Structure of Arc repressor in solution: evidence for a family of beta-sheet DNA-binding proteins

The Arc repressor, which is involved in the switch between lysis and lysogeny of Salmonella bacteriophage P22, does not belong to any of the known classes of DNA-binding proteins. Mutagenesis studies show that the DNA-binding region is located in the 15 N-terminal amino-acid residues. We have now determined the three-dimensional structure of the Arc dimer from an extensive set of interproton-distance data obtained from 1H NMR spectroscopy. A priori, intra- and inter-monomer nuclear Overhauser effects (NOEs) cannot be distinguished for a symmetric dimer. But by using the homology with the Escherichia coli Met repressor we could interpret the NOEs unambiguously in an iterative structure refinement procedure. The final structure satisfies a large set of NOE constraints (1,352 for the dimer). It shows a strongly intertwined dimer, in which residues 8-14 of different monomers form an antiparallel beta-sheet. A model for the Arc repressor-operator complex can account for all available biochemical and genetic data. In this model two Arc dimers bind with their beta-sheet regions in successive major grooves on one side of the DNA helix, similar to the Met repressor interaction. Thus, Arc and Met repressors are members of the same family of proteins, which contain an antiparallel beta-sheet as the DNA-binding motif.     

Radiation carcinogenesis in experimental animals

Exposure of man to relatively high doses of ionizing radiation is generally restricted to accidental situations, with very limited knowledge about the actual doses received. Animal experiments can be performed under standardized and controlled conditions and can provide information on the dose-response relationships for radiation carcinogenesis. The risk of inducing neoplastic late effects after total-body irradiation with relatively high doses has been demonstrated for larger animals, such as monkeys and dogs. The bone marrow, the mammary glands and the lungs are among the tissues with the highest susceptibility for radiation carcinogenesis. Experimental results on tumour induction in rodents are summarized with emphasis on the effectiveness in dependence on radiation quality and fractionation or dose rate.     

PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans.

PAX6 is widely expressed in the central nervous system. Heterozygous PAX6 mutations in human aniridia cause defects that would seem to be confined to the eye. Magnetic resonance imaging (MRI) and smell testing reveal the absence or hypoplasia of the anterior commissure and reduced olfaction in a large proportion of aniridia cases, which shows that PAX6 haploinsuffiency causes more widespread human neuro developmental anomalies.     

The design of an epistemology for the management discipline which resolves dilemmas among ethical and other imperatives

We outline an epistemology to resolve dilemmas among conflicting imperatives which arise in management situations involving action programs which are “useful” economically and technically but which, at the same time, must satisfy, among others, aesthetic, ethical, and legal requirements. These “situations” occur in problem domains such as management science, environmental management, conservation management (the science devoted to the protection and preservation of our cultural and historical heritage), urban planning, government administration, and the like. Basically, these actions programs are designed to “improve the state of the real world” and take into account the inevitable conflicts and tradeoffs which inhibit maximization of objectives. In the end, the epistemological framework which is proposed leads to the formulation of a methodology to reconcile the economic, scientific, political, legal, ethical, epistemological, and aesthetic imperatives, in the context of a strategic and pragmatic framework.     

Studies on the modulation of the desensitization of the pituitary gland by luteinizing hormone-releasing hormone in the ovariectomized rat

In ovariectomized rats the desensitization of the LH cells in vivo, which develops during constant rate infusion of LHRH, 1) does not depend on a concomitant depletion of the pituitary LH stores, 2) proceeds normally when the hypothalamo-pituitary connection has been severed and 3) is a process in which LH itself is not involved.     

Histologische und zytologische Untersuchungen über das Ependym und seine Abkömmlinge (insbesondere die Epiphyse und den Saccus vasculosus) bei niederen Vertebraten

Summary In the brain wall of different vertebrate species, ependymal cells of different type occur. These cells possess protuberances which protrude into the ventricle.Although cytologically these structures are all variations of one theme, they must at present be interpreted in different ways as regards function.Probably these cell types form a complex system for the regulation of the cerebrospinal fluid. It remains possible that one or more of these cell types act as light receptors.     

Separation of canavanine and canaline by high performance liquid chromatography

The plant amino acid canavanine and its hydrolytic product canaline were successfully separated and identified by Reverse Phase High Performance Liquid Chromatograph (RP-HPLC). This procedure was used to demonstrate the arginase-mediated cleavage of canavanine to yield canaline and urea, and the subsequent formation of a Schiff's base complex between canaline and pyridoxal phosphate. Both aforementioned reactions were demonstrated by RP-HPLC.