Ghibertis Hommage an Brunelleschi. Der Wettbewerb um neue Bronzeportale und die Paradiestüren am Florentiner Baptisterium

Die hinterbliebenen Wettbewerbreliefs für neue Bronzeportale des Florentiner Baptisteriums aus dem Jahr 1401 werden erneut einer Analyse unterzogen unter Berücksichtigung einiger kunsttheoretischer Aspekte Leon Battista Albertis. Dabei fallen Parallelen auf zwischen den Positionen Filippo Brunelleschis und Albertis, die sich grundsätzlich von den Prämissen Lorenzo Ghibertis unterscheiden. Letzterer scheint jedoch das Bronzerelief seines Rivalen nie zu vergessen. An zwei Szenen seiner über 20 Jahre später begonnenen sog. Paradiestür lassen sich direkte Űbernahmen aus der Tafel seines Konkurrenten sowie ein indirekt, kunsttheoretisch verwandter Ansatz in der Darstellungsweise aufzeigen, der für Ghibertis Anerkennung der künstlerischen Ideen und Erfindungen Brunelleschis spricht

Resonance assignments of the microtubule-binding domain of the C. elegans spindle and kinetochore-associated protein 1

During mitosis, kinetochores coordinate the attachment of centromeric DNA to the dynamic plus ends of microtubules, which is hypothesized to pull sister chromatids toward opposing poles of the mitotic spindle. The outer kinetochore Ndc80 complex acts synergistically with the Ska (spindle and kinetochore-associated) complex to harness the energy of depolymerizing microtubules and power chromosome movement. The Ska complex is a hexamer consisting of two copies of the proteins Ska1, Ska2 and Ska3, respectively. The C-terminal domain of the spindle and kinetochore-associated protein 1 (Ska1) is the microtubule-binding domain of the Ska complex. We solved the solution structure of the C. elegans microtubule-binding domain (MTBD) of the protein Ska1 using NMR spectroscopy. Here, we report the resonance assignments of the MTBD of C. elegans Ska1.Austrian Science Fund (project P22170, and the doctoral school ‘‘DK Molecular Enzymology’’ (W901-B05)

Trial by Ambush or Avalanche - The Discovery Debacle

I fell in love with the law in 1946, during my first week in law school. It has been a torrid affair ever since. Ever since has entailed seven years of law practice followed by thirty-two years of law professing, eight of these as a dean. Against this backdrop of fealty, I had occasion recently to encounter the legal process as it presently, honest-to-God, exists. This encounter was not as a lawyer, not as a law professor, not as a consultant, not, that is, as a professional impersonally involved, but as the father of the mother in a child-custody case. It was a client exposure. I came away from the experience not merely angry and disillusioned, but outraged. Why

Voluntary Impartial Review of Labor: Some Reflections

The purpose of this paper is to examine the emerging concept of voluntary impartial review of the decisions of organizational tribunals passing upon internal disputes. Attention will center on the application of this concept to labor unions - the only area in which it has yet been tried

Structural Characterization of Pandoraea pnomenusa B-356 Biphenyl Dioxygenase Reveals Features of Potent Polychlorinated Biphenyl-Degrading Enzymes

The oxidative degradation of biphenyl and polychlorinated biphenyls (PCBs) is initiated in Pandoraea pnomenusa B-356 by biphenyl dioxygenase $(BPDO_{B356})$. $BPDO_{B356}$, a heterohexameric $(αβ)_3$ Rieske oxygenase (RO), catalyzes the insertion of dioxygen with stereo- and regioselectivity at the 2,3-carbons of biphenyl, and can transform a broad spectrum of PCB congeners. Here we present the X-ray crystal structures of $BPDO_{B356}$ with and without its substrate biphenyl 1.6-Å resolution for both structures. In both cases, the Fe(II) has five ligands in a square pyramidal configuration: H233 Nε2, H239 Nε2, D386 Oδ1 and Oδ2, and a single water molecule. Analysis of the active sites of $BPDO_{B356}$ and related ROs revealed structural features that likely contribute to the superior PCB-degrading ability of certain BPDOs. First, the active site cavity readily accommodates biphenyl with minimal conformational rearrangement. Second, M231 was predicted to sterically interfere with binding of some PCBs, and substitution of this residue yielded variants that transform 2,2′-dichlorobiphenyl more effectively. Third, in addition to the volume and shape of the active site, residues at the active site entrance also apparently influence substrate preference. Finally, comparison of the conformation of the active site entrance loop among ROs provides a basis for a structure-based classification consistent with a phylogeny derived from amino acid sequence alignments

Selective Pharmacological Targeting of a DEAD Box RNA Helicase

RNA helicases represent a large family of proteins implicated in many biological processes including ribosome biogenesis, splicing, translation and mRNA degradation. However, these proteins have little substrate specificity, making inhibition of selected helicases a challenging problem. The prototypical DEAD box RNA helicase, eIF4A, works in conjunction with other translation factors to prepare mRNA templates for ribosome recruitment during translation initiation. Herein, we provide insight into the selectivity of a small molecule inhibitor of eIF4A, hippuristanol. This coral-derived natural product binds to amino acids adjacent to, and overlapping with, two conserved motifs present in the carboxy-terminal domain of eIF4A. Mutagenesis of amino acids within this region allowed us to alter the hippuristanol-sensitivity of eIF4A and undertake structure/function studies. Our results provide an understanding into how selective targeting of RNA helicases for pharmacological intervention can be achieved