A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV. An unaffected family member is mosaic for the mutation

Summary Ehlers-Danlos syndrome type IV, an inherited connective tissue disease, is usually caused by mutations in the gene for type III collagen. Here, we describe a glycine to glutamic acid substitution in a patient with this syndrome. Previous studies had shown that fibroblasts from the patient, his mother and brother secreted a reduced amount of type III collagen and also produced an overmodified form of the protein that was preferentially retained intracellularly. Peptide mapping experiments indicated that the mutation was located within cyanogen bromide peptide 9. This was supported by chemical cleavage analysis and sequencing of cDNA encoding this region. Allele-specific oligonucleotide hybridisation of genomic DNA confirmed that a G to A mutation converted Gly 847 to Glu. The mutation was present in two other affected family members and also in a third, who was clinically unaffected. Further analysis of this unaffected individual revealed reduced mutant:normal ratios in DNA obtained from both blood and hair samples, showing that she was mosaic for the mutation.     

Effect of rad 54 mutation on the ability of Saccharomyces cerevisiae cells to recover from radiation and thermal injury

The diploid cells of Saccharomyces cerevisiae carrying rad 54 homozygous mutation do not exhibit an ability for any considerable "rapid" postirradiation and post-hyperthermic recovery. A pretreatment with high temperature (50 degrees C) increases the radiation response of mutant cells. Survival of cells overheated before gamma-irradiation is increased by keeping them in water for 2-6 h at 28 degrees C, while the corresponding value of survival for cells treated by each of the factors delivered separately remains constant in these conditions.     

Content of iron and copper in the nuclei and induction of pH 9-labile lesions in L5178Y sublines inversely cross-sensitive to H2O2 and x-rays

Cells from the L5178Y murine lymphoma subline LY-R are twice as resistent to killing by ionizing radiation than the subline LY-S. In contrast, LY-R cells are more sensitive to killing by H₂O₂, the effect being more pronounced at 37 °C than 0 °C. Initial DNA damage after H₂O₂ treatment (both temperatures, 5 min) has been estimated by the comet assay (single-cell gel electrophoresis) and fluorescent halo technique. According to both methods, the initial damage is significantly higher in LY-R cells, particularly that inflicted at O °C. Differences between DNA unwinding and rewinding abilities at pH 9 and 6.9 (estimated by the fluorescent halo technique) point to a considerable difference in pH-9-labile damage between the sublines, as observed previously for x-irradiated cells (Kapiszewska et al. 1992). In contrast to findings with x-irradiated cells, however, after H₂O₂ treatment this damage is more extensive in LY-R cells than in LY-S cells. Thus, the initial pH-9-labile damage corresponds to the pattern of sensitivity to H₂O₂ and x-rays. We suggest that this is caused by different proportions of cuprous and ferric ions found in the nuclei of LY sublines and by the different ability of these ions to react with H₂O₂ and water radiolysis products. The copper/iron ratio in the nucleus is 1.31 in LY-R cells and 4.84 in LY-S cells.     

Patterns in the structural homeostasis of cardiomyocytes

Results of quantitative analysis of the ultrastructura organization (UO) of animal (rabbit, rat, dog) and human cardiomyocytes carried out by means of the point method are presented. A number of stereometric constants which provide structural cardiomyocyte homeostasis (SCH) were revealed: the sum total mitochondrial (MT) and myofibril (MF) volume is a constant value- a "cardiomyocytic constant" (Vmt + Vmf=Kcm); the total growth of MT and MF volumes in different functional states is equal to "0" (dVmt + dVmf=0); adaptational MT and MF rearrangement takes place during an interval of 11% of the volume (deltaVmt=deltaVmf=11 percent; the SCH is maintained by the changes of the UO within the limits of the law of "constancy of volume interrelations" (80; 10; 10), according to which 80 percent of the volume falls on Kcm, 10 percent of the remaining organellae and cell inclusions (Vi) and 10 percent on the plasma cell (Vpl). The assumption on a possibility of universality of the stereometric constants is suggested.     

Co-operative response of chemically excitable membrane: I. Formulation: Unified theory of co-operativity

The lattice-model of Changeux, Thiery, Tung & Kittel (1966) was extended in order to examine the co-operative response of chemically excitable membrane and the exact mathematical correspondence to the Ising model was shown. In this model, two conformational states S and R with different affinities for the ligand are assumed to be accessible to each protomer, which is interacting with the nearest-neighbor protomers. The model is applicable to any kind of symmetrically interacting system consisting of oligomers and lattices and is an extension of previously proposed models of allosteric protein. It includes the model of Monod, Wyman, & Changeux (1965) and that of Koshland, Némethy & Filmer (1966) as the extreme cases of the oligomer. By assuming that a state-transition from S to R in a protomer is accompanied by a unit increase in conductance, the characteristics of dose-response curves of chemically excitable membrane are examined. The Hill's coefficient n_H of dose-response curve, the measure of the co-operativity, is shown to be proportional to the square of the mean fluctuation of the state function, the fraction of protomers in R state.     

Plasticity in mammalian skeletal muscle.

While it has been recognized for many years that different limb muscles belonging to the same mammal may have markedly differing contractile characteristics, it is only comparatively recently that it has been demonstrated that these differences depend upon the motor innervation. By appropriately changing the peripheral nerve innervating a mammalian skeletal muscle, it is possible to change dramatically the contractile behaviour of the reinnervated muscle. The manner by which the motor innervation determines the nature of a muscle fibre's contractile machinery is not completely understood, but it appears that the number and pattern of motor nerve impulses reaching the muscle play an important role. The biochemical changes occurring within muscle fibres whose contractile properties have been modified by altered motor innervation include the synthesis of different contractile proteins.     

Low hydration phase properties of phospholipid mixtures

An experimental investigation of the low hydration phase properties of phospholipid mixtures is described. ²H (D₂O) NMR, X-ray diffraction and differential scanning calorimetry have been used to elucidate the phase properties of mixtures of the mixed chain phospholipids palmitoyloleoylphosphatidylcholine (POPC) and palmitoyloleoylphosphatidylethanolamine (POPE). At 10% hydration pure POPE exhibited a H_II phase above 330 K, a fluid lamellar phase below 315 K, and a minimally hydrated crystalline phase below 300 K. For the 1:1 mixture, the samples exhibited only gel or fluid phases between 270 K and 360 K for hydrations in the range 15% to 30%. Below 15% hydration the mixture exhibited two fluid phases with different repeat spacings, as predicted previously.     

A pulsed NMR study of lipids,bound water and sodium ions in macroscopically-oriented lecithin/water lyotropic liquid crystal model membrane systems

The temperature and orientation dependence of pulsed NMR ‘free induction decay’ signals have been studied in detail for lipid bilayers macroscopically-oriented between glass slides. Results for the lipid molecules (¹H, ³¹P), bound water (²H₂O) and ions dissolved in the aqueous phase (²³Na) are presented. Bilayers of egg-lecithin, dimyristoyl lecithin and potassium oleate have been investigated. In the liquid crystal phase all the signals, including those from bound water and ions exhibit a |3 cos²? ? 1| dependence on orientation of the bilayer normal to the magnetic field. In the case of DML samples, some orientation dependence of both ¹H and ²H signals persists in the gel phase, indicating that the lipid molecules retain a degree of reorientational freedom about their long axes in this phase. At the gel-liquid crystal transition the ²H quadrupole spittings undergo a discontinuous change. Results are interpreted in terms of a model in which water molecules are bound to individual lipid head groups and reorient with them, while sodium ions are located in the aqueous channel between bilayers.     

Amylase iso-enzymes in primates of the families Lemuridae,Cebidae, Cercopithecidae,Hylobatidae and Pongidae

This paper presents the first data in the alpha-amylase isoenzymes in primates of the families: Lemuridae, Cebidae, Cercopithecidae, Hylobatidae and Pongidae. By means of agar-gel electrophoresis of urine samples from 33 individuals belonging to ten species of the above mentioned families a total of 14 different variants of amylase heterogeneity were found.