highly-stereoselective-synthesis-16-ketoesters-mediated-ionic-liquids

Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators

In organic chemistry ionic liquids (ILs) have emerged as safe and recyclable reaction solvents. In the presence of a base ILs can be deprotonated to form ...

Chalmers University of Technology

The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs) is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (http://www.AltAnalyze.org), we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation.

Alternative splicing in the differentiation of human embryonic stem cells into cardiac precursors.

Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene mutations. We genotyped additional CDH patients for four of these six SNPs, including the three non-synonymous SNPs, to make a total of 200 chromosomes, and found that the allele frequency for the four SNPs, did not differ significantly between patients and normal controls (p > or = 0.05). We then used Affymetrix Genechip Mouse Gene 1.0 ST arrays and found eight genes with significantly reduced expression levels in the diaphragms of Fgfrl1 homozygous null mice when compared with wildtype mice-Tpm3, Fgfrl1 (p = 0.004), Myl2, Lrtm1, Myh4, Myl3, Myh7 and Hephl1. Lrtm1 is closely related to Slit3, a protein associated with herniation of the central tendon of the diaphragm in mice. The Slit proteins are known to regulate axon branching and cell migration, and inhibition of Slit3 reduces cell motility and decreases the expression of Rac and Cdc42, two genes that are essential for myoblast fusion. Further studies to determine if Lrtm1 has a similar function to Slit3 and if reduced Fgfrl1 expression can cause diaphragm hypoplasia through a mechanism involving decreased myoblast motility and/or myoblast fusion, seem indicated.

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm.

&#x5E7D;&#x95E8; pyloricag &#x81F4;&#x75C5;&#x5C9B; (cag PAI&#xFF09; &#x8FDB;&#x884C;&#x7F16;&#x7801;&#x66F4;&#x5E38;&#x89C1;&#x7684;&#x682A;&#x6BD4;&#x4ECE;&#x90A3;&#x4E9B;&#x65E0;&#x75C7;&#x72B6;&#x80C3;&#x708E;&#x7684;&#x80C3;&#x5341;&#x4E8C;&#x6307;&#x80A0;&#x75BE;&#x75C5;&#x60A3;&#x8005;&#x4ECE;&#x7C7B;&#x578B;&#x56DB;&#x3001; &#x5206;&#x6CCC;&#x7CFB;&#x7EDF;&#x3002;H.&#x87BA;&#x6746;&#x83CC;&#x83CC; 26695 &#x7684;&#x8F6C;&#x5F55;&#x5355;&#x4F4D;&#x7684;&#x5168;&#x57FA;&#x56E0;&#x7EC4;&#x7EC4;&#x7EC7;&#x6700;&#x8FD1;&#x6210;&#x7ACB;&#x4E86;&#x4F7F;&#x7528; RNA &#x5E8F;&#x5217;&#x5206;&#x6790; (&#x590F;&#x5C14;&#x9A6C; et al&#xFF0C;2010&#x5E74;)&#x3002;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x7528;&#x5B9A;&#x91CF;&#x9006;&#x8F6C;&#x5F55;-&#x805A;&#x5408;&#x9176;&#x94FE;&#x53CD;&#x5E94;&#x7684;&#x5F00;&#x653E;&#x9605;&#x8BFB;&#x6846;&#x67B6;&#x548C;&#x57FA;&#x56E0;&#x533A;&#x57DF;&#x6765;&#x6807;&#x8BC6;&#x5728;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC; &#xFF1B; &#x5047;&#x5B9A; cag PAI operons&#x901A;&#x8FC7;&#x5206;&#x6790;&#x8FD9;&#x4E9B; operons &#x8FDB;&#x4E00;&#x6B65;&#x7684;&#x8C08;&#x8BDD;&#x5185;&#x5BB9;&#x5206;&#x6790;&#x540E;&#x5220;&#x9664;&#x6240;&#x9009;&#x7684;&#x542F;&#x52A8;&#x5B50;&#x533A;&#x57DF;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x6211;&#x4EEC;&#x53EF;&#x4EE5;&#x4F7F;&#x7528;&#x542F;&#x52A8;&#x5B50;&#x9677;&#x9631;&#x7CFB;&#x7EDF;&#x6765;&#x6807;&#x8BC6;&#x529F;&#x80FD; cag PAI &#x5BA3;&#x4F20;&#x5458;&#x3002;&#x7ED3;&#x679C;&#x8868;&#x660E; H.pyloricag &#x6392;&#x4E0A;&#x57FA;&#x56E0;&#x8868;&#x8FBE;&#x7684;&#x53D8;&#x5316;&#x8FD1; 5 &#x4E2A;&#x6570;&#x91CF;&#x7EA7;&#x548C;&#x7EC4;&#x7EC7; cag PAI &#x57FA;&#x56E0;&#x8F6C;&#x5F55;&#x5355;&#x4F4D;&#x6210;&#x5B88;&#x6052;&#x51E0;&#x4E2A; H.&#x87BA;&#x6746;&#x83CC;&#x83CC;&#x682A;&#xFF0C;&#x5305;&#x62EC; 26695&#xFF0C;J99&#x3001; G27 &#x548C; J166 &#x4E4B;&#x95F4;&#x3002;&#x6211;&#x4EEC;&#x53D1;&#x73B0; 20 &#x6210;&#x7EE9;&#x5355;&#x5185; cag &#x6392;&#x5934;&#xFF0C;&#x5176;&#x4E2D;&#x8BB8;&#x591A;&#x53EF;&#x80FD;&#x91CD;&#x53E0;&#x7684;&#x8BC1;&#x636E;&#x3002;&#x6211;&#x4EEC;&#x7684;&#x6570;&#x636E;&#x8868;&#x660E;&#x81F3;&#x5C11; 11 operons&#xFF1A; cag1 4&#x3001; cag3 4&#x3001; cag10-9&#x3001; cag8 7&#x3001; cag6-5&#x3001; cag11-12&#x3001; cag16-17&#x3001; cag19-18&#x3001; cag21-20&#x3001; cag23-22 &#x548C; cag25-24 &#x4EE5;&#x53CA;&#x4E94;&#x4E2A; monocistronic &#x57FA;&#x56E0; (cag4&#x3001; cag13&#x3001; cag14&#x3001; cag15&#x3001; cag26)&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x56DB;&#x6211;&#x4EEC;&#x529F;&#x80FD;&#x786E;&#x5B9A;&#x542F;&#x52A8;&#x5B50;&#x7684;&#x4F4D;&#x7F6E;&#x8868;&#x660E;&#x4ED6;&#x4EEC;&#x5BFC;&#x6F14;&#x8868;&#x8FBE;&#x7684;&#x5728;&#x4E00;&#x4E2A;&#x6848;&#x4F8B;&#x4E2D;&#xFF0C;&#x622A;&#x65AD;&#x7248;&#x672C;&#x7684; cag26 &#x548C;&#x5728;&#x5176;&#x4ED6;&#x4E09;&#x4E2A;&#xFF0C;&#x804A;&#x5929;&#x8BB0;&#x5F55;&#xFF0C;&#x662F;&#x53CD;&#x4E49; cag7&#xFF0C;cag17&#xFF0C;&#x548C; cag23&#x3002;&#x6211;&#x4EEC;&#x9006;&#x8F6C;&#x5F55;-&#x805A;&#x5408;&#x9176;&#x94FE;&#x53CD;&#x5E94;&#x9A8C;&#x8BC1;&#x8FD9;&#x4E9B;&#x53CD;&#x4E49;&#x5230; cag17 &#x548C; cag23&#xFF0C;&#x8FD9;&#x4E9B;&#x53CD;&#x4E49;&#x7684;&#x8A8A;&#x672C;&#xFF0C;&#x4E24;&#x4E2A;&#x8868;&#x8FBE;&#x5F0F;&#x3002;&#x4E24;&#x8005;&#x5408;&#x8BA1;&#xFF0C;&#x6211;&#x4EEC;&#x7684;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#x8868;&#x660E; cag PAI &#x8F6C;&#x5F55;&#x914D;&#x7F6E;&#x6587;&#x4EF6;&#x4E00;&#x822C;&#x4FDD;&#x5B88;&#x7684;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x83CC;&#x682A;&#xFF0C;26695&#xFF0C;J99&#x3001; G27 &#x548C; J166&#xFF0C;&#x548C;&#x53EF;&#x80FD;&#x7684;&#x590D;&#x6742;&#x3002;

Cag &#x81F4;&#x75C5;&#x5C9B;&#x4E4B;&#x95F4;&#x5E7D;&#x95E8;&#x87BA;&#x6746;&#x83CC;&#x7684;&#x5B88;&#x6052;&#x8F6C;&#x5F55;&#x5355;&#x4F4D;&#x7EC4;&#x7EC7;&#x3002;

The Helicobacter pyloricag pathogenicity island (cag PAI) encodes a type IV secretion system that is more commonly found in strains isolated from patients with gastroduodenal disease than from those with asymptomatic gastritis. Genome-wide organization of the transcriptional units in H. pylori strain 26695 was recently established using RNA sequence analysis (Sharma et al., 2010). Here we used quantitative reverse-transcription polymerase chain reaction of open reading frames and intergenic regions to identify putative cag PAI operons in H. pylori; these operons were analyzed further by transcript profiling after deletion of selected promoter regions. Additionally, we used a promoter-trap system to identify functional cag PAI promoters. The results demonstrated that expression of genes on the H. pyloricag PAI varies by nearly five orders of magnitude and that the organization of cag PAI genes into transcriptional units is conserved among several H. pylori strains, including, 26695, J99, G27, and J166. We found evidence for 20 transcripts within the cag PAI, many of which likely overlap. Our data suggests that there are at least 11 operons: cag1-4, cag3-4, cag10-9, cag8-7, cag6-5, cag11-12, cag16-17, cag19-18, cag21-20, cag23-22, and cag25-24, as well as five monocistronic genes (cag4, cag13, cag14, cag15, and cag26). Additionally, the location of four of our functionally identified promoters suggests they are directing expression of, in one case, a truncated version of cag26 and in the other three, transcripts that are antisense to cag7, cag17, and cag23. We verified expression of two of these antisense transcripts, those antisense to cag17 and cag23, by reverse-transcription polymerase chain reaction. Taken together, our results suggest that the cag PAI transcriptional profile is generally conserved among H. pylori strains, 26695, J99, G27, and J166, and is likely complex.

Conserved Transcriptional Unit Organization of the Cag Pathogenicity Island among Helicobacter pylori Strains.

L&#39;&icirc;le de pathog&eacute;nicit&eacute; Helicobacter pyloricag (cag PAI) encode un syst&egrave;me de s&eacute;cr&eacute;tion de type IV que l&#39;on trouve commun&eacute;ment dans les souches isol&eacute;es de patients atteints de maladie gastroduod&eacute;nale que de ceux atteints de gastrite asymptomatique. Organisation du g&eacute;nome des unit&eacute;s de transcriptionnelles dans la souche de H. pylori 26695 a r&eacute;cemment &eacute;t&eacute; cr&eacute;&eacute;e &agrave; l&#39;aide d&#39;analyse de s&eacute;quence RNA (Sharma et al., 2010). Ici, nous avons utilis&eacute; quantitative reverse transcription polymerase chain reaction des cadres ouverts de lecture et des r&eacute;gions interg&eacute;niques pour identifier les op&eacute;rons PAI cag putatif &agrave; Helicobacter pylori ; ces op&eacute;rons ont &eacute;t&eacute; analys&eacute;s par transcription profilage apr&egrave;s suppression des r&eacute;gions promotrices s&eacute;lectionn&eacute;s. En outre, nous avons utilis&eacute; un syst&egrave;me de siphon-promoteur pour identifier les promoteurs PAI cag fonctionnelle. Les r&eacute;sultats ont d&eacute;montr&eacute; que l&#39;expression de g&egrave;nes sur le pyloricag de H. PAI varie de pr&egrave;s de cinq ordres de grandeur, et que l&#39;Organisation des g&egrave;nes PAI de cag dans des unit&eacute;s de transcriptionnelles est conserv&eacute;e parmi plusieurs souches de H. pylori, y compris, 26695, J99 G27 et J166. Nous avons trouv&eacute; des preuves pour 20 transcriptions au sein de l&#39;ACG PAI, dont beaucoup se chevauchent sans doute. Nos donn&eacute;es sugg&egrave;rent qu&#39;il y a au moins 11 op&eacute;rons : cag1-4, 4-cag3, cag10-9, cag8-7, cag6-5, cag11-12, cag16-17, cag19-18, cag21-20, cag23-22 et cag25-24, ainsi que cinq g&egrave;nes monocistronique (cag4, cag13, cag14, cag15 et cag26). En outre, l&#39;emplacement de quatre de nos promoteurs fonctionnellement identifi&eacute;s sugg&egrave;re qu&#39;ils dirigent l&#39;expression, dans un cas, une version tronqu&eacute;e de cag26 et dans les autres transcriptions de trois, qui sont antisens, cag7, cag17 et cag23. Nous avons v&eacute;rifi&eacute; l&#39;expression de deux de ces transcriptions, ces antisens &agrave; cag17 et cag23, par reverse transcription polymerase chain reaction. Ensemble, nos r&eacute;sultats sugg&egrave;rent que le profil transcriptionnel de cag PAI est g&eacute;n&eacute;ralement conserv&eacute; entre Helicobacter pylori souches, 26695, J99 G27 et J166, et est probablement complexe.

Organisation unit&eacute; conserv&eacute;e transcriptionnelle de l&#39;&icirc;le de pathog&eacute;nicit&eacute; Cag entre Helicobacter pylori souches.

Helicobacter Pyloricag Pathogenit&auml;t Insel (Cag PAI) kodiert f&uuml;r eine Typ-IV-Sekretionssystem, die h&auml;ufiger in isolierte St&auml;mme von Patienten mit Gastroduodenale Krankheit als von denen mit asymptomatische Gastritis gefunden wird. Genomweiten Organisation der transkriptionelle Einheiten in H. Pylori-Stamm 26695 wurde vor kurzem eingerichtet mit RNS-Sequenz-Analyse (Sharma Et Al., 2010). Hier haben wir quantitative Reverse Transkription Polymerase-Kettenreaktion von offene Lesung Frames und intergenetischer Regionen verwendet, um vermeintliche Cag PAI Operone in H. Pylori zu identifizieren; Diese Operonen wurden analysiert durch Abschrift Profilerstellung nach dem L&ouml;schen der ausgew&auml;hlten Projekttr&auml;ger Regionen weiter. Dar&uuml;ber hinaus haben wir ein Projekttr&auml;ger-Trap-System verwendet, funktionale Cag PAI Promotoren zu identifizieren. Die Resultate zeigten, dass die Expression von Genen auf die H. Pyloricag PAI variiert von fast f&uuml;nf Gr&ouml;&szlig;enordnungen und die Organisation der Cag-PAI-Gene in transkriptionelle Einheiten unter mehreren H. Pylori St&auml;mmen, einschlie&szlig;lich 26695, J99 G27 und J166 konserviert wird. Wir fanden Hinweise darauf, f&uuml;r 20-Transkripte innerhalb der Cag PAI, von die viele wahrscheinlich &uuml;berlappen. Unsere Daten zufolge gibt es mindestens 11 Operone: cag1-4, cag3-4, cag10-9, cag8-7, cag6-5, cag11-12, cag16-17, cag19-18, cag21-20, cag23-22, cag25-24, sowie f&uuml;nf Monocistronic-Gene (cag4, cag13, cag14, cag15 und cag26). Dar&uuml;ber hinaus schl&auml;gt die Position von vier unserer funktionell identifizierten Promotoren, sie sind Ausdruck der, Regie, in einem Fall, eine verk&uuml;rzte Version des cag26 und in die anderen drei, Abschriften, die antisense cag7, cag17 und cag23 sind. Wir &uuml;berpr&uuml;ft Ausdruck von zwei dieser antisense Abschriften, die &quot;Antisense&quot; cag17 und cag23, durch Reverse Transkription Polymerasekettenreaktion. Zusammen genommen, unsere Ergebnisse legen nahe, dass das Cag PAI transkriptionelle Profil unter H. Pylori im allgemeinen erhalten bleibt St&auml;mme, 26695, J99 G27 und J166, und ist wahrscheinlich Komplex.

Konservierte transkriptionelle Einheit Organisation der Cag Pathogenit&auml;t Insel zwischen Helicobacter Pylori St&auml;mme.

L&#39;isola di patogenicit&agrave; di Helicobacter pyloricag (cag PAI) codifica per un sistema di secrezione di IV tipo che si trova pi&ugrave; comunemente nei ceppi isolati da pazienti con malattia gastroduodenale rispetto da quelli con gastrite asintomatica. Genome-wide organizzazione delle unit&agrave; trascrizionale nel ceppo di H. pylori 26695 &egrave; stato recentemente stabilito mediante analisi di sequenza del RNA (Sharma et al., 2010). Qui abbiamo usato quantitativa reverse transcription polymerase chain reaction di open reading frames e regioni intergenic per identificare operoni PAI cag putativo di H. pylori; sono stati analizzati questi operoni ulteriore di trascrizione profilatura dopo la cancellazione delle regioni promoter selezionati. Inoltre, abbiamo utilizzato un sistema di promotore-trappola per identificare promotori PAI cag funzionale. I risultati hanno dimostrato che espressione di geni sulla H. pyloricag PAI varia da quasi cinque ordini di grandezza e che l&#39;organizzazione dei geni PAI cag in unit&agrave; trascrizionale &egrave; conservato tra i diversi ceppi di pylori H., tra cui, 26695, J99, G27 e J166. Abbiamo trovato prove per 20 trascrizioni all&#39;interno del cag PAI, molti dei quali probabilmente si sovrappongono. I nostri dati suggeriscono che ci sono almeno 11 operoni: cag1-4, cag3 4, cag10-9, cag8-7, cag6-5, cag11-12, cag16-17, cag19-18, cag21-20, cag23-22 e 24-cag25, come pure cinque geni monocistronic (cag4, cag13, cag14, cag15 e cag26). Inoltre, la sede di quattro dei nostri promotori funzionalmente individuati suggerisce che si stanno dirigendo espressione di, in un caso, una versione troncata del cag26 e in altre tre, le trascrizioni che sono antisense per cag7, cag17 e cag23. Abbiamo verificato l&#39;espressione di due di queste trascrizioni, quelli antisenso per cag17 e cag23, di reazione a catena della polimerasi inversa-trascrizione. Presi insieme, i nostri risultati suggeriscono che il profilo trascrizionale di cag PAI &egrave; generalmente conservato tra H. pylori ceppi, 26695, J99, G27 e J166, ed &egrave; probabile che complesso.

Conservato organizzazione unit&agrave; trascrizionale dell&#39;isola di patogenicit&agrave; Cag tra ceppi l&#39;Helicobacter pylori.

&#x30D8;&#x30EA;&#x30B3;&#x30D0;&#x30AF;&#x30BF;&#x30FC; &#x30FB; &#x30D4;&#x30ED;&#x30EA; pyloricag &#x75C5;&#x539F;&#x6027;&#x30A2;&#x30A4;&#x30E9;&#x30F3;&#x30C9; (cag PAI&#xFF09; &#x3088;&#x308A;&#x4E00;&#x822C;&#x7684;&#x5206;&#x96E2;&#x682A;&#x306B;&#x304A;&#x3051;&#x308B;&#x7121;&#x75C7;&#x5019;&#x6027;&#x80C3;&#x708E;&#x3068;&#x306E;&#x305D;&#x308C;&#x3089;&#x304B;&#x3089;&#x3088;&#x308A;&#x80C3;&#x5341;&#x4E8C;&#x6307;&#x8178;&#x75BE;&#x60A3;&#x60A3;&#x8005;&#x304B;&#x3089;&#x767A;&#x898B;&#x3055;&#x308C;&#x3001;&#x30BF;&#x30A4;&#x30D7; IV &#x5206;&#x6CCC;&#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x3092;&#x30A8;&#x30F3;&#x30B3;&#x30FC;&#x30C9;&#x3057;&#x307E;&#x3059;&#x3002;H. pylori &#x3072;&#x305A;&#x307F; 26695 &#x306E;&#x8EE2;&#x5199;&#x5358;&#x4F4D;&#x306E;&#x30B2;&#x30CE;&#x30E0;&#x5E83;&#x3044;&#x7D44;&#x7E54;&#x306F;&#x3001;&#x6700;&#x8FD1; RNA &#x30B7;&#x30FC;&#x30B1;&#x30F3;&#x30B9;&#x89E3;&#x6790; (&#x30B7;&#x30E3;&#x30EB;&#x30DE; et al. 2010) &#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x8A2D;&#x7ACB;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F; h. &#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x306E;&#x63A8;&#x5B9A; cag PAI &#x30AA;&#x30DA;&#x30ED;&#x30F3;&#x69CB;&#x6210;&#x907A;&#x4F1D;&#x5B50;&#x3092;&#x8B58;&#x5225;&#x3059;&#x308B;&#x306E;&#x306B;&#x958B;&#x3044;&#x305F;&#x30EA;&#x30FC;&#x30C7;&#x30A3;&#x30F3;&#x30B0; &#x30FB; &#x30D5;&#x30EC;&#x30FC;&#x30E0;&#x304A;&#x3088;&#x3073;&#x907A;&#x4F1D;&#x5B50;&#x9593;&#x9818;&#x57DF;&#x306E;&#x5B9A;&#x91CF;&#x7684;&#x9006;&#x8EE2;&#x5199;&#x30DD;&#x30EA;&#x30E1;&#x30E9;&#x30FC;&#x30BC;&#x9023;&#x9396;&#x53CD;&#x5FDC;&#x3092;&#x4F7F;&#x7528;;&#x3053;&#x308C;&#x3089;&#x306E;&#x30AA;&#x30DA;&#x30ED;&#x30F3;&#x5206;&#x6790;&#x3055;&#x308C;&#x305F;&#x9078;&#x629E;&#x3057;&#x305F;&#x30D7;&#x30ED;&#x30E2;&#x30FC;&#x30BF;&#x30FC;&#x9818;&#x57DF;&#x306E;&#x524A;&#x9664;&#x5F8C;&#x306E;&#x30C8;&#x30E9;&#x30F3; &#x30B9;&#x30AF;&#x30EA;&#x30D7;&#x30C8;&#x306E;&#x30D7;&#x30ED;&#x30D5;&#x30A1;&#x30A4;&#x30EA;&#x30F3;&#x30B0;&#x306B;&#x3088;&#x308A;&#x3055;&#x3089;&#x306B;&#x3002;&#x307E;&#x305F;&#x3001;&#x6A5F;&#x80FD;&#x7684;&#x306A; cag PAI &#x30D7;&#x30ED;&#x30E2;&#x30FC;&#x30BF;&#x30FC;&#x3092;&#x8B58;&#x5225;&#x3059;&#x308B;&#x306E;&#x306B;&#x30D7;&#x30ED;&#x30E2;&#x30FC;&#x30BF;&#x30FC; &#x30C8;&#x30E9;&#x30C3;&#x30D7; &#x30B7;&#x30B9;&#x30C6;&#x30E0;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;H. pyloricag PAI &#x306E;&#x907A;&#x4F1D;&#x5B50;&#x306E;&#x767A;&#x73FE;&#x306F;&#x307B;&#x307C; 5 &#x6841;&#x306B;&#x3088;&#x3063;&#x3066;&#x7570;&#x306A;&#x308A;&#x3001;&#x8EE2;&#x5199;&#x5358;&#x4F4D;&#x306B; cag PAI &#x907A;&#x4F1D;&#x5B50;&#x306E;&#x7D44;&#x7E54;&#x3001;26695&#x3001;J99&#x3001;G27 &#x306F;&#x3001;J166 &#x3092;&#x542B;&#x3080;&#x3001;&#x3044;&#x304F;&#x3064;&#x304B;&#x306E; h. &#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x7CFB;&#x7D71;&#x9593;&#x3067;&#x7BC0;&#x7D04;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x591A;&#x304F;&#x306F;&#x3001;&#x304A;&#x305D;&#x3089;&#x304F;&#x91CD;&#x8907; 20 &#x30C8;&#x30E9;&#x30F3; &#x30B9;&#x30AF;&#x30EA;&#x30D7;&#x30C8; cag PAI&#x3001;&#x5185;&#x306E;&#x8A3C;&#x62E0;&#x3092;&#x767A;&#x898B;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x6211;&#x3005; &#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x5C11;&#x306A;&#x304F;&#x3068;&#x3082; 11 &#x30AA;&#x30DA;&#x30ED;&#x30F3;&#x63D0;&#x6848;&#x3059;&#x308B;: cag1 4&#x3001;cag3 4&#x3001;cag10 9&#x3001;cag8 7&#x3001;cag6 5&#x3001;cag11 12&#x3001;cag16 17&#x3001;cag19 18&#x3001;cag21 20, cag23 22 cag25 24 &#x3068; 5 monocistronic &#x907A;&#x4F1D;&#x5B50; (cag4&#x3001;cag13&#x3001;cag14&#x3001;cag15&#x3001;&#x304A;&#x3088;&#x3073; cag26)&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x79C1;&#x305F;&#x3061;&#x306E;&#x6A5F;&#x80FD;&#x7684;&#x540C;&#x5B9A;&#x3055;&#x308C;&#x305F;&#x30D7;&#x30ED;&#x30E2;&#x30FC;&#x30BF;&#x30FC;&#x306E; 4 &#x3064;&#x306E;&#x5834;&#x6240;&#x3067;&#x306F;&#x3001;&#x5F0F;&#x306E; 1 &#x3064;&#x306E;&#x30B1;&#x30FC;&#x30B9;&#x306F;&#x3001;&#x5207;&#x308A;&#x6368;&#x3066;&#x3089;&#x308C;&#x305F;&#x30D0;&#x30FC;&#x30B8;&#x30E7;&#x30F3;&#x306E; cag26 &#x3068; cag7&#x3001;cag17&#x3001;&#x304A;&#x3088;&#x3073; cag23 &#x306B;&#x30A2;&#x30F3;&#x30C1;&#x30BB;&#x30F3;&#x30B9;&#x306F;&#x4ED6;&#x306E; 3 &#x3064;&#x3001;&#x30C8;&#x30E9;&#x30F3; &#x30B9;&#x30AF;&#x30EA;&#x30D7;&#x30C8;&#x6F14;&#x51FA;&#x3057;&#x3066;&#x304A;&#x308A;&#x307E;&#x3059;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x9006;&#x8EE2;&#x5199;&#x30DD;&#x30EA;&#x30E1;&#x30E9;&#x30FC;&#x30BC;&#x9023;&#x9396;&#x53CD;&#x5FDC;&#x306B;&#x3088;&#x3063;&#x3066;&#x5F0F; cag17 &#x3068; cag23&#x3001;&#x305D;&#x308C;&#x3089;&#x306E;&#x30A2;&#x30F3;&#x30C1;&#x30BB;&#x30F3;&#x30B9;&#x3053;&#x308C;&#x3089;&#x30A2;&#x30F3;&#x30C1;&#x30BB;&#x30F3;&#x30B9;&#x8EE2;&#x5199;&#x7523;&#x7269;&#x306E; 2 &#x3064;&#x306E;&#x3053;&#x3068;&#x3092;&#x78BA;&#x8A8D;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x4E00;&#x7DD2;&#x306B;&#x53D6;&#x3089;&#x308C;&#x3066;&#x3001;cag PAI &#x8EE2;&#x5199;&#x30D7;&#x30ED;&#x30D5;&#x30A1;&#x30A4;&#x30EB;&#x304C;&#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x306E;&#x9593;&#x3067;&#x4E00;&#x822C;&#x7684;&#x306B;&#x7BC0;&#x7D04;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x793A;&#x5506;&#x7CFB;&#x7D71;&#x3001;26695&#x3001;J99&#x3001;G27 &#x306F;&#x3001;J166&#x3001;&#x304A;&#x3088;&#x3073;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x8907;&#x96D1;&#x3067;&#x3059;&#x3002;

&#x4FDD;&#x5B58;&#x3055;&#x308C;&#x305F;&#x8EE2;&#x5199;&#x5358;&#x4F4D;&#x7D44;&#x7E54; Cag &#x75C5;&#x539F;&#x6027;&#x30A2;&#x30A4;&#x30E9;&#x30F3;&#x30C9; &#x30D4;&#x30ED;&#x30EA;&#x83CC;&#x83CC;&#x682A;&#x306E;&#x9593;&#x3067;&#x3002;

&#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; pyloricag pathogenicity &#xC12C; (cag &#xD30C;&#xC774;) &#xB354; &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xBB34; &#xC99D;&#xC0C1; &#xC704; &#xC5FC;&#xACFC; &#xADF8; &#xBCF4;&#xB2E4; gastroduodenal &#xC9C8;&#xBCD1;&#xC744; &#xAC00;&#xC9C4; &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xBD84;&#xB9AC; &#xB41C; &#xC885;&#xC790;&#xC5D0;&#xC11C; &#xBC1C;&#xACAC; &#xD615;&#xC2DD; IV &#xBD84; &#xBE44; &#xC2DC;&#xC2A4;&#xD15C;&#xC744; &#xC778;&#xCF54;&#xB529;&#xD569;&#xB2C8;&#xB2E4;. H. pylori &#xC2A4;&#xD2B8;&#xB808;&#xC778; 26695 transcriptional &#xB2E8;&#xC704;&#xC758; &#xAC8C;&#xB188; &#xB113;&#xC740; &#xC870;&#xC9C1; &#xCD5C;&#xADFC; RNA &#xC2DC;&#xD000;&#xC2A4; &#xBD84;&#xC11D; (Sharma &#xC678;., 2010)&#xB97C; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xC124;&#xB9BD; &#xB418;&#xC5C8;&#xB2E4;. &#xC5EC;&#xAE30;&#xC5D0;&#xC11C; &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xD30C;&#xC77C;&#xB85C;&#xB9AC;; &#xC0C1; cag &#xD30C;&#xC774; operons &#xC2DD;&#xBCC4; &#xD558; &#xC5F4;&#xB824;&#xC788;&#xB294; &#xB3C5;&#xC11C; &#xD504;&#xB808;&#xC784; &#xBC0F; intergenic &#xC9C0;&#xC5ED;&#xC758; &#xC591;&#xC801; &#xC5ED; &#xC804;&#xC0AC; &#xD6A8;&#xC18C; &#xC5F0;&#xC1C4; &#xBC18;&#xC751;&#xC744; &#xC0AC;&#xC6A9; &#xC774; operons &#xBD84;&#xC11D; &#xD588;&#xB2E4; &#xC0AC;&#xBCF8; &#xC0AD;&#xC81C; &#xC120;&#xD0DD;&#xD55C; &#xBC1C;&#xAE30;&#xC778; &#xC9C0;&#xAD6C;&#xC758; &#xD504;&#xB85C; &#xD30C;&#xC77C;&#xB9C1; &#xD558; &#xC5EC; &#xC790;&#xC138;&#xD55C;. &#xB610;&#xD55C;, &#xBC1C;&#xAE30;&#xC778; &#xD2B8;&#xB7A9; &#xC2DC;&#xC2A4;&#xD15C; &#xC0AC;&#xC6A9; &#xD558;&#xB294; &#xC2DD;&#xBCC4; &#xAE30;&#xB2A5; cag &#xD30C;&#xC774; &#xBC1C;&#xAE30;&#xC778;. &#xACB0;&#xACFC; &#xC2DC;&#xC5F0; H. pyloricag &#xD30C;&#xC774;&#xC5D0; &#xC720;&#xC804;&#xC790;&#xC758; &#xD45C;&#xC815;&#xC744; &#xAC70;&#xC758; 5 &#xC99D;&#xAC00;&#xD560; &#xB2E4;&#xB974;&#xBA70; transcriptional &#xB2E8;&#xC704;&#xB85C; cag &#xD30C;&#xC774; &#xC720;&#xC804;&#xC790; &#xC870;&#xC9C1; 26695, j99&#xACFC; G27, j166&#xB97C; &#xD3EC;&#xD568; &#xD55C; &#xC5EC;&#xB7EC; H. &#xD30C;&#xC77C;&#xB85C;&#xB9AC; &#xC885;&#xC790; &#xC911;&#xC5D0;&#xC11C; &#xBCF4;&#xC874;. &#xC6B0;&#xB9AC;&#xB294; &#xB9CE;&#xC740; &#xAC00;&#xB2A5;&#xC131;&#xC774; &#xACB9;&#xCE58;&#xB294; cag &#xD30C;&#xC774;, &#xC774;&#xB0B4; 20 &#xC131;&#xC801; &#xC99D;&#xBA85;&#xC11C;&#xC5D0; &#xB300; &#xD55C; &#xC99D;&#xAC70;&#xB97C; &#xBC1C;&#xACAC;. &#xC6B0;&#xB9AC;&#xC758; &#xB370;&#xC774;&#xD130; &#xC801;&#xC5B4;&#xB3C4; 11 operons &#xC81C;&#xC548;: cag1 4, cag3 4, cag10-9, cag8-7, cag6-5, cag11 12, cag16-17, cag19-18, cag21-20, cag23-22, &#xBC0F; cag25 24&#xB85C; 5 &#xAC1C;&#xC758; monocistronic &#xC720;&#xC804;&#xC790; (cag4, cag13, cag14, cag15, &#xBC0F; cag26). &#xB610;&#xD55C;, 4 &#xC6B0;&#xB9AC;&#xC758; &#xAE30;&#xB2A5;&#xC801;&#xC73C;&#xB85C; &#xD655;&#xC778; &#xB41C; &#xBC1C;&#xAE30;&#xC778; &#xC704;&#xCE58; &#xD55C; &#xACBD;&#xC6B0; cag26 &#xBC0F; cag7, cag17, &#xBC0F; cag23 &#xC13C;&#xC2A4;&#xB294; &#xB2E4;&#xB978; &#xC138; &#xAC00;&#xC9C0;, &#xC131;&#xC801;&#xD45C;&#xC5D0; &#xC798;&#xB9B0;&#xB41C; &#xBC84;&#xC804; &#xD45C;&#xD604;, &#xC9C0;&#xC2DC;&#xB294; &#xADF8;&#xB4E4;&#xC740; &#xC81C;&#xC548; &#xD569;&#xB2C8;&#xB2E4;. &#xC2DD; &#xB450; &#xC774;&#xB7EC;&#xD55C; &#xC13C;&#xC2A4; &#xC131;&#xC801;&#xD45C;&#xC758; cag17&#xC640; cag23, &#xADF8; antisense &#xC5ED; &#xC804;&#xC0AC; &#xD6A8;&#xC18C; &#xC5F0;&#xC1C4; &#xBC18;&#xC751;&#xC5D0; &#xC758;&#xD574; &#xD655;&#xC778;&#xD569;&#xB2C8;&#xB2E4;. &#xD568;&#xAED8; &#xCC0D;&#xC740;, &#xC6B0;&#xB9AC;&#xC758; &#xACB0;&#xACFC; &#xC81C;&#xC548; cag &#xD30C;&#xC774; transcriptional &#xD504;&#xB85C;&#xD544; &#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xC911; &#xBCF4;&#xC874; &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xC885;&#xC790;, 26695, j99&#xACFC; G27, J166, &#xADF8;&#xB9AC;&#xACE0; &#xAC00;&#xB2A5;&#xC131;&#xC774; &#xBCF5;&#xC7A1;.

&#xD5EC;&#xB9AC;&#xCF54;&#xBC15;&#xD130; &#xD30C;&#xC77C;&#xB85C;&#xB9AC; &#xAE34;&#xC7A5; &#xAC00;&#xC6B4;&#xB370; Cag Pathogenicity &#xC12C;&#xC758; &#xBCF4;&#xC874;&#xB41C; Transcriptional &#xB2E8;&#xC704; &#xC870;&#xC9C1;.

La isla de patogenicidad de Helicobacter pyloricag (cag PAI) codifica un sistema de secreci&oacute;n tipo IV que se encuentra m&aacute;s com&uacute;nmente en cepas aisladas de pacientes con enfermedad gastroduodenal que de aquellos con gastritis asintom&aacute;tica. Organizaci&oacute;n del genoma de las unidades transcripcionales en cepa de H. pylori 26695 se estableci&oacute; recientemente mediante el an&aacute;lisis de la secuencia de ARN (Sharma et al., 2010). Aqu&iacute; utilizamos la reacci&oacute;n en cadena de polimerasa cuantitativa de reverso-transcripci&oacute;n de marcos de lectura abierta y regiones interg&eacute;nicas identificar supuestos cag operones PAI en H. pylori; se analizaron estos operones otra transcripci&oacute;n perfilando despu&eacute;s de eliminaci&oacute;n de regiones promotoras seleccionadas. Adem&aacute;s, utilizamos un sistema promotor-trampa para identificar promotores PAI de cag funcional. Los resultados demostraron que la expresi&oacute;n de genes en el H. pyloricag PAI var&iacute;a en casi cinco &oacute;rdenes de magnitud y que la organizaci&oacute;n de genes de cag PAI en unidades transcripcionales se conserva entre varias cepas de pylori H., incluyendo, 26695, J99, G27 y J166. Se encontraron pruebas para 20 transcripciones en el cag PAI, muchos de los cuales probablemente se superponen. Nuestros datos sugieren que hay al menos 11 operones: cag1-4, cag3-4, cag10-9, cag8-7, cag6-5, cag11-12, cag16-17, cag19-18, cag21-20, cag23-22 y cag25-24, as&iacute; como cinco genes monocistronic (cag4, cag13, cag14, cag15 y cag26). Adem&aacute;s, la localizaci&oacute;n de cuatro de nuestros promotores funcionalmente identificadas sugiere que dirige expresi&oacute;n de, en un caso, una versi&oacute;n truncada de cag26 y en los otros tres, transcritos que son antisentidos para cag7, cag17 y cag23. Comprobamos la expresi&oacute;n de dos de estas transcripciones antisentidas, &eacute;sos antisentido para cag17 y cag23, por reacci&oacute;n en cadena de polimerasa de la reverso-transcripci&oacute;n. Tomados en conjunto, nuestros resultados sugieren que el perfil transcripcional de cag PAI generalmente se conserva entre h.pylori cepas, 26695, J99, G27 y J166, y es probable que complejo.

Organizaci&oacute;n de unidad transcripcional conservados de la isla de patogenicidad Cag entre cepas del Helicobacter pylori.

Selective C-F bond activation: substitution of unactivated alkyl fluorides using YbI₃.

Imidazolium-based ionic liquids (ILs) serve both as recyclable reaction media and as precatalysts for the N-heterocyclic carbene-catalyzed conjugate addition of α,β-unsaturated aldehydes to chalcones. The reaction produces a broad scope of 1,6-ketoesters incorporating an anti-diphenyl moiety in high yields and with high stereoselectivity. In recycling experiments, the IL can be reused up to five times with retained reactivity and selectivity. Moreover, the 1,6-ketoesters form self-assembled organogels in aliphatic hydrocarbons. The reaction protocol is robust, easily operated, scalable and highly functionalized compounds can be obtained from inexpensive and readily accessible starting materials.

Linda Ta

Chemistry and Chemical Engineering

Chalmers University of Technology

Highly Stereoselective Synthesis of 1,6-Ketoesters Mediated by Ionic Liquids: A Three-component Reaction Enabling Rapid Access to a New Class of Low Molecular Weight Gelators