548C; PfRh2a &#x7684; W2mef&#xFF0C;&#x662F;&#x4E25;&#x91CD;&#x4F9D;&#x8D56;&#x4E8E;&#x553E;&#x6DB2;&#x9178;&#x53D7;&#x4F53;&#x5165;&#x4FB5;&#xFF0C;&#x548C; PfRh2b &#x914D;&#x4F53;&#x662F;&#x529F;&#x80FD;&#x5728;&#x6B64;&#x5BC4;&#x751F;&#x866B;&#x80CC;&#x666F;&#x4E2D;&#x663E;&#x793A;&#x7684;&#x5BC4;&#x751F;&#x866B;&#x5E94;&#x53D8;&#x7684;&#x9776;&#x5411;&#x6027;&#x7684;&#x57FA;&#x56E0;&#x7684;&#x4E2D;&#x65AD;&#x3002;&#x50CF;&#x7236;&#x6BCD;&#x884C;&#xFF0C;&#x7F3A;&#x5C11; PfRh2a &#x6216; PfR2b &#x7684;&#x5BC4;&#x751F;&#x866B;&#x53EF;&#x4EE5;&#x5207;&#x6362;&#x5230;&#x72EC;&#x7ACB;&#x4E8E;&#x553E;&#x6DB2;&#x9178;&#x7684;&#x5165;&#x4FB5;&#x9014;&#x5F84;&#x3002;&#x4F46;&#x662F;&#xFF0C;&#x4E24;&#x4E2A;&#x5F00;&#x5173;&#x7684;&#x7EBF;&#x6761;&#x8868;&#x73B0;&#x51FA;&#x6548;&#x7387;&#x964D;&#x4F4E;&#x5165;&#x4FB5;&#x5230;&#x553E;&#x6DB2;&#x9178;&#x67AF;&#x7AED;&#x7684;&#x5355;&#x5143;&#x683C;&#xFF0C;&#x5728;&#x5165;&#x4FB5;&#x901A;&#x8FC7;&#x72EC;&#x7ACB;&#x4E8E;&#x553E;&#x6DB2;&#x9178;&#x53D7;&#x4F53; PfRh2b &#x548C; PfRh2a &#x6697;&#x793A;&#x4F5C;&#x7528;&#x3002;&#x6211;&#x4EEC;&#x8FD8;&#x627E;&#x5230;&#x4E00;&#x79CD;&#x9009;&#x62E9;&#x6027;&#x538B;&#x529B;&#x727A;&#x7272; PfRh2a PfRh2b &#x8868;&#x8FBE;&#x7684;&#x91CD;&#x7EC4;&#x3002;&#x6211;&#x4EEC;&#x7684;&#x7ED3;&#x679C;&#x7531;&#x759F;&#x539F;&#x866B;&#x7684;&#x5BC4;&#x751F;&#x866B;&#xFF0C;&#x63ED;&#x793A;&#x9057;&#x4F20;&#x80CC;&#x666F;&#x7684;&#x914D;&#x4F53;-&#x53D7;&#x4F53;&#x7528;&#x6CD5;&#x7684;&#x91CD;&#x8981;&#x6027;&#xFF0C;&#x5E76;&#x5EFA;&#x8BAE;&#x534F;&#x8C03;&#x8868;&#x8FBE;&#x7684; PfRh2a&#xFF0C;PfRh2b &#x4E00;&#x8D77;&#x8C03;&#x89E3;&#x6709;&#x6548;&#x72EC;&#x7ACB;&#x4E8E;&#x553E;&#x6DB2;&#x9178;&#x7684;&#x7EA2;&#x7EC6;&#x80DE;&#x5165;&#x4FB5;&#x3002;

&#x759F;&#x539F;&#x866B;&#x6076;&#x6027;&#x759F;&#x539F;&#x866B;&#x4FB5;&#x5165;&#x7EA2;&#x7EC6;&#x80DE;&#x80F6;&#x86CB;&#x767D;&#x4E4B;&#x95F4;&#x7684;&#x534F;&#x540C;&#x6027;&#x3002;

Plasmodium falciparum is the most virulent of the Plasmodium species infective to humans. Different P. falciparum strains vary in their dependence on erythrocyte receptors for invasion and their ability to switch in their utilization of different receptor repertoires. Members of the reticulocyte-binding protein-like (RBL) family of invasion ligands are postulated to play a central role in defining ligand-receptor interactions, known as invasion pathways. Here we report the targeted gene disruption of PfRh2b and PfRh2a in W2mef, a parasite strain that is heavily dependent on sialic-acid receptors for invasion, and show that the PfRh2b ligand is functional in this parasite background. Like the parental line, parasites lacking either PfRh2a or PfR2b can switch to a sialic acid-independent invasion pathway. However, both of the switched lines exhibit a reduced efficiency for invasion into sialic acid-depleted cells, suggesting a role for both PfRh2b and PfRh2a in invasion via sialic acid-independent receptors. We also find a strong selective pressure for the reconstitution of PfRh2b expression at the expense of PfRh2a. Our results reveal the importance of genetic background in ligand-receptor usage by P. falciparum parasites, and suggest that the co-ordinate expression of PfRh2a, PfRh2b together mediate efficient sialic acid-independent erythrocyte invasion.

Cooperativity between Plasmodium falciparum adhesive proteins for invasion into erythrocytes.

Plasmodium falciparum est le plus virulent de l&#39;esp&egrave;ce Plasmodium infectieux pour l&#39;homme. Souches diff&eacute;rentes de P. falciparum varient dans leur d&eacute;pendance sur les r&eacute;cepteurs &eacute;rythrocytaires invasion et leur capacit&eacute; &agrave; passer dans leur utilisation des r&eacute;pertoires de r&eacute;cepteurs diff&eacute;rents. Membres de la famille de (RBL) comme prot&eacute;ine r&eacute;ticulocytes-liaison des ligands de l&#39;invasion sont postul&eacute;s &agrave; jouer un r&ocirc;le central dans la d&eacute;finition des interactions ligand-r&eacute;cepteur, connues comme voies d&#39;invasion. Nous rapportons ici l&#39;interruption du g&egrave;ne cibl&eacute; de PfRh2b et de PfRh2a en W2mef, une souche du parasite qui est fortement tributaire de l&#39;acide sialique r&eacute;cepteurs pour l&#39;invasion et montrent que le ligand PfRh2b fonctionne en arri&egrave;re-plan de ce parasite. Comme la lign&eacute;e parentale, parasites, sans PfRh2a ni PfR2b peuvent basculer vers une voie ind&eacute;pendante de l&#39;acide sialique invasion. Toutefois, les deux lignes commut&eacute;es pr&eacute;sentent une efficacit&eacute; r&eacute;duite pour l&#39;invasion dans les cellules pauvre en acide sialique, sugg&eacute;rant un r&ocirc;le pour les PfRh2b et les PfRh2a dans invasion via des r&eacute;cepteurs de l&#39;acide sialique ind&eacute;pendant. On trouve aussi une forte pression s&eacute;lective pour la reconstitution de l&#39;expression de PfRh2b au d&eacute;triment de la PfRh2a. Nos r&eacute;sultats r&eacute;v&egrave;lent l&#39;importance du patrimoine g&eacute;n&eacute;tique dans l&#39;utilisation de ligand-r&eacute;cepteur par des parasites P. falciparum et sugg&egrave;rent que l&#39;expression de coordonner des PfRh2a, PfRh2b m&eacute;diateur ensemble invasion efficace ind&eacute;pendant de l&#39;acide sialique &eacute;rythrocytaire.

Coop&eacute;rativit&eacute; entre prot&eacute;ines adh&eacute;sives de Plasmodium falciparum &agrave; l&#39;invasion dans les &eacute;rythrocytes.

Plasmodium Falciparum ist die b&ouml;sartigste der Plasmodium-Arten f&uuml;r den Menschen infekti&ouml;s. Verschiedene p. Falciparum Belastungen variieren in ihrer Abh&auml;ngigkeit von Erythrozyten-Rezeptoren f&uuml;r die Invasion und ihre F&auml;higkeit, in ihrer Auslastung der unterschiedlichen Rezeptor-Repertoire zu wechseln. Reticulocyte-verbindliches Protein-wie (RBL) Familienmitglieder Einmarsch Liganden sind, spielen eine zentrale Rolle bei der Definition von Ligand-Rezeptor-Interaktionen, bekannt als Einmarsch Bahnen postuliert. Hier berichten wir die gezielte gen-Unterbrechung der PfRh2b und PfRh2a in W2mef, ein Parasit-Stamm, der ist stark abh&auml;ngig von sialic-S&auml;ure-Rezeptoren f&uuml;r die Invasion und geht hervor, dass die PfRh2b-Ligand funktional in diesem Parasit-Hintergrund. Wie die Elternlinie k&ouml;nnen Parasiten fehlt entweder PfRh2a oder PfR2b Sialins&auml;ure-unabh&auml;ngige Einmarsch Weg wechseln. Allerdings zeigen die beiden geschalteten Zeilen eine geringere Effizienz f&uuml;r das Eindringen in Sialins&auml;ure-abgereichertem Zellen, schl&auml;gt eine Rolle f&uuml;r PfRh2b und PfRh2a Invasion &uuml;ber Sialins&auml;ure-unabh&auml;ngige Rezeptoren. Wir finden auch einen starken selektiven Druck die Neubildung der PfRh2b Ausdruck auf Kosten der PfRh2a. Unsere Ergebnisse zeigen die Bedeutung der genetischen Hintergrund in Ligand-Rezeptor-Nutzung durch p. Falciparum Parasiten, und schlagen vor, da&szlig; koordinieren Ausdruck PfRh2a, PfRh2b gemeinsam effiziente Sialins&auml;ure-unabh&auml;ngige Erythrozyten Einmarsch vermitteln.

Kooperation zwischen Plasmodium Falciparum anhaftenden Proteinen f&uuml;r das Eindringen in Erythrozyten.

Plasmodium falciparum &egrave; il pi&ugrave; virulento delle specie di Plasmodium infettivi per l&#39;uomo. Ceppi di p. falciparum differenti variano in dipendenza dai loro recettori degli eritrociti per invasione e la loro capacit&agrave; di passare nel loro utilizzo di repertori diversi recettori. Membri della famiglia dei reticolociti-binding proteina-come (RBL) di ligandi di invasione sono postulati di giocare un ruolo centrale nella definizione delle interazioni ligando-recettore, note come vie di invasione. Qui riportiamo la rottura mirata del gene di PfRh2b e PfRh2a in W2mef, un ceppo di parassita che &egrave; fortemente dipendente da acido sialico recettori per l&#39;invasione e dimostrano che il ligando PfRh2b &egrave; funzionale a questo sfondo parassita. Come la linea parentale, parassiti carente o PfRh2a o PfR2b possono passare a un percorso indipendente dall&#39;acido sialico invasione. Tuttavia, entrambe le linee commutate presentano una ridotta efficienza per invasione in cellule acido sialico-esaurito, suggerendo un ruolo sia per PfRh2b e PfRh2a in invasione tramite i recettori acido sialico-indipendente. Troviamo anche una forte pressione selettiva per la ricostituzione dell&#39;espressione PfRh2b a scapito di PfRh2a. I nostri risultati suggeriscono che l&#39;espressione coordinata di PfRh2a, PfRh2b mediare insieme invasione efficiente acido sialico-indipendente degli eritrociti e rivelano l&#39;importanza del background genetico nell&#39;utilizzo di ligando-recettore da p. falciparum parassiti.

Cooperativit&agrave; tra proteine adesive di Plasmodium falciparum per invasione in eritrociti.

&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x539F;&#x866B;&#x306F;&#x3001;&#x6700;&#x3082;&#x75C5;&#x539F;&#x6027;&#x539F;&#x866B;&#x7A2E;&#x306E;&#x4EBA;&#x9593;&#x306B;&#x611F;&#x67D3;&#x6027;&#x306E;&#x3067;&#x3059;&#x3002;&#x7570;&#x306A;&#x308B; p. &#x71B1;&#x5E2F;&#x71B1;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x539F;&#x866B;&#x306E;&#x7CFB;&#x7D71;&#x4FB5;&#x7565;&#x3068;&#x7570;&#x306A;&#x3063;&#x305F;&#x53D7;&#x5BB9;&#x4F53;&#x30EC;&#x30D1;&#x30FC;&#x30C8;&#x30EA;&#x30FC;&#x306E;&#x6D3B;&#x7528;&#x3067;&#x5207;&#x308A;&#x66FF;&#x3048;&#x308B;&#x80FD;&#x529B;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x8D64;&#x8840;&#x7403;&#x53D7;&#x5BB9;&#x4F53;&#x3078;&#x306E;&#x4F9D;&#x5B58;&#x304C;&#x7570;&#x306A;&#x308A;&#x307E;&#x3059;&#x3002;&#x7DB2;&#x72B6;&#x7D50;&#x5408;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x69D8; (RBL) &#x5BB6;&#x65CF;&#x4FB5;&#x7565;&#x30EA;&#x30AC;&#x30F3;&#x30C9;&#x306E;&#x4FB5;&#x5165;&#x7D4C;&#x8DEF;&#x3068;&#x3057;&#x3066;&#x77E5;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x3001;ligand &#x53D7;&#x5BB9;&#x5668;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x3092;&#x5B9A;&#x7FA9;&#x3059;&#x308B;&#x4E2D;&#x5FC3;&#x7684;&#x306A;&#x5F79;&#x5272;&#x3092;&#x518D;&#x751F;&#x3059;&#x308B;&#x306B;&#x4EEE;&#x5B9A;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;PfRh2b &#x3068; PfRh2a &#x3067; W2mef&#x3001;&#x30B7;&#x30A2;&#x30EB;&#x9178;&#x53D7;&#x5BB9;&#x4F53;&#x306B;&#x4FB5;&#x653B;&#x3001;&#x305D;&#x3057;&#x3066;&#x30B7;&#x30E7;&#x30FC;&#x306E; PfRh2b &#x30EA;&#x30AC;&#x30F3;&#x30C9;&#x3053;&#x306E;&#x5BC4;&#x751F;&#x866B;&#x306E;&#x30D0;&#x30C3;&#x30AF; &#x30B0;&#x30E9;&#x30A6;&#x30F3;&#x30C9;&#x3067;&#x6A5F;&#x80FD;&#x3057;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x306B;&#x5927;&#x304D;&#x304F;&#x4F9D;&#x5B58;&#x3057;&#x3066;&#x3044;&#x308B;&#x5BC4;&#x751F;&#x866B;&#x3072;&#x305A;&#x307F;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x7834;&#x58CA;&#x3092;&#x5831;&#x544A;&#x3057;&#x307E;&#x3059;&#x3002;&#x89AA;&#x306E;&#x884C;&#x306E;&#x3088;&#x3046;&#x306A; PfRh2a &#x307E;&#x305F;&#x306F; PfR2b &#x306E;&#x3044;&#x305A;&#x308C;&#x304B;&#x3092;&#x6B20;&#x304F;&#x5BC4;&#x751F;&#x866B;&#x3078;&#x306E;&#x30B7;&#x30A2;&#x30EB;&#x9178;&#x975E;&#x4F9D;&#x5B58;&#x306E;&#x4FB5;&#x5165;&#x7D4C;&#x8DEF;&#x3092;&#x5207;&#x308A;&#x66FF;&#x3048;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x30B9;&#x30A4;&#x30C3;&#x30C1;&#x306E;&#x884C;&#x306E;&#x4E21;&#x65B9;&#x306E;&#x30B7;&#x30A2;&#x30EB;&#x9178;&#x67AF;&#x6E07;&#x7D30;&#x80DE;&#x3078;&#x306E;&#x4FB5;&#x5165;&#x306E; PfRh2b &#x3068; PfRh2a &#x306E;&#x4E21;&#x65B9;&#x306E;&#x5F79;&#x5272;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x30B7;&#x30A2;&#x30EB;&#x9178;&#x72EC;&#x7ACB;&#x53D7;&#x5BB9;&#x4F53;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x6D78;&#x6F64;&#x306E;&#x305F;&#x3081;&#x306E;&#x6E1B;&#x3089;&#x3055;&#x308C;&#x305F;&#x52B9;&#x7387;&#x3092;&#x5C55;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x3082; PfRh2b &#x5F0F; PfRh2a &#x3092;&#x72A0;&#x7272;&#x306B;&#x3057;&#x3066;&#x306E;&#x518D;&#x69CB;&#x6210;&#x306E;&#x305F;&#x3081;&#x306E;&#x5F37;&#x529B;&#x306A;&#x9078;&#x629E;&#x5727;&#x3092;&#x898B;&#x3064;&#x3051;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306E;&#x7D50;&#x679C;&#x306F;&#x3001;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x5BC4;&#x751F;&#x866B;&#x306B;&#x3088;&#x3063;&#x3066;&#x907A;&#x4F1D;&#x7684;&#x80CC;&#x666F;&#x306E; ligand &#x53D7;&#x5BB9;&#x5668;&#x4F7F;&#x7528;&#x91CF;&#x306E;&#x91CD;&#x8981;&#x6027;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x3001;&#x8ABF;&#x6574;&#x5F0F; PfRh2a&#x3001;PfRh2b &#x304C;&#x4E00;&#x7DD2;&#x306B;&#x52B9;&#x7387;&#x7684;&#x306A;&#x30B7;&#x30A2;&#x30EB;&#x9178;&#x72EC;&#x7ACB;&#x8D64;&#x8840;&#x7403;&#x4FB5;&#x5165;&#x3092;&#x4EF2;&#x4ECB;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x304A;&#x52E7;&#x3081;&#x3002;

&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x539F;&#x866B;&#x71B1;&#x5E2F;&#x71B1;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x539F;&#x866B;&#x306E;&#x63A5;&#x7740;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x8D64;&#x8840;&#x7403;&#x3078;&#x306E;&#x4FB5;&#x5165;&#x306E;&#x5354;&#x540C;&#x6027;&#x3002;

Plasmodium falciparum&#xC740; &#xC778; &#xAC04;&#xC5D0; &#xAC8C; &#xAC10;&#xC5FC; Plasmodium &#xC885;&#xC758; &#xAC00;&#xC7A5; &#xCE58;&#xBA85;&#xC801;&#xC778;. P. falciparum &#xB2E4;&#xB978; &#xBCC0;&#xC885; &#xC801;&#xD608;&#xAD6C; &#xCE68;&#xC785;&#xACFC; &#xB2E4;&#xB978; &#xC218;&#xC6A9; &#xCCB4; &#xBC94;&#xC720;&#xB7FD;&#xC758; &#xC0AC;&#xC6A9;&#xB960;&#xC5D0; &#xC804;&#xD658; &#xD558;&#xB294; &#xADF8;&#xB4E4;&#xC758; &#xAE30;&#xB2A5;&#xC5D0; &#xB300; &#xD55C; &#xC218;&#xC6A9; &#xCCB4;&#xC5D0; &#xB300; &#xD55C; &#xC885;&#xC18D;&#xC131;&#xC5D0; &#xB530;&#xB77C; &#xB2E4;&#xB985;&#xB2C8;&#xB2E4;. &#xCE68;&#xACF5; ligands&#xC758; reticulocyte &#xBC14;&#xC778;&#xB529; &#xB2E8;&#xBC31;&#xC9C8; &#xAC19;&#xC740; (RBL) &#xAC00;&#xC871;&#xC758; &#xAD6C;&#xC131;&#xC6D0;&#xC740; &#xB9AC;&#xAC04;&#xB4DC;-&#xC218;&#xC6A9; &#xCCB4; &#xC0C1;&#xD638; &#xC791;&#xC6A9;, &#xCE68;&#xC785; &#xACBD;&#xB85C; &#xB77C;&#xACE0; &#xC815;&#xC758;&#xC5D0; &#xC911;&#xC2EC; &#xC5ED;&#xD560;&#xC744; postulated. &#xC5EC;&#xAE30; &#xC6B0;&#xB9AC;&#xB294; PfRh2b &#xBC0F; PfRh2a W2mef, PfRh2b &#xB9AC;&#xAC04;&#xB4DC;&#xB294;&#xC774; &#xAE30;&#xC0DD;&#xCDA9; &#xBC31;&#xADF8;&#xB77C;&#xC6B4;&#xB4DC;&#xC5D0;&#xC11C; &#xC791;&#xB3D9; &#xD558;&#xB294; &#xACF5;&#xC5F0;&#xC5D0; &#xB300; &#xD55C; &#xCE68;&#xACF5;, sialic &#xC0B0; &#xC218;&#xC6A9; &#xCCB4;&#xC5D0; &#xB530;&#xB77C; &#xD06C;&#xAC8C; &#xB2EC;&#xB77C; &#xC9D1;&#xB2C8;&#xB2E4; &#xAE30;&#xC0DD;&#xCDA9; &#xC2A4;&#xD2B8;&#xB808;&#xC778;&#xC5D0;&#xC5D0;&#xC11C; &#xD0C0;&#xAC9F;&#xB41C; &#xC720;&#xC804;&#xC790; &#xC7A5;&#xC560; &#xBCF4;&#xACE0;&#xC11C;. &#xBD80;&#xBAA8;&#xC758; &#xC120; &#xCC98;&#xB7FC; &#xAE30;&#xC0DD;&#xCDA9; PfRh2a &#xB610;&#xB294; PfR2b &#xBD80;&#xC871; sialic &#xC0B0; &#xB3C5;&#xB9BD;&#xC801;&#xC778; &#xCE68;&#xC785; &#xACBD;&#xB85C; &#xC804;&#xD658;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;, &#xB450; &#xC2A4;&#xC704;&#xCE58; &#xB77C;&#xC778; sialic &#xC0B0; &#xB3C5;&#xB9BD;&#xC801;&#xC778; &#xC218;&#xC6A9; &#xCCB4;&#xB97C; &#xD1B5;&#xD574; &#xCE68;&#xB7B5;&#xC5D0; PfRh2b &#xBC0F; Pfrh2a&#xC5D0; &#xB300; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xC81C;&#xC548; sialic &#xC0B0; &#xACE0;&#xAC08; &#xC138;&#xD3EC;&#xB85C; &#xCE68;&#xC785;&#xC744; &#xC704;&#xD574; &#xAC10;&#xC18C; &#xD6A8;&#xC728;&#xC744; &#xC804;&#xC2DC;. &#xC6B0;&#xB9AC;&#xB294; &#xB610;&#xD55C; PfRh2a &#xB300;&#xC2E0; PfRh2b &#xC2DD;&#xC758; &#xC7AC;&#xAD6C;&#xC131;&#xC5D0; &#xB300; &#xD55C; &#xAC15;&#xB825;&#xD55C; &#xC120;&#xD0DD;&#xC801; &#xC555;&#xB825;&#xC744; &#xBC1C;&#xACAC;. &#xC6B0;&#xB9AC;&#xC758; &#xACB0;&#xACFC; P. falciparum &#xAE30;&#xC0DD;&#xCDA9;&#xC5D0; &#xC758;&#xD574; &#xB9AC;&#xAC04;&#xB4DC;-&#xC218;&#xC6A9; &#xCCB4; &#xC0AC;&#xC6A9;&#xC5D0; &#xC720;&#xC804;&#xC801; &#xBC30;&#xACBD;&#xC758; &#xC911;&#xC694;&#xC131;&#xC744; &#xACC4;&#xC2DC; &#xD558; &#xACE0; PfRh2a, Pfrh2b&#xC758; &#xACF5;&#xB3D9; &#xC2DD; &#xD568;&#xAED8; &#xD6A8;&#xC728;&#xC801;&#xC778; sialic &#xC0B0; &#xB3C5;&#xB9BD;&#xC801;&#xC778; &#xC801;&#xD608;&#xAD6C; &#xCE68;&#xACF5; &#xC911;&#xC7AC;&#xB294; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;.

Plasmodium falciparum &#xC801;&#xD608;&#xAD6C;&#xC5D0; &#xCE68;&#xC785;&#xC5D0; &#xB300; &#xD55C; &#xC811;&#xCC29; &#xB2E8;&#xBC31;&#xC9C8; &#xC0AC;&#xC774; cooperativity.

Plasmodium falciparum es el m&aacute;s virulento de las especies de plasmodios contagiosa a los seres humanos. Las cepas de p. falciparum diferentes var&iacute;an en su dependencia de los receptores del eritrocito para la invasi&oacute;n y su capacidad para cambiar en su utilizaci&oacute;n de repertorios diferentes receptores. Miembros de la familia de (RBL) protein&aacute;ceo reticulocitos Uni&oacute;n de ligandos de invasi&oacute;n se postulan para jugar un papel central en la definici&oacute;n de interacci&oacute;n ligando-receptor, conocido como caminos de invasi&oacute;n. Aqu&iacute; divulgamos la alteraci&oacute;n de genes espec&iacute;ficos de PfRh2b y PfRh2a en W2mef, una variedad de par&aacute;sitos que es fuertemente dependiente de &aacute;cidos si&aacute;licos receptores para la invasi&oacute;n y mostrar que el ligando PfRh2b es funcional en el fondo de este par&aacute;sito. Como la l&iacute;nea parental, par&aacute;sitos que carecen de PfRh2a o PfR2b pueden cambiar a un camino independiente de &aacute;cido si&aacute;lico invasi&oacute;n. Sin embargo, tanto de las l&iacute;neas conmutadas presentan una eficacia reducida de invasi&oacute;n en las c&eacute;lulas de &aacute;cido si&aacute;lico-agotado, sugiriendo un papel para PfRh2b y PfRh2a en invasi&oacute;n a trav&eacute;s de receptores de &aacute;cido si&aacute;lico independiente. Tambi&eacute;n encontramos una fuerte presi&oacute;n selectiva para la reconstituci&oacute;n de la expresi&oacute;n de PfRh2b a costa de PfRh2a. Nuestros resultados muestran la importancia del fondo gen&eacute;tico en uso ligando-receptor por p. falciparum par&aacute;sitos y sugieren que la expresi&oacute;n coordinada de PfRh2a, PfRh2b juntos mediar invasi&oacute;n eficiente de &aacute;cido si&aacute;lico independiente de eritrocito.

Cooperatividad entre prote&iacute;nas adhesivas de Plasmodium falciparum por invasi&oacute;n en eritrocitos.

&#x6211;&#x4EEC;&#x611F;&#x5174;&#x8DA3;&#x5929;&#x51AC;&#x9170;&#x80FA;-&#x805A;&#x7CD6; (N-&#x805A;&#x7CD6;&#xFF09; &#x7684;&#x6076;&#x6027;&#x759F;&#x539F;&#x866B;&#x548C;&#x5F13;&#x5F62;&#x866B;&#x7684;&#x56E0;&#x4E3A;&#x5B83;&#x4EEC;&#x7684; N-&#x8FDE;&#x63A5;&#x7CD6;&#x7ED3;&#x6784;&#x4E00;&#x76F4;&#x6709;&#x4E89;&#x8BAE;&#xFF0C;&#x56E0;&#x4E3A;&#x6211;&#x4EEC;&#x63A8;&#x6D4B;&#xFF0C;&#x53EF;&#x80FD;&#x5BF9; N-&#x805A;&#x7CD6;&#x5FC5;&#x987B;&#x7ECF;&#x8FC7;&#x5185;&#x8D28;&#x7F51; &#xFF08;ER&#xFF09; &#x4E4B;&#x524D;&#x7EBF;&#x7A0B;&#x8FDB;&#x5165; apicoplast &#x7684;&#x6838;&#x5FC3;&#x7F16;&#x7801;&#x86CB;&#x767D;&#x8D28;&#x4E2D;&#x7684;&#x9009;&#x5B9A;&#x5185;&#x5BB9;&#x3002;&#x652F;&#x6301;&#x6211;&#x4EEC;&#x7684;&#x5047;&#x8BBE;&#xFF0C;&#x6211;&#x4EEC;&#x8BA4;&#x4E3A;&#x4EE5;&#x4E0B;&#x3002;&#x9996;&#x5148;&#xFF0C;&#x4E0E; apicoplasts &#x7684;&#x751F;&#x7269;&#x4F53;&#xFF0C;&#x662F;&#x5411; N-&#x805A;&#x7CD6;&#x8102;&#x8D28;&#x94FE;&#x63A5;&#x524D;&#x4F53;&#x7684; Alg &#x9176;&#x5E7F;&#x6CDB;&#x4E8C;&#x6B21;&#x635F;&#x5931;&#x3002;&#x6CF0;&#x52D2;&#x4F7F;&#x6CA1;&#x6709; N-&#x805A;&#x7CD6;&#x5E76;&#x4E14;&#x759F;&#x539F;&#x866B;&#x4E25;&#x91CD;&#x88AB;&#x622A;&#x65AD;&#x7684; N-&#x8FDE;&#x63A5;&#x7CD6;&#x524D;&#x4F53;&#x7EC4;&#x6210;&#x7684;&#x4E00;&#x4E2A;&#x6216;&#x4E24;&#x4E2A;&#x5E38;&#x6CF0;&#x6B8B;&#x7559;&#x7269;&#x3002;&#x7B2C;&#x4E8C;&#xFF0C;&#x5206;&#x6CCC;&#x7684;&#x5F13;&#x5F62;&#xFF0C;&#x5B83;&#x4F7F;&#x7528;&#x81EA;&#x5DF1; 10 &#x7CD6;&#x524D;&#x4F53;&#x86CB;&#x767D; (Glc(3)Man(5)GlcNAc(2)) &#x548C;&#x4E3B;&#x673A; 14 &#x7CD6;&#x524D;&#x4F53; (Glc(3)Man(9)GlcNAc(2))&#xFF0C;&#x4F7F; N-&#x805A;&#x7CD6;&#xFF0C;&#x6709;&#x5F88;&#x5C11;&#x7684;&#x571F;&#x5730; N &#x7CD6;&#x57FA;&#x5316;&#xFF0C;&#x800C;&#x4E14;&#x6709;&#x9488;&#x5BF9;&#x5176; apicoplast &#x76EE;&#x6807;&#x86CB;&#x767D;&#x7684; N-&#x8FDE;&#x63A5;&#x7CD6;&#x7AD9;&#x70B9;&#x7684;&#x5176;&#x4ED6;&#x9009;&#x62E9;&#x3002;&#x7B2C;&#x4E09;&#xFF0C;&#x867D;&#x7136;&#x5E38;&#x6CF0;&#x7ED1;&#x5B9A; Griffonia simplicifolia &#x51DD;&#x96C6;&#x7D20; II &#x6807;&#x7B7E; ER&#x3001; rhoptries &#x548C;&#x759F;&#x539F;&#x866B;&#x7684;&#x8868;&#x9762;&#xFF0C;&#x6709;&#x6CA1;&#x6709; apicoplast &#x6807;&#x7B7E;&#x3002;&#x540C;&#x6837;&#xFF0C;&#x6297;&#x9006;&#x8F6C;&#x5F55;&#x75C5;&#x6BD2;&#x7597;&#x6CD5;&#x51DD;&#x96C6;&#x7D20;&#x84DD;&#x85FB;-N&#xFF0C;&#x5B83;&#x7ED1;&#x5B9A;&#x5230; N-&#x805A;&#x7CD6;&#x7684;&#x5F13;&#x5F62;&#x866B;&#x3001; &#x6807;&#x7B7E; ER &#x548C; rhoptries&#xFF0C;&#x4F46;&#x6709;&#x6CA1;&#x6709; apicoplast &#x6807;&#x7B7E;&#x3002;&#x6211;&#x4EEC;&#x5F97;&#x51FA;&#x7684;&#x7ED3;&#x8BBA;&#x53EF;&#x80FD;&#x7684;&#x9009;&#x62E9;&#xFF0C;&#x5BF9; N-&#x805A;&#x7CD6; apicoplasts &#x4E0E;&#x751F;&#x7269;&#x4F53;&#x4E2D;&#x53D1;&#x751F;&#x901A;&#x8FC7;&#x6D88;&#x9664; N-&#x805A;&#x7CD6; (&#x6CF0;&#x52D2;)&#x3001; &#x51CF;&#x5C11;&#x5176;&#x957F;&#x5EA6; &#xFF08;&#x759F;&#x539F;&#x866B;&#xFF09;&#xFF0C;&#x6216;&#x51CF;&#x5C11; N-&#x8FDE;&#x63A5;&#x7CD6;&#x7AD9;&#x70B9; &#xFF08;&#x5F13;&#x5F62;&#x866B;&#xFF09; &#x7684;&#x6570;&#x91CF;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x5360;&#x9886;&#x7684; N-&#x8FDE;&#x63A5;&#x7CD6;&#x7F51;&#x7AD9;&#x7684; apicoplast &#x86CB;&#x767D;&#x8D28;&#x4E0E;&#x4E00;&#x4E9B;&#x5206;&#x6CCC;&#x86CB;&#x767D;&#x7684;&#x759F;&#x539F;&#x866B;&#x548C;&#x5F13;&#x5F62;&#x866B;&#x663E;&#x8457;&#x964D;&#x4F4E;&#x3002;

&#x8FBE;&#x5C14;&#x6587;&#x9009;&#x62E9;&#x5BF9;&#x5929;&#x51AC;&#x9170;&#x80FA;-&#x805A;&#x7CD6;&#x7684;&#x6076;&#x6027;&#x759F;&#x539F;&#x866B;&#x548C;&#x5F13;&#x5F62;&#x866B;&#x7684;&#x6697;&#x793A;&#x6027;&#x8BC1;&#x636E;&#x3002;

We are interested in asparagine-linked glycans (N-glycans) of Plasmodium falciparum and Toxoplasma gondii, because their N-glycan structures have been controversial and because we hypothesize that there might be selection against N-glycans in nucleus-encoded proteins that must pass through the endoplasmic reticulum (ER) prior to threading into the apicoplast. In support of our hypothesis, we observed the following. First, in protists with apicoplasts, there is extensive secondary loss of Alg enzymes that make lipid-linked precursors to N-glycans. Theileria makes no N-glycans, and Plasmodium makes a severely truncated N-glycan precursor composed of one or two GlcNAc residues. Second, secreted proteins of Toxoplasma, which uses its own 10-sugar precursor (Glc(3)Man(5)GlcNAc(2)) and the host 14-sugar precursor (Glc(3)Man(9)GlcNAc(2)) to make N-glycans, have very few sites for N glycosylation, and there is additional selection against N-glycan sites in its apicoplast-targeted proteins. Third, while the GlcNAc-binding Griffonia simplicifolia lectin II labels ER, rhoptries, and surface of plasmodia, there is no apicoplast labeling. Similarly, the antiretroviral lectin cyanovirin-N, which binds to N-glycans of Toxoplasma, labels ER and rhoptries, but there is no apicoplast labeling. We conclude that possible selection against N-glycans in protists with apicoplasts occurs by eliminating N-glycans (Theileria), reducing their length (Plasmodium), or reducing the number of N-glycan sites (Toxoplasma). In addition, occupation of N-glycan sites is markedly reduced in apicoplast proteins versus some secretory proteins in both Plasmodium and Toxoplasma.

Suggestive evidence for Darwinian Selection against asparagine-linked glycans of Plasmodium falciparum and Toxoplasma gondii.

Nous sommes int&#xE9;ress&#xE9;s par glycanes li&#xE9;s &#xE0; l&#x26;#39;asparagine (N-glycanes) de Plasmodium falciparum et Toxoplasma gondii, parce que leurs structures glycanniques N-ont suscit&#xE9; la controverse et parce que nous faisons l&#x26;#39;hypoth&#xE8;se qu&#x26;#39;il pourrait y avoir une s&#xE9;lection contre N-glycanes dans le noyau de prot&#xE9;ines cod&#xE9;es par qui doit passer &#xE0; travers le r&#xE9;ticulum endoplasmique (RE) avant le filetage dans le apicoplaste. &#xC0; l&#x26;#39;appui de notre hypoth&#xE8;se, nous avons observ&#xE9; ce qui suit. Tout d&#x26;#39;abord, dans les protistes avec apicoplastes, il ya une vaste perte secondaire de Alg enzymes qui font des lipides li&#xE9;s pr&#xE9;curseurs de N-glycanes. Theileria fait pas N-glycannes, et Plasmodium fait une fortement tronqu&#xE9;e N-glycane pr&#xE9;curseur compos&#xE9; de un ou deux r&#xE9;sidus GlcNAc. Deuxi&#xE8;mement, les prot&#xE9;ines s&#xE9;cr&#xE9;t&#xE9;es de Toxoplasma, qui utilise son propre 10-sucre pr&#xE9;curseur (Glc (3) L&#x26;#39;homme (5) GlcNAc (2)) et l&#x26;#39;h&#xF4;te de 14 sucre pr&#xE9;curseur (Glc (3) L&#x26;#39;homme (9) GlcNAc (2)) faire N-glycannes, ont des sites de glycosylation tr&#xE8;s peu de N, et il est de s&#xE9;lection suppl&#xE9;mentaire contre le N-glycane sites dans ses prot&#xE9;ines apicoplaste cibl&#xE9;es. Troisi&#xE8;mement, alors que la GlcNAc-contraignant Griffonia simplicifolia lectine &#xE9;tiquettes II ER, rhoptries, et la surface de plasmodies, il n&#x26;#39;y a pas d&#x26;#39;&#xE9;tiquetage apicoplaste. De m&#xEA;me, la lectine antir&#xE9;troviral cyanovirine-N, qui se lie &#xE0; N-glycanes de Toxoplasma ER, les &#xE9;tiquettes et rhoptries, mais il n&#x26;#39;ya pas d&#x26;#39;&#xE9;tiquetage apicoplaste. Nous concluons que la s&#xE9;lection possible contre N-glycanes dans les protistes avec apicoplastes se produit en &#xE9;liminant N-glycanes (Theileria), la r&#xE9;duction de leur longueur (Plasmodium), ou en r&#xE9;duisant le nombre de sites de N-glycanes (Toxoplasma). En outre, l&#x26;#39;occupation de la N-glycanes des sites est nettement r&#xE9;duite en prot&#xE9;ines par rapport apicoplaste certaines prot&#xE9;ines s&#xE9;cr&#xE9;toires &#xE0; la fois Plasmodium et Toxoplasma.

Des &#xE9;l&#xE9;ments qui sugg&#xE8;rent pour la s&#xE9;lection darwinienne contre asparagine-glycanes de Plasmodium falciparum et Toxoplasma gondii

Wir sind interessiert an Asparagin-chromosomale Glykane (N-Glykane) von Plasmodium Falciparum und Toxoplasma Gondii, weil ihre N-Glykan-Strukturen umstritten gewesen und wir, dass vermuten es m&ouml;glicherweise Auswahl gegen N-Glykane im Zellkern kodierten Proteine, die das Endoplasmatisches Reticulum (ER) vor threading in den Apicoplast durchlaufen m&uuml;ssen. Zur Unterst&uuml;tzung unserer Hypothese beobachteten wir im folgenden. Erstens gibt es in Einzellern mit Apicoplasts, umfangreichen sekund&auml;ren Verlust Alg-Enzyme, die Lipid-chromosomale Vorstufen an N-Glykane vornehmen. Theileria macht keine N-Glykane und Plasmodium macht eine stark gek&uuml;rzte N-Glykan-Vorstufe setzt sich aus einem oder zwei GlcNAc-R&uuml;ckst&auml;nde. Zweitens abgesondert Proteine von Toxoplasma, die Vorl&auml;ufer der 10-Zucker verwendet (Glc(3)Man(5)GlcNAc(2)) und Vorl&auml;ufer der Host-14-Zucker (Glc(3)Man(9)GlcNAc(2)) N-Glykane, machen haben sehr wenige Sites f&uuml;r N-Glycosylation und zus&auml;tzliche Auswahl gegen N-Glykan Orte in seiner Apicoplast ausgerichtete Proteine vorhanden ist. Drittens, w&auml;hrend die GlcNAc-Bindung Griffonia Simplicifolia Lektin II ER, Rhoptries und Oberfl&auml;che der Plasmodien Etiketten, gibt es keine Apicoplast bezeichnen. Ebenso die antiretrovirale Lektin Cyanovirin-N, die an N-Glykane von Toxoplasma, Etiketten ER und Rhoptries bindet, aber es keine Apicoplast gibt bezeichnen. Wir schlie&szlig;en, dass die m&ouml;gliche Auswahl gegen N-Glykane in Einzellern mit Apicoplasts tritt durch die Beseitigung von N-Glykanen (Theileria), reduzieren ihre L&auml;nge (Plasmodium) oder Reduzierung der Anzahl der N-Glykan-Websites (Toxoplasma). Dar&uuml;ber hinaus ist Beruf N-Glykan-Sites in Apicoplast Proteine im Vergleich zu einigen sekretorischen Proteinen in Plasmodium und Toxoplasma deutlich reduziert.

Suggestive Beweise f&uuml;r die darwinistische Auswahl gegen Asparagin-chromosomale Glykane von Plasmodium Falciparum und Toxoplasma Gondii.

Siamo interessati a legato asparagina glicani (N-glicani) del Plasmodium falciparum e Toxoplasma gondii, perch&eacute; loro strutture N-glycan sono stati controverse e Ipotizziamo che ci potrebbe essere la selezione contro N-glicani in proteine codificate dal nucleo che deve passare attraverso il reticolo endoplasmatico (ER) prima di threading nella apicoplast. A sostegno della nostra ipotesi, abbiamo osservato quanto segue. In primo luogo, nei protisti con apicoplasts, c&#39;&egrave; una vasta perdita secondaria di Alg enzimi che rendono precursori lipidica legata a N-glicani. Theileria non rende N-glicani, e Plasmodium rende gravemente troncato N-glycan precursore composto da uno o due residui GlcNAc. Secreto in secondo luogo, le proteine di Toxoplasma, che utilizza il proprio precursore 10-zucchero (Glc(3)Man(5)GlcNAc(2)) e il precursore di zucchero 14 ospite (Glc(3)Man(9)GlcNAc(2)) fare N-glicani, hanno pochissimi siti di glicosilazione N, e non c&#39;&egrave; selezione supplementare contro i siti di N-glycan nella sue proteine apicoplast mirati. In terzo luogo, mentre il GlcNAc-associazione Griffonia simplicifolia lectina II etichette ER, rhoptries con superficie di plasmodi, non non c&#39;&egrave; nessun apicoplast di etichettatura. Allo stesso modo, l&#39;antiretrovirale lectina cyanovirin-N, che si lega al N-glicani del Toxoplasma, etichette ER e rhoptries, ma non non c&#39;&egrave; nessun apicoplast di etichettatura. Possiamo concludere che la possibile scelta contro N-glicani in protisti con apicoplasts avviene eliminando N-glicani (Theileria), riducendo la loro lunghezza (Plasmodium), o riducendo il numero di siti di N-glycan (Toxoplasma). Inoltre, occupazione dei siti di N-glycan &egrave; marcatamente ridotta in proteine apicoplast contro alcune proteine secretorie in Plasmodium e Toxoplasma.

Suggestiva prova per selezione darwiniana contro legato asparagina glicani del Plasmodium falciparum e Toxoplasma gondii.

&#x305D;&#x308C;&#x3089;&#x306E;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x69CB;&#x9020;&#x304C;&#x8B70;&#x8AD6;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x305F;&#x3081;&#x3001;&#x6211;&#x3005;&#x304C;&#x901A;&#x904E;&#x3057;&#x306A;&#x3051;&#x308C;&#x3070;&#x306A;&#x3089;&#x306A;&#x3044;&#x6838;&#x3067;&#x30A8;&#x30F3;&#x30B3;&#x30FC;&#x30C9;&#x3055;&#x308C;&#x305F;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306B;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x9078;&#x629E;&#x304C;&#x3042;&#x308B;&#x304B;&#x3082;&#x3057;&#x308C;&#x306A;&#x3044;&#x3068;&#x3044;&#x3046;&#x4EEE;&#x8AAC;&#x3092;&#x7ACB;&#x3066;&#x305F;&#x306E;&#x3067;&#x3001;&#x6211;&#x3005;&#x306F;&#x3001;&#x71B1;&#x5E2F;&#x71B1;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x539F;&#x866B;&#x3068;&#x30C8;&#x30AD;&#x30BD;&#x30D7;&#x30E9;&#x30BA;&#x30DE;&#x306E;&#x30A2;&#x30B9;&#x30D1;&#x30E9;&#x30AE;&#x30F3;&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#xFF08;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#xFF09;&#x306B;&#x8208;&#x5473;&#x304C;&#x3042;&#x308B;&#x5C0F;&#x80DE;&#x4F53;&#xFF08;ER&#xFF09;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x4E8B;&#x524D;apicoplast&#x306B;&#x30B9;&#x30EC;&#x30C3;&#x30C9;&#x3078;&#x3002;&#x6211;&#x3005;&#x306E;&#x4EEE;&#x8AAC;&#x3092;&#x30B5;&#x30DD;&#x30FC;&#x30C8;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x3001;&#x6211;&#x3005;&#x306F;&#x4EE5;&#x4E0B;&#x3092;&#x89B3;&#x5BDF;&#x3057;&#x305F;&#x3002;&#x307E;&#x305A;&#x3001;apicoplasts&#x3068;&#x539F;&#x751F;&#x751F;&#x7269;&#x3067;&#x306F;&#x3001;N-&#x30B0;&#x30EA;&#x30AB;&#x30F3;&#x306B;&#x8102;&#x8CEA;&#x67B6;&#x6A4B;&#x524D;&#x99C6;&#x4F53;&#x3092;&#x4F5C;&#x308B;&#x9175;&#x7D20;&#x3092;ALG&#x306E;&#x5E83;&#x7BC4;&#x306A;&#x4E8C;&#x6B21;&#x640D;&#x5931;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x30BF;&#x30A4;&#x30EC;&#x30EA;&#x30A2;&#x306F;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x3092;&#x884C;&#x3044;&#x307E;&#x305B;&#x3093;&#x3057;&#x3001;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x539F;&#x866B;&#x306F;&#x3001;1&#x3064;&#x307E;&#x305F;&#x306F;2&#x3064;&#x306E;GlcNAc&#x6B8B;&#x57FA;&#x304B;&#x3089;&#x6210;&#x308B;&#x53B3;&#x3057;&#x304F;&#x5207;&#x308A;&#x8A70;&#x3081;&#x3089;&#x308C;&#x305F;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x524D;&#x99C6;&#x4F53;&#x306B;&#x306A;&#x308A;&#x307E;&#x3059;&#x3002;&#x72EC;&#x81EA;&#x306E;10-&#x7CD6;&#x524D;&#x99C6;&#x4F53;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x30C8;&#x30AD;&#x30BD;&#x30D7;&#x30E9;&#x30BA;&#x30DE;&#x7B2C;&#x4E8C;&#x306B;&#x3001;&#x5206;&#x6CCC;&#x3055;&#x308C;&#x308B;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x3001;&#xFF08;GLC&#xFF08;3&#xFF09;&#x7537;&#xFF08;5&#xFF09;&#x30B0;&#x30EB;&#x30B3;&#x30B5;&#x30DF;&#x30F3;&#xFF08;2&#xFF09;&#xFF09;&#x3068;&#x30DB;&#x30B9;&#x30C8;14-&#x7CD6;&#x524D;&#x99C6;&#x4F53;&#xFF08;GLC&#xFF08;3&#xFF09;&#x7537;&#xFF08;9&#xFF09;&#x30B0;&#x30EB;&#x30B3;&#x30B5;&#x30DF;&#x30F3;&#xFF08;2&#xFF09;&#xFF09; N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x3092;&#x4F5C;&#x308B;&#x305F;&#x3081;&#x306B;&#x3001;N&#x500B;&#x306E;&#x30B0;&#x30EA;&#x30B3;&#x30B7;&#x30EB;&#x5316;&#x306E;&#x305F;&#x3081;&#x306E;&#x975E;&#x5E38;&#x306B;&#x3044;&#x304F;&#x3064;&#x304B;&#x306E;&#x30B5;&#x30A4;&#x30C8;&#x3092;&#x6301;&#x3063;&#x3066;&#x304A;&#x308A;&#x3001;&#x305D;&#x306E;apicoplast&#x6A19;&#x7684;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306E;N-&#x30B0;&#x30EA;&#x30AB;&#x30F3;&#x306E;&#x30B5;&#x30A4;&#x30C8;&#x306B;&#x5BFE;&#x3057;&#x3066;&#x3001;&#x8FFD;&#x52A0;&#x306E;&#x9078;&#x629E;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002; GlcNAc&#x3092;&#x7D50;&#x5408;Griffonia simplicifolia&#x30EC;&#x30AF;&#x30C1;&#x30F3;II&#x30E9;&#x30D9;&#x30EB;ER&#x3001;rhoptries&#x3001;&#x3068;&#x5909;&#x5F62;&#x4F53;&#x306E;&#x8868;&#x9762;&#x306E;&#x9593;&#x306B;&#x7B2C;&#x4E09;&#x306B;&#x3001;&#x4F55;apicoplast&#x6A19;&#x8B58;&#x306F;&#x3042;&#x308A;&#x307E;&#x305B;&#x3093;&#x3002;&#x540C;&#x69D8;&#x306B;&#x3001;&#x6297;&#x30EC;&#x30C8;&#x30ED;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x85AC;&#x30C8;&#x30AD;&#x30BD;&#x30D7;&#x30E9;&#x30BA;&#x30DE;&#x3001;&#x30E9;&#x30D9;&#x30EB;&#x3001;ER&#x3068;rhoptries&#x306E;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x306B;&#x7D50;&#x5408;&#x3059;&#x308B;&#x30EC;&#x30AF;&#x30C1;&#x30F3;cyanovirin-N&#x3001;&#x304C;&#x3001;&#x305D;&#x3053;&#x306F;apicoplast&#x30E9;&#x30D9;&#x30EA;&#x30F3;&#x30B0;&#x3067;&#x306F;&#x3042;&#x308A;&#x307E;&#x305B;&#x3093;&#x3002; apicoplasts&#x3068;&#x539F;&#x751F;&#x751F;&#x7269;&#x306E;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x306B;&#x5BFE;&#x3057;&#x3066;&#x53EF;&#x80FD;&#x200B;&#x200B;&#x306A;&#x304B;&#x304E;&#x308A;&#x9078;&#x629E;&#x3059;&#x308B;&#x3068;&#x3001;&#x305D;&#x306E;&#x9577;&#x3055;&#xFF08;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#xFF09;&#x3092;&#x524A;&#x6E1B;&#x3001;&#x307E;&#x305F;&#x306F;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x90E8;&#x4F4D;&#xFF08;&#x30C8;&#x30AD;&#x30BD;&#x30D7;&#x30E9;&#x30BA;&#x30DE;&#xFF09;&#x306E;&#x6570;&#x3092;&#x6E1B;&#x3089;&#x3057;&#x3001;N-&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#xFF08;&#x30BF;&#x30A4;&#x30EC;&#x30EA;&#x30A2;&#xFF09;&#x3092;&#x6392;&#x9664;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x767A;&#x751F;&#x3057;&#x305F;&#x6211;&#x3005;&#x306F;&#x7D50;&#x8AD6;&#x3059;&#x308B;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;N&#x578B;&#x7CD6;&#x9396;&#x90E8;&#x4F4D;&#x306E;&#x8077;&#x696D;&#x304C;&#x8457;&#x3057;&#x304F;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x3084;&#x30C8;&#x30AD;&#x30BD;&#x30D7;&#x30E9;&#x30BA;&#x30DE;&#x306E;&#x4E21;&#x65B9;&#x3067;&#x3044;&#x304F;&#x3064;&#x304B;&#x306E;&#x5206;&#x6CCC;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x5BFE;apicoplast&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306B;&#x524A;&#x6E1B;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;

&#x71B1;&#x5E2F;&#x71B1;&#x30DE;&#x30E9;&#x30EA;&#x30A2;&#x539F;&#x866B;&#xFF08;Plasmodium falciparum&#xFF09;&#x3084;&#x30C8;&#x30AD;&#x30BD;&#x30D7;&#x30E9;&#x30BA;&#x30DE;&#x539F;&#x866B;&#x306E;&#x30A2;&#x30B9;&#x30D1;&#x30E9;&#x30AE;&#x30F3;&#x7D50;&#x5408;&#x578B;&#x7CD6;&#x9396;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x30C0;&#x30FC;&#x30A6;&#x30A3;&#x30F3;&#x306E;&#x9078;&#x629E;&#x306E;&#x305F;&#x3081;&#x306E;&#x793A;&#x5506;&#x3059;&#x308B;&#x8A3C;&#x62E0;

&#xC6B0;&#xB9AC;&#xB294; Plasmodium falciparum Toxoplasma gondii&#xC758; &#xC544;&#xC2A4;&#xD30C;&#xB77C;&#xAE34; &#xC5F0;&#xACB0; &#xB41C; glycans (N glycans)&#xC5D0; &#xAD00;&#xC2EC;&#xC774; &#xADF8;&#xB4E4;&#xC758; N glycan &#xAD6C;&#xC870; &#xB17C;&#xB780;&#xC774; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4; &#xADF8;&#xB9AC;&#xACE0; &#xC6B0;&#xB9AC;&#xB294; &#xAC00;&#xC124;&#xC744; &#xC2A4;&#xB808;&#xB529; &#xC774;&#xC804; endoplasmic &#xADF8;&#xBB3C; (ER)&#xB294; apicoplast&#xB85C; &#xD1B5;&#xACFC; &#xD574;&#xC57C; &#xD575; &#xC778;&#xCF54;&#xB529; &#xB2E8;&#xBC31;&#xC9C8;&#xC758; N-glycans&#xC5D0; &#xB300; &#xD55C; &#xC120;&#xD0DD; &#xC788;&#xC744; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xC758; &#xAC00;&#xC124;&#xC744; &#xC9C0; &#xC6D0;&#xD558;&#xB294; &#xB2E4;&#xC74C; &#xAD00;&#xCC30;&#xD569;&#xB2C8;&#xB2E4;. &#xCCAB;&#xC9F8;, apicoplasts&#xC640; protists, N-glycans&#xC5D0; &#xAC8C; &#xC9C0;&#xC9C8; &#xC5F0;&#xACB0; &#xC120;&#xAD6C;&#xC790; Alg &#xD6A8;&#xC18C;&#xC758; &#xAD11;&#xBC94;&#xC704; &#xD55C; &#xBCF4;&#xC870; &#xC190;&#xC2E4;&#xC774; &#xC774;&#xB2E4;. Theileria N glycans &#xC5C6;&#xC2B5;&#xB2C8;&#xB2E4; &#xB9CC;&#xB4E4;&#xACE0; Plasmodium &#xC2EC;&#xAC01; &#xD558; &#xAC8C; &#xC798;&#xB9B0;&#xB41C; N glycan &#xC804;&#xC870; &#xD558; &#xAC8C; &#xD558;&#xB098; &#xB610;&#xB294; &#xB450; &#xAC1C;&#xC758; GlcNAc &#xC794;&#xB958;&#xBB3C;&#xC758; &#xAD6C;&#xC131;. &#xB458;&#xC9F8;, Toxoplasma &#xC790;&#xCCB4; 10 &#xC124;&#xD0D5; &#xC804;&#xC870;&#xB97C; &#xC0AC;&#xC6A9; &#xD558;&#xB294; &#xB2E8;&#xBC31;&#xC9C8;&#xC744; &#xBD84; &#xBE44; (Glc(3)Man(5)GlcNAc(2)) &#xBC0F; &#xD638;&#xC2A4;&#xD2B8; 14 &#xC124;&#xD0D5; &#xC804;&#xC870; (Glc(3)Man(9)GlcNAc(2)) N glycans&#xC744;&#xAC00;&#xC9C0;&#xACE0; N glycosylation &#xAC70;&#xC758; &#xC0AC;&#xC774;&#xD2B8; &#xBC0F; apicoplast &#xD0C0;&#xAC9F; &#xB2E8;&#xBC31;&#xC9C8;&#xC758; N-glycan &#xC0AC;&#xC774;&#xD2B8;&#xC5D0; &#xB300; &#xD55C; &#xCD94;&#xAC00; &#xC120;&#xD0DD;&#xC774; &#xC788;&#xB2E4;. &#xC14B;&#xC9F8;, GlcNAc &#xBC14;&#xC778;&#xB529; Griffonia simplicifolia lectin II &#xB808;&#xC774;&#xBE14; ER, rhoptries, &#xADF8;&#xB9AC;&#xACE0; plasmodia&#xC758; &#xD45C;&#xBA74;, &#xD558;&#xB294; &#xB3D9;&#xC548;&#xC5D0; &#xAC70;&#xAE30; &#xC544;&#xBB34; apicoplast&#xB294; &#xB77C;&#xBCA8;. &#xB9C8;&#xCC2C;&#xAC00;&#xC9C0;&#xB85C;, &#xD56D; &#xB808;&#xD2B8;&#xB85C; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; lectin cyanovirin-N, Toxoplasma, &#xB77C;&#xBCA8; &#xC751;&#xAE09;&#xC2E4; &#xBC0F; rhoptries&#xC758; N-glycans&#xB97C; &#xBC14;&#xC778;&#xB529;&#xD558;&#xB294; &#xC788;&#xC9C0;&#xB9CC; &#xC5C6;&#xC2B5;&#xB2C8;&#xB2E4; apicoplast &#xB77C;&#xBCA8;. &#xC6B0;&#xB9AC;&#xAC00; &#xACB0;&#xB860;&#xC744; apicoplasts&#xC640; protists&#xC5D0;&#xC11C; N-glycans&#xC5D0; &#xB300; &#xD55C; &#xAC00;&#xB2A5;&#xD55C; &#xC120;&#xD0DD; N-glycans (Theileria)&#xC744; &#xC81C;&#xAC70;, &#xADF8;&#xB4E4;&#xC758; &#xAE38;&#xC774; (Plasmodium) &#xAC10;&#xC18C; &#xB610;&#xB294; N glycan &#xC0AC;&#xC774;&#xD2B8; (Toxoplasma)&#xC758; &#xC218;&#xB97C; &#xAC10;&#xC18C; &#xD558; &#xC5EC; &#xBC1C;&#xC0DD; &#xD569;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, N glycan &#xC0AC;&#xC774;&#xD2B8;&#xC758; &#xC9C1;&#xC5C5; Plasmodium&#xC5D0; Toxoplasma &#xC5B4;&#xB5A4; &#xBD84; &#xB2E8;&#xBC31;&#xC9C8; &#xB300; apicoplast &#xB2E8;&#xBC31;&#xC9C8;&#xC5D0; &#xD604;&#xC800; &#xD558; &#xAC8C; &#xC904;&#xC5B4;&#xB4ED;&#xB2C8;&#xB2E4;.

Plasmodium falciparum Toxoplasma gondii&#xC758; &#xC544;&#xC2A4;&#xD30C;&#xB77C;&#xAE34; &#xC5F0;&#xACB0; &#xB41C; glycans&#xC5D0; &#xB300; &#xD55C; &#xB2E4;&#xC708; &#xC120;&#xD0DD;&#xC5D0; &#xB300; &#xD55C; &#xC99D;&#xAC70;&#xB97C; &#xC554;&#xC2DC;.

Estamos interesados &#x200B;&#x200B;en glicanos ligados a asparagina (N-glicanos) de Plasmodium falciparum y Toxoplasma gondii, porque sus N-glicanos estructuras han sido motivo de controversia y debido a que la hip&#xF3;tesis de que puede haber selecci&#xF3;n en contra de N-glicanos de las prote&#xED;nas codificadas en el n&#xFA;cleo-que deben pasar a trav&#xE9;s del ret&#xED;culo endoplasm&#xE1;tico (ER) antes de roscar en la apicoplast. En apoyo de nuestra hip&#xF3;tesis, se observ&#xF3; lo siguiente. En primer lugar, en los protistas con apicoplasts, hay una gran p&#xE9;rdida secundaria de Alg enzimas que hacen que los l&#xED;pidos vinculados a los precursores de N-glicanos. Theileria no hace N-glicanos, y Plasmodium hace una severamente truncada N-glicanos precursor compuesto por uno o dos residuos de GlcNAc. Prote&#xED;nas secretadas En segundo lugar, de Toxoplasma, que utiliza su propio 10-precursor de az&#xFA;car (Glc (3) Hombre (5) GlcNAc (2)) y el anfitri&#xF3;n de la 14-precursor de az&#xFA;car (Glc (3) Hombre (9) GlcNAc (2)) para hacer N-glicanos, tienen muy pocos sitios para glicosilaci&#xF3;n N, y hay una selecci&#xF3;n adicional contra la N-glicano sitios espec&#xED;ficos en sus apicoplast-prote&#xED;nas. En tercer lugar, mientras que la GlcNAc-uni&#xF3;n de Griffonia simplicifolia lectina II etiquetas ER, roptries, y la superficie de plasmodios, no hay etiquetado apicoplast. De manera similar, la lectina antirretroviral cyanovirin-N, que se une a N-glicanos de Toxoplasma, las etiquetas de ER y roptries, pero no hay etiquetado apicoplast. Se concluye que la selecci&#xF3;n posible contra N-glicanos en protistas con apicoplasts se produce mediante la eliminaci&#xF3;n de N-glicanos (Theileria), reduciendo su longitud (Plasmodium), o reduciendo el n&#xFA;mero de sitios de N-glicanos (Toxoplasma). Adem&#xE1;s, la ocupaci&#xF3;n de N-glicanos sitios se reduce notablemente en comparaci&#xF3;n con las prote&#xED;nas apicoplast algunas prote&#xED;nas secretoras, tanto en Plasmodium y Toxoplasma.

Evidencia que sugiere para la selecci&#xF3;n darwiniana contra vinculados asparagina-glicanos de Plasmodium falciparum y Toxoplasma gondii

Free κ L chains (FκLCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which FκLCs interact with membranes remains unresolved. In this study, we show that FκLCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound FκLCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of FκLCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated FκLCs exposed on the plasma membrane after exocytosis. Although it is well known that protein aggregates bind membranes, this is only the second example of an aggregate being found on the surface of cells that also secrete the protein in its native form. We postulate that many other aggregation-prone proteins may associate with cell membranes by similar mechanisms.

Free Ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form.

The murine mAb, K-1-21, recognizes a conformational epitope expressed on free Ig kappa light chains (FκLCs) and also on cell membrane-associated FκLCs found on kappa myeloma cells. This has led to the development of a chimeric version of K-1-21, MDX-1097, which is being assessed in a Phase II clinical trial for the treatment of multiple myeloma. The epitope recognized by K-1-21 is of particular interest, especially in the context that it is not expressed on heavy chain-associated light chains such as in an intact Ig molecule. Using epitope excision techniques we have localized the K-1-21 epitope to a region spanning residues 104-110 of FκLC. This short strand of residues links the variable and constant domains, and is a flexible region that adopts different conformations in FκLC and heavy chain-associated light chain. We tested this region using site-directed mutations and found that the reactivity of K-1-21 for FκLC was markedly reduced. Finally, we applied in silico molecular docking to generate a model that satisfied the experimental data. Given the clinical potential of the Ag, this study may aid the development of next generation compounds that target the membrane form of FκLC expressed on the surface of myeloma plasma cells.

Characterization of a unique conformational epitope on free immunoglobulin kappa light chains that is recognized by an antibody with therapeutic potential.

Decreased intervertebral disc (IVD) volume can result in diminished load-carrying capacity of the spinal region. Although moderate-intensity running is generally advocated for apparently healthy adults, running causes a loss in stature that is thought to reflect IVD compression. The aim of this investigation was to use magnetic resonance imaging (MRI) to quantify the influence of moderate-intensity treadmill running on IVD height and volume in the thoracic and lumbar regions of the vertebral column.

Moderate-intensity running causes intervertebral disc compression in young adults.

Although active gaming is popular and can increase energy expenditure in young adults, its efficacy as a prescriptive exercise tool is not well understood. This study aimed to: (a) compare the activity intensities experienced by young adults while playing active tennis gaming with conventional sedentary gaming, tennis game-play, and current activity recommendations for health; and (b) identify changes in activity intensities across playing time. After habitualization, 10 active young adults (age: 20.2 ± 0.4 years; stature: 1.74 ± 0.03 m; body mass: 67.7 ± 3.3 kg) completed 3 experimental trials (sedentary gaming, active tennis gaming, and tennis game-play) on separate days in a randomized order. Heart rate (HR) and metabolic equivalents (METs) were averaged across 5 minutes and 10 minutes intervals, and the entire 20 minutes bout within each condition. Active gaming produced greater intensities across 5-10, 10-15, and 15-20 minutes time intervals compared with sedentary gaming (p < 0.01). Tennis game-play elicited greater HR (67 ± 5% HR(max)) and METs (5.0 ± 0.2) responses than both sedentary (40 ± 2% HR(max), 1.1 ± 0.1 METs) and active gaming (45 ± 2% HR(max), 1.4 ± 0.1 METs) (p < 0.001). Only tennis game-play produced activity intensities meeting current recommendations for health benefit. Lower HR intensities were reached across 0-5 minutes than during later time intervals during active gaming (6%) and tennis game-play (9%) (p < 0.01). Activity intensities elicited by active gaming were greater than sedentary gaming but less than tennis game-play and insufficient to contribute toward promoting and maintaining good health in young adults. These data suggest that active tennis gaming should not be recommended by exercise professionals as a substitute for actual sports participation in young adults.

The activity intensities reached when playing active tennis gaming relative to sedentary gaming, tennis game-play, and current activity recommendations in young adults.

Article	Year
Conserved structural and sequence elements implicated in the processing of gene-encoded circular proteins. The Journal of biological chemistry\| PubMed ID: 15328347	2004
Isolation, solution structure, and insecticidal activity of kalata B2, a circular protein with a twist: do Möbius strips exist in nature? Biochemistry\| PubMed ID: 15654741	2005
Molecular analysis of erythrocyte invasion in Plasmodium falciparum isolates from Senegal. Infection and immunity\| PubMed ID: 17470537	2007
Biosynthesis of circular proteins in plants. The Plant journal : for cell and molecular biology\| PubMed ID: 18086282	2008
Erythrocyte invasion by Plasmodium falciparum: multiple ligand-receptor interactions and phenotypic switching. Sub-cellular biochemistry\| PubMed ID: 18512340	2008
Genetic analysis of the cytoplasmic domain of the PfRh2b merozoite invasion protein of Plasmodium falciparum. International journal for parasitology\| PubMed ID: 18831976	2009
Cooperativity between Plasmodium falciparum adhesive proteins for invasion into erythrocytes. Molecular microbiology\| PubMed ID: 19400777	2009
Suggestive evidence for Darwinian Selection against asparagine-linked glycans of Plasmodium falciparum and Toxoplasma gondii. Eukaryotic cell\| PubMed ID: 19783771	2010
Free Ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 20817866	2010
Characterization of a unique conformational epitope on free immunoglobulin kappa light chains that is recognized by an antibody with therapeutic potential. Molecular immunology\| PubMed ID: 21466897	2011
Moderate-intensity running causes intervertebral disc compression in young adults. Medicine and science in sports and exercise\| PubMed ID: 22648342	2012
The activity intensities reached when playing active tennis gaming relative to sedentary gaming, tennis game-play, and current activity recommendations in young adults. Journal of strength and conditioning research / National Strength & Conditioning Association\| PubMed ID: 23238089	2013

Cameron Jennings

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