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Search Results: 1 - 10 of 523 matches for " Adrien Eberlin "
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Lestaurtinib Inhibits Histone Phosphorylation and Androgen-Dependent Gene Expression in Prostate Cancer Cells
Jens K?hler, German Erlenkamp, Adrien Eberlin, Tobias Rumpf, Inna Slynko, Eric Metzger, Roland Schüle, Wolfgang Sippl, Manfred Jung
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034973
Abstract: Background Epigenetics is defined as heritable changes in gene expression that are not based on changes in the DNA sequence. Posttranslational modification of histone proteins is a major mechanism of epigenetic regulation. The kinase PRK1 (protein kinase C related kinase 1, also known as PKN1) phosphorylates histone H3 at threonine 11 and is involved in the regulation of androgen receptor signalling. Thus, it has been identified as a novel drug target but little is known about PRK1 inhibitors and consequences of its inhibition. Methodology/Principal Finding Using a focused library screening approach, we identified the clinical candidate lestaurtinib (also known as CEP-701) as a new inhibitor of PRK1. Based on a generated 3D model of the PRK1 kinase using the homolog PKC-theta (protein kinase c theta) protein as a template, the key interaction of lestaurtinib with PRK1 was analyzed by means of molecular docking studies. Furthermore, the effects on histone H3 threonine phosphorylation and androgen-dependent gene expression was evaluated in prostate cancer cells. Conclusions/Significance Lestaurtinib inhibits PRK1 very potently in vitro and in vivo. Applied to cell culture it inhibits histone H3 threonine phosphorylation and androgen-dependent gene expression, a feature that has not been known yet. Thus our findings have implication both for understanding of the clinical activity of lestaurtinib as well as for future PRK1 inhibitors.
Glutamine-Expanded Ataxin-7 Alters TFTC/STAGA Recruitment and Chromatin Structure Leading to Photoreceptor Dysfunction
Dominique Helmlinger,Sara Hardy,Gretta Abou-Sleymane,Adrien Eberlin,Aaron B. Bowman,Anne Gansmüller,Serge Picaud,Huda Y. Zoghbi,Yvon Trottier,Làszlò Tora,Didier Devys
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0040067
Abstract: Spinocerebellar ataxia type 7 (SCA7) is one of several inherited neurodegenerative disorders caused by a polyglutamine (polyQ) expansion, but it is the only one in which the retina is affected. Increasing evidence suggests that transcriptional alterations contribute to polyQ pathogenesis, although the mechanism is unclear. We previously demonstrated that theSCA7 gene product, ataxin-7 (ATXN7), is a subunit of the GCN5 histone acetyltransferase–containing coactivator complexes TFTC/STAGA. We show here that TFTC/STAGA complexes purified from SCA7 mice have normal TRRAP, GCN5, TAF12, and SPT3 levels and that their histone or nucleosomal acetylation activities are unaffected. However, rod photoreceptors from SCA7 mouse models showed severe chromatin decondensation. In agreement, polyQ-expanded ataxin-7 induced histone H3 hyperacetylation, resulting from an increased recruitment of TFTC/STAGA to specific promoters. Surprisingly, hyperacetylated genes were transcriptionally down-regulated, and expression analysis revealed that nearly all rod-specific genes were affected, leading to visual impairment in SCA7 mice. In conclusion, we describe here a set of events accounting for SCA7 pathogenesis in the retina, in which polyQ-expanded ATXN7 deregulated TFTC/STAGA recruitment to a subset of genes specifically expressed in rod photoreceptors, leading to chromatin alterations and consequent progressive loss of rod photoreceptor function.
Glutamine-Expanded Ataxin-7 Alters TFTC/STAGA Recruitment and Chromatin Structure Leading to Photoreceptor Dysfunction
Dominique Helmlinger,Sara Hardy equal contributor,Gretta Abou-Sleymane equal contributor,Adrien Eberlin,Aaron B Bowman,Anne Gansmüller,Serge Picaud,Huda Y Zoghbi,Yvon Trottier,Làszlò Tora ,Didier Devys
PLOS Biology , 2006, DOI: 10.1371/journal.pbio.0040067
Abstract: Spinocerebellar ataxia type 7 (SCA7) is one of several inherited neurodegenerative disorders caused by a polyglutamine (polyQ) expansion, but it is the only one in which the retina is affected. Increasing evidence suggests that transcriptional alterations contribute to polyQ pathogenesis, although the mechanism is unclear. We previously demonstrated that theSCA7 gene product, ataxin-7 (ATXN7), is a subunit of the GCN5 histone acetyltransferase–containing coactivator complexes TFTC/STAGA. We show here that TFTC/STAGA complexes purified from SCA7 mice have normal TRRAP, GCN5, TAF12, and SPT3 levels and that their histone or nucleosomal acetylation activities are unaffected. However, rod photoreceptors from SCA7 mouse models showed severe chromatin decondensation. In agreement, polyQ-expanded ataxin-7 induced histone H3 hyperacetylation, resulting from an increased recruitment of TFTC/STAGA to specific promoters. Surprisingly, hyperacetylated genes were transcriptionally down-regulated, and expression analysis revealed that nearly all rod-specific genes were affected, leading to visual impairment in SCA7 mice. In conclusion, we describe here a set of events accounting for SCA7 pathogenesis in the retina, in which polyQ-expanded ATXN7 deregulated TFTC/STAGA recruitment to a subset of genes specifically expressed in rod photoreceptors, leading to chromatin alterations and consequent progressive loss of rod photoreceptor function.
Atribui??o absoluta e geral de is?meros constitucionais por espectrometria de massas: o caso das metilpiperidinas
Eberlin, Marcos N.;Benassi, Mario;
Química Nova , 2012, DOI: 10.1590/S0100-40422012000100004
Abstract: an absolute method is described via mass spectrometry (ms) for the structural assignment of isomers within the class of methylpiperidines. the method explores both the unimolecular and bimolecular gas phase behavior of structurally diagnostic fragment ions (sdfi). for the methylpiperidnes, the isomeric 2-methyl, 3-methyl and 4-methyl 2-azabutadienyl cations are found to function as sdfi. these fragment ions are expected to be formed from all members within the class, to be stable and to retain the structural information of the precursor molecule, and to not interconvert into one another. to characterize these sdfi, both the collision induced dissociation (cid) in argon and bimolecular ion/molecule chemistry with ethyl vinyl ether were compared.
Finding the Zen in Motorcycling
Litton, Adrien
International Journal of Motorcycle Studies , 2008,
Abstract:
Les voyages du récit. Culture écrite et expansion européenne à l’époque moderne : le cas de la Compagnie Hollandaise des Indes Orientales
Adrien Delmas
Atelier du Centre de Recherches Historiques , 2011, DOI: 10.4000/acrh.3944
Abstract: composition du juryMonsieur Fran ois Hartog, école des Hautes études en Sciences Sociales, Directeur,Monsieur Romain Bertrand, Fondation Nationale des Sciences Politiques,Monsieur Fran ois-Joseph Ruggiu, Université de Paris IV-Sorbonne,Monsieur Jean-Frédéric Schaub, école des Hautes études en Sciences Sociales,Monsieur Nigel Worden, University of Cape Town.Thèse soutenue le 1er juillet 2010RésuméPour saisir les relations multiples qui se sont nouées entre la culture écrite et l’expansion euro...
L’écriture de l’histoire et la compétition européenne outre-mer au tournant du xviie siècle
Adrien Delmas
Atelier du Centre de Recherches Historiques , 2011, DOI: 10.4000/acrh.3632
Abstract: Au tournant du xviie siècle, l’irruption des navires fran ais, anglais et hollandais sur les trois océans, rompant avec le monopole ibérique sur les Indes orientales et occidentales, s’accompagne d’un déplacement de la notion de découverte. Afin de saisir les enjeux liés à l’appropriation de cette notion par les concurrents européens du Portugal et de l’Espagne, cet article se concentre sur les écrits de l’historien huguenot Henri Lancelot Voisin de La Popelinière (1541-1608) dans lesquels l’idée de découverte devient l’alpha et l’oméga d’une nouvelle écriture de l’histoire, supérieure en tout point, selon La Popelinière, à ce que les historiographes, Anciens ou Modernes, avaient proposé jusqu’alors. Chemin faisant, la notion se dotait également d’enjeux qui dépassaient largement la seule écriture de l’histoire : le récit des découvertes jouerait dorénavant le r le de garant dans la revendication de prises de possessions outre-mer. At the turn of the seventeenth century, the arrival of French, English and Dutch ships on three oceans and the breaking of the Iberian monopoly over the East and West Indies, was accompanied by a shift in the notion discovery. To understand the issues related to the appropriation of the concept by the European rivals of Portugal and Spain, this article focuses on the writings of the Huguenot historian Henry Lancelot Voisin de La Popeliniere (1541-1608). According to him, the idea of "discovery" should become the alpha and omega of a new writing of history, superior in all points from what historians, be they Ancient or Modern, had previously proposed. In the meantime, the notion was endowed with a significance that went far beyond the single issue of historical writing: the narratives of the discoveries would now play the role of guarantor for claiming possessions overseas.
Helen Farish and Feminine Poetic Identity
Adrien GRAFE
E-rea : Revue électronique d’études sur le Monde Anglophone , 2008, DOI: 10.4000/erea.109
Abstract: Helen Farish est à la fois poète et universitaire, spécialisée dans le domaine de la poésie féminine notamment américaine et de l’interface entre celle-ci et la théorie littéraire. Quelles sont ses propres options poétiques et théoriques, telles qu’elles apparaissent dans les poèmes du recueil Intimates (2005) ? Et qu’a-t-elle pu hériter du féminisme poétique, de poètes tels que M. Rukeyser ou K. Clanchy ? Farish établit sa propre identité poétique, celle d’une jeune femme du XXIème siècle en train de faire la double découverte du langage et du monde, explorant en même temps certaines facettes de la sexualité féminine. A l’aide d’éléments tirés de sources aussi diverses épistémologiquement que la tradition romantique, la réflexion sur le sujet de Nancy K. Miller, ou la pensée de Derrida, l’article examine l’ uvre d’un auteur qui a su tirer parti des combats menés par le féminisme pour se doter d’une voix ironique—y compris envers elle-même—pr nant une identité poétique et une identité du genre, lesquelles font la belle part à la souplesse, au caprice et au risque.
Danielewski-Fieseler surfaces
Adrien Dubouloz
Mathematics , 2004,
Abstract: We study a class of normal affine surfaces with additive group actions which contains in particular the Danielewski surfaces in $\ba^{3}$ given by the equations $x^{n}z=P(y)$, where $P$ is a nonconstant polynomial with simple roots. We call them Danielewski-Fieseler Surfaces. We reinterpret a construction of Fieseler \cite{Fie94} to show that these surfaces appear as the total spaces of certain torsors under a line bundle over a curve with an $r$-fold point. We classify Danielewski-Fieseler surfaces through labelled rooted trees attached to such a surface in a canonical way. Finally, we characterize those surfaces which have a trivial Makar-Limanov invariant in terms of the associated trees.
A Kohno-Drinfeld theorem for the monodromy of cyclotomic KZ connections
Adrien Brochier
Mathematics , 2010,
Abstract: We compute explicitly the monodromy representations of "cyclotomic" analogs of the Knizhnik--Zamolodchikov differential system. These are representations of the type B braid group $B_n^1$. We show how the representations of the braid group $B_n$ obtained using quantum groups and universal $R$-matrices may be enhanced to representations of $B_n^1$ using dynamical twists. Then, we show how these "algebraic" representations may be identified with the above "analytic" monodromy representations.
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