Gap junction structures: Analysis of the x-ray diffraction data

Models for the spatial distribution of protein, lipid and water in gap junction structures have been constructed from the results of the analysis of X-ray diffraction data described here and the electron microscope and chemical data presented in the preceding paper (Caspar, D. L. D., D. A. Goodenough, L. Makowski, and W.C. Phillips. 1977. 74:605-628). The continuous intensity distribution on the meridian of the X-ray diffraction pattern was measured, and corrected for the effects of the partially ordered stacking and partial orientation of the junctions in the X-ray specimens. The electron density distribution in the direction perpendicular to the plane of the junction was calculated from the meridional intensity data. Determination of the interference function for the stacking of the junctions improved the accuracy of the electron density profile. The pair-correlation function, which provides information about the packing of junctions in the specimen, was calculated from the interference function. The intensities of the hexagonal lattice reflections on the equator of the X-ray pattern were used in coordination with the electron microscope data to calculate to the two-dimensional electron density projection onto the plane of the membrane. Differences in the structure of the connexons as seen in the meridional profile and equatorial projections were shown to be correlated to changes in lattice constant. The parts of the junction structure which are variable have been distinguished from the invariant parts by comparison of the X-ray data from different specimens. The combination of these results with electron microscope and chemical data provides low resolution three- dimensional representations of the structures of gap junctions.     

A pilot study of the use of placental cord blood samples in monitoring for mutational events

A pilot study exploring the examination of placental cord blood samples for mutant proteins with one-dimensional electrophoretic techniques is described. Although technical advances are such that the techniques employed in this study are now partially superceded, the practical problems encountered in this study would be typical of any monitoring program of this type. No mutations altering electrophoretic mobility among a battery of 51 different locus products were encountered in a total of 277,747 locus tests. When these data are combined with similar data from other studies, the mutation rate for electromorphs becomes 0.34 X 10(-5)/locus/generation.     

Étude expérimentale de l'auto-association des molécules modèles dipeptidiques. II. Association stéréosélective des molécules énantiomères

Modes of aggregation fo alanine-, norvaline- and valine-contaiing dpepetides with the general formula R₁? C₁O₁? N₂H₂? CHR₂? C₂O₂? N₃H₃? R₃ have been studied in CCl₄ solution by using infrared and nuclear magnetic resonance spectroscopies. Solutions of the pure L isomer and of the racemic mixture do not give identical data. At a given concentration, the racemic mixtrue is more aggregated than the pure enantiomer, and the difference, negligible in the case of alanine derivative, increases wiht the bulkiness of the side cahin R₂. The results show that a selective interaction takes place between enantiomeric molecules, resulting ina dimer associating tow inverse configurated C₅ conformers. The stabilizaion of this dimer proceeds from two symmetrical and intermolecular H₃ … O₁ hydrogen bondings.     

Genetic analysis of thirty-three platelet polypeptides detected in two-dimensional polyacrylamide gels.

Two-dimensional gel electrophoresis followed by silver-staining was utilized to visualize platelet polypeptides for genetic analysis. A subset of 33 polypeptides that were most suited for scoring was selected. Families consisting of father-mother-child trios were studied. Thirty-six polypeptides of a total of 1,413 scored in children's gels exhibited the combination of a normal and a variant polypeptide. The observed index of heterozygosity of 2.55% is comparable to our previously reported findings for red cell proteins.     

The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling

Src homology-2 (SH2) domain-containing phosphatases (Shps) are a small, highly conserved subfamily of protein-tyrosine phosphatases, members of which are present in both vertebrates and invertebrates. The mechanism of regulation of Shps by ligand binding is now well understood. Much is also known about the normal signaling pathways regulated by each Shp and the consequences of Shp deficiency. Recent studies have identified mutations in human Shp2 as the cause of the inherited disorder Noonan syndrome. Shp2 mutations might also contribute to the pathogenesis of some leukemias. In addition, Shp2 might be a key virulence determinant for the important human pathogen Helicobacter pylori. Despite these efforts, however, the key targets of each Shp have remained elusive. Identifying these substrates remains a major challenge for future research.     

MDM2: life without p53

The MDM2 protein suppresses the ability of p53 to inhibit cellular proliferation or to induce cell death. This property underlies the oncogenic potential of MDM2, which is overexpressed in various human tumours. However, MDM2 also has p53-independent activities, which we focus on here. Similar to other oncogenes, surveillance pathways might counteract the deleterious effects of deregulated MDM2 expression. These pathways need to be inactivated for MDM2 oncogenic activity, which targets p53 but also other proteins.