Conformational control of bond migration in the D-homo rearrangement of 17-hydroxy-20-keto steroids

The concept of conformational control of bond migration in the trnsition state to theD-homo-annulation of 17-hydroxy-20-keto steroids appears to provide a unified rationale for the observed phenomena.Contribution from Merck & Co., Inc., Rahway, N. J., presented before the North Jersey Section of the American Chemical Society byN. L. Wendler as part of a lecture entitledStereochemical Effects Attending D-Ring Rearrangements in Steroids, February 3, 1959.     

A technique for successful 20 h kidney storage at 4°C

Zusammenfassung Es gelingt die normale Nierenfunktion des 20 h bei 4°C tiefgekühlten Organs durch Perfusion mit Novocain und Reomacrodex von 40°C wieder herzustellen.     

Attempt to induce, in the rat, a hepatitis of cirrhotic origin, using amino steroids: holaphyllaminol or amino 3-beta hydroxy-20-beta pregnene-5]

Holaphyllaminol, or Amino-3 beta-Hydroxy-20-beta Pregnene-5, was administered by gastric tube to male Wistar rats at dose of 50, 100 and 200 mg/kg/24 hr respectively, during 10, 20, 40 and 80 days. This substance provokes hepatic lesions beginning at the periportal region, the characteristics of which are a cholestasis, a canalar proliferation and a fibrosis. The interest of these alterations lies in the fact that they present the same features as certain human chronic hepatitis; their progression, a function of the dose of the toxin and the duration of treatment, may make possible to realisation of a model of experimental chronic hepatitis.     

Uptake of alanine,phenylalanine and tyrosine by L1210 cells at 4°C: Possible effect of lipid solubility

Résumé L'introduction d'un groupe phényl facilite grandement le transfert del-alanine tandis que l'hydroxylation du groupe phényl diminue la facilité de transfert.

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Supported in part by a grant from Charles H. Hood Dairy Foundation. I thank Dr.John J. McCormack, and Dr.A. H. Schein, University of Vermont, for helpful discussions.     

The neuroligin and neurexin families: from structure to function at the synapse

Proper brain connectivity and neuronal transmission rely on the accurate assembly of neurotransmitter receptors, cell adhesion molecules and several other scaffolding and signaling proteins at synapses. Several new exciting findings point to an important role for the neuroligin family of adhesion molecules in synapse development and function. In this review, we summarize current knowledge of the structure of neuroligins and neurexins, their potential binding partners at the synapse. We also discuss their potential involvement in several aspects of synapse development, including induction, specificity and stabilization. The implication of neuroligins in cognitive disorders such as autism and mental retardation is also discussed. Received 6 February 2006; received after revision 17 March 2006; accepted 26 April 2006     

An unwelcome discovery: The pole effect in the electric arc, a threat to early 20th century precision spectrometry

In late 1912, Fritz Goos at the Hamburg Physikalisches Staatslaboratorium discovered a systematic dependency of arc-spectra wavelengths on the length of the electric arc used and on its electric parameters, such as, for instance, the current employed. In early 1913, at Heinrich Kayser's better-equipped physical laboratory in Bonn, Goos was able to confirm these effects using a large concave Rowland grating. He was able to establish that variations of between 3 mm and 10 mm in the length of the arc produced wavelength differences of up to 0.02 Å violet shift and -0.007 Å redshift respectively. Further inquiry also revealed a dependency of the wavelength on the region of the arc selected for spectrometric observation. All these surprising effects were soon collectively named pole effect.As is shown in this paper, the pole effect threatened the validity of the results of the entire research tradition of high-precision spectroscopy which, around 1910, had excelled in establishing several internally coherent systems of wavelength assignments. These wavelength catalogues had been established by spectroscopists such as Heinrich Kayser, Paul Eversheim and their co-workers in Bonn, by August Herman Pfund in Baltimore, and by Charles Fabry and Henri Buisson in Marseille under the aegis of the International Union for Co-Operation in Solar Research. They had all produced locally consistent, homogeneous systems of wavelengths with estimated errors sometimes smaller than 0.001 Å. However, long before 1913, strange non-local inconsistencies had emerged between these systems that were of much greater magnitude than the estimated error. The discovery of the pole effect opened up the possibility that variations in the arc parameters used in the measurements, which the different teams had hitherto not specified, were responsible for the systematic differences, in their respective sets of measurements, coming to up to 0.025 Å.This paper explores the interrelations between local knowledge production, the strategies for the establishment of local coherence, and the ways in which the community of physicists and spectroscopists handled a possible threat to this coherence after 1913. Around 1930, a general agreement was reached about the physical cause of the pole effect, namely Stark effects, caused in turn by intermolecular electric fields of ions in the arc. Much before 1930, however, the community had already succeeded in standardizing the instrumentation used in high-precision spectrometry and had conformed its research practice to such an extent that from 1917 on the pole effect could be routinely circumvented in high-precision spectrometry and interferometry. Thus, experimentation along with its instrumentation, indeed had a life of its own, independent of the many unsuccessful efforts to explain the pole effect theoretically.     

Activated protein C binds directly to Tie2: possible beneficial effects on endothelial barrier function

Activated protein C (APC) is a natural anticoagulant with strong anti-inflammatory, anti-apoptotic, and barrier stabilizing properties. These cytoprotective properties of APC are thought to be exerted through its pathway involving the binding of APC to endothelial protein C receptor and cleavage of protease-activated receptors. In this study, we found that APC enhanced endothelial barrier integrity via a novel pathway, by binding directly to and activating Tie2, a transmembrane endothelial tyrosine kinase receptor. Binding assays demonstrated that APC competed with the only known ligands of Tie2, the angiopoietins (Angs). APC bound directly to Tie2 (Kd ~3 nM), with markedly stronger binding affinity than Ang2. After binding, APC rapidly activated Tie2 to enhance endothelial barrier function as shown by Evan’s blue dye transfer across confluent cell monolayers and in vivo studies. Blocking Tie2 restricted endothelial barrier integrity. This study highlights a novel mechanism by which APC binds directly to Tie2 to enhance endothelial barrier integrity, which helps to explain APC’s protective effects in vascular leakage-related pathologies.     

Selection at the Adh locus inDrosophila melanogaster: Adult survivorship-mortality in response to ethanol

Summary Functionally significant biochemical properties of the naturally occurring electrophoretic variants at the Adh locus (ADH^fast and ADH^Slow) are correlated with the adult flies' ability to utilize and survive in an ethanol environment. The results are consistent with the idea that an environmentally dependent form of balancing selection is responsible, at least in part, for the maintenance of the polymorphism at this locus.Acknowledgment. This work was supported by NSF grant DEB 7815466 to J.M.     

The centenary of W. C. Roentgen's discovery: A look at developments in science,clinical radiologic practice and environmental problems

The editors wish to thank Professor M. Elke for having coordinated this review.     

Fusion polypeptides in gene cloning: Potential problems due to conformational alterations at the junction

Summary Many eukaryotic genes are cloned in bacterial hosts as fusion polypeptides. Prediction of the secondary structures for some common prokaryotic fusion polypeptides shows that many junction sites correspond to important secondary structures. It is suggested that such structures could affect (hinder, etc.) the conformation or drive the folding of the neighboring eukaryotic counterparts. Thus the prokaryotic junction should be better performed, in random coil regions, or short fusion prokaryotic polypeptides should be sued.1 October 1986