TROD: T7 RNAi Oligo Designer

We have developed T7 RNAi Oligo Designer (TROD), a web application for RNA interference studies. TROD greatly facilitates the design of oligodeoxynucleotide sequences for the in vitro production of siRNA duplexes with T7 RNA polymerase. Given a query cDNA sequence, the program scans for appropriate target sequences based on the constraints of the T7 RNA polymerase method and published criteria for RNA interference with siRNAs. The output is an ordered and prioritized list of ready-to-order DNA oligonucleotide sequences, with links to perform a BLAST search to ascertain target sequence specificity. The TROD web service is available at http://www.cellbio.unige.ch/RNAi.htm

Peter Fauser / Jürgen John / Rüdiger Stutz (Hrsg.): Peter Petersen und die Jenaplan-Pädagogik, Historische und aktuelle Perspektiven unter Mitwirkung von Christian Faludi, Stuttgart: Franz Steiner Verlag 2012 [Rezension]

Rezension von: Peter Fauser / Jürgen John / Rüdiger Stutz (Hrsg.): Peter Petersen und die Jenaplan-Pädagogik, Historische und aktuelle Perspektiven, unter Mitwirkung von Christian Faludi, Stuttgart: Franz Steiner Verlag 2012 (512 S.; ISBN 978-3-515-10208-7; 75,00 EUR

Max Liedtke / Horant Schulz: Knabenchor – Last, Glück, Lebenschance? Eine Untersuchung am Beispiel des Windsbacher Knabenchors. Augsburg: Wißner-Verlag 2012 [Rezension]

Rezension von: Max Liedtke / Horant Schulz: Knabenchor – Last, Glück, Lebenschance? Eine Untersuchung am Beispiel des Windsbacher Knabenchors, Augsburg: Wißner-Verlag 2012 (156 S.; ISBN 978-3-89639-845-1

Engels und das Problem der Naturdialektik: Versuch einer kritischen Reflexion

Seit ihren ersten Anfängen bereitete der marxistischen Bewegung das Problem der Naturwissenschaften, ihrer Denkform, ihres absoluten Wahrheits- und Objektivitätsanspruches - aus ihren formalen, scheinbar ahistorisch und Allgemeingültigkeit reklamierdenden Methoden und Resultaten abgeleitet - etliche Bauchschmerzen. Von diesen Bauchschmerzen werden aktuell und wohl noch in näherer Zukunft all jene Genossen befallen werden, die in naturwissenschaftlich-technischen Bereichen - an Hochschulen, TH's oder den Arbeitsbereichen der technisch-wissenschaftlichen Intelligenz - sich an der Kritik der „bürgerlichen Naturwissenschaften" versuchen, aus dieser ihre praktische Politik bestimmen resp. diese Kritik selbst ins Zentrum ihrer Politik stellen. Denn auf einer ersten Ebene erweist sich das, was kritisiert werden soll, als augenscheinlich funktionstüchtig und erfolgreich; dagegen muß das, was kritikfest sein könnte, seine Funktionsfähigkeit noch unter Beweis stellen

On globally sparse Ramsey graphs

We say that a graph $G$ has the Ramsey property w.r.t.\ some graph $F$ and some integer $r\geq 2$, or $G$ is $(F,r)$-Ramsey for short, if any $r$-coloring of the edges of $G$ contains a monochromatic copy of $F$. R{\"o}dl and Ruci{\'n}ski asked how globally sparse $(F,r)$-Ramsey graphs $G$ can possibly be, where the density of $G$ is measured by the subgraph $H\subseteq G$ with the highest average degree. So far, this so-called Ramsey density is known only for cliques and some trivial graphs $F$. In this work we determine the Ramsey density up to some small error terms for several cases when $F$ is a complete bipartite graph, a cycle or a path, and $r\geq 2$ colors are available

Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5'-terminal mRNA cap structure (m7GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N7-substituent of m7GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N'-(2-methyl-propyl)-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m7GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5'-deoxy-5'-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N7-methyl-guanosine (4a), N7-3-chlorobenzyl-5'-deoxy-5'-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guanosine (4f), and N7-benzyl-5'-deoxy-5'-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents

Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5'-terminal mRNA cap structure (m7GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N7-substituent of m7GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N'-(2-methyl-propyl)-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m7GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5'-deoxy-5'-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N7-methyl-guanosine (4a), N7-3-chlorobenzyl-5'-deoxy-5'-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guanosine (4f), and N7-benzyl-5'-deoxy-5'-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents

A J-protein is an essential subunit of the presequence translocase–associated protein import motor of mitochondria

Transport of preproteins into the mitochondrial matrix is mediated by the presequence translocase–associated motor (PAM). Three essential subunits of the motor are known: mitochondrial Hsp70 (mtHsp70); the peripheral membrane protein Tim44; and the nucleotide exchange factor Mge1. We have identified the fourth essential subunit of the PAM, an essential inner membrane protein of 18 kD with a J-domain that stimulates the ATPase activity of mtHsp70. The novel J-protein (encoded by PAM18/YLR008c/TIM14) is required for the interaction of mtHsp70 with Tim44 and protein translocation into the matrix. We conclude that the reaction cycle of the PAM of mitochondria involves an essential J-protein