Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides-1

Rrows point to the position of the successfully exchanged nucleotides. The upper base code shows the sequence of the analyzed clones, the lower base code the original sequence of the transfected V79-151 cells.<p><b>Copyright information:</b></p><p>Taken from "Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides"</p><p>http://www.biomedcentral.com/1471-2199/9/14</p><p>BMC Molecular Biology 2008;9():14-14.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2266939.</p><p></p

Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides-6

Rrows point to the position of the successfully exchanged nucleotides. The upper base code shows the sequence of the analyzed clones, the lower base code the original sequence of the transfected V79-151 cells.<p><b>Copyright information:</b></p><p>Taken from "Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides"</p><p>http://www.biomedcentral.com/1471-2199/9/14</p><p>BMC Molecular Biology 2008;9():14-14.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2266939.</p><p></p

Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides-0

E) ore 151 (dark blue) respectively. The possible positions for the second (silent) exchange are given in red. (B) Structure of the oligonucleotides showing the first mismatch at position 153 and the second mismatch at position 147 in various distance from the unmodified 3'-end. (C) Structure of the oligonucleotides with different length, modified with PTO and showing the first mismatch at position 151 and the second mismatch at position 159.<p><b>Copyright information:</b></p><p>Taken from "Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides"</p><p>http://www.biomedcentral.com/1471-2199/9/14</p><p>BMC Molecular Biology 2008;9():14-14.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2266939.</p><p></p

Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides-4

Is indicates the distance of the second mismatch (independent of its position in upstream or downstream direction) from the first exchange position. ● first mismatch at position 151, modified by TA-clamps. ◀ : first mismatch at position 153, modified by TA-clamps. ■ : first mismatch at position 151, modified by PTO. The black line shows the linear fit of the data points from the experiments with the three different kinds of oligonucleotides.<p><b>Copyright information:</b></p><p>Taken from "Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides"</p><p>http://www.biomedcentral.com/1471-2199/9/14</p><p>BMC Molecular Biology 2008;9():14-14.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2266939.</p><p></p

Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides-5

E) ore 151 (dark blue) respectively. The possible positions for the second (silent) exchange are given in red. (B) Structure of the oligonucleotides showing the first mismatch at position 153 and the second mismatch at position 147 in various distance from the unmodified 3'-end. (C) Structure of the oligonucleotides with different length, modified with PTO and showing the first mismatch at position 151 and the second mismatch at position 159.<p><b>Copyright information:</b></p><p>Taken from "Simultaneous targeted exchange of two nucleotides by single-stranded oligonucleotides clusters within a region of about fourteen nucleotides"</p><p>http://www.biomedcentral.com/1471-2199/9/14</p><p>BMC Molecular Biology 2008;9():14-14.</p><p>Published online 28 Jan 2008</p><p>PMCID:PMC2266939.</p><p></p

Le livre dans le livre: la représentation du livre, de la lecture et du lecteur au cœur des albums

Le livre dans le livre... Une exploration rapide de la littérature enfantine contemporaine montre que le livre est souvent représenté dans bon nombre d’albums destinés aux enfants de maternelle ou de primaire. Si l’objet-livre apparait régulièrement au détour d’une page, il arrive en outre que l’album mette en scène le lecteur et l’acte de lecture, voire renouvelle l’acte de lecture. Dès lors, la présente contribution se propose dans un premier temps de dresser une recension des albums donnant à voir des livres, des lectures et des lecteurs. Si nous ne pourrons bien évidemment prétendre à l’exhaustivité, nous nous appuyons sur un important corpus de référence. La visée est de fournir une typologie précise des phénomènes identifiés. Dans un second temps, nous tenterons de montrer les implications didactiques de notre inventaire et de notre analyse. Ainsi, en quoi l’usage d’albums mettant en scène des livres peut-il avoir une incidence, et laquelle ?, chez les élèves du primaire sur leur rapport à la lecture, leur posture de lecteur, leur conception des fonctions du livre ou leur représentation de l’objet-livre

TRAIL-Induced Apoptosis Is Preferentially Mediated via TRAIL Receptor 1 in Pancreatic Carcinoma Cells and Profoundly Enhanced by XIAP Inhibitors

Purpose: We previously reported that small molecule X-linked inhibitor of apoptosis (XIAP) inhibitors synergize with soluble TRAIL to trigger apoptosis in pancreatic carcinoma cells. Because cancers may preferentially signal via 1 of the 2 agonistic TRAIL receptors, we investigated these receptors as a therapeutic target in pancreatic cancer in the present study. Experimental Design: We examined TRAIL receptor expression and cytotoxicity of specific monoclonal antibodies to TRAIL-R1 (HGS-ETR1, mapatumumab) or TRAIL-R2 (HGS-ETR2, lexatumumab) and of TRAIL receptor selective mutants alone and in combination with small molecule XIAP inhibitors in pancreatic cancer cell lines, in primary specimens, and in a xenotransplant model in vivo. Results: The majority of primary pancreatic carcinoma samples and all cell lines express one or both agonistic TRAIL receptors. Nine of 13 cell lines are more sensitive to mapatumumab-induced apoptosis, whereas lexatumumab requires cross-linking for maximal activity. Similarly, TRAIL-R1 selective mutants display higher cytotoxicity than TRAIL-R2 selective mutants. Small molecule XIAP inhibitors preferentially act in concert with mapatumumab to trigger caspase activation, caspase-dependent apoptosis, and suppress clonogenic survival. Also, primary cultured pancreatic carcinoma cells are more susceptible to mapatumumab than lexatumumab, which is significantly enhanced by a XIAP inhibitor. Importantly, combined treatment with mapatumumab and a XIAP inhibitor cooperates to suppress tumor growth in vivo. Conclusions: Mapatumumab exerts antitumor activity, especially in combination with XIAP inhibitors against most pancreatic carcinoma cell lines, whereas lexatumumab requires cross-linking for optimal cytotoxicity. These findings have important implications for the design of TRAIL-based protocols for pancreatic cancer. ©2010 AACR