Partial trisomy 11p with interatrial septal aneurysm. Case report and literature review

A newborn female infant presented with hypotonia, joint hyperextensibility, cardiac murmur, macroglossia, and hepatosplenomegaly. Karyotype of the child revealed partial trisomy of chromosome 11p derived from a paternal balanced translocation. Echocardiogram obtained in the newborn period suggested interatrial aneurysm, which was confirmed on post-mortem examination. Interatrial septal aneurysm is a rare abnormality not previously described in partial trisomy 11p.     

Proteins of demembraned mouse sperm heads. Characterization of a major sperm-unique component

A 15-kilodalton protein has been identified as a major component of the residual protein fraction of mouse epididymal/vas spermatozoal heads, demembraned by treatment with Triton X-100 and sequentially extracted with 1 M NaCl/2-mercaptoethanol/DNase I. Two-dimensional electrophoresis of that protein before and after treatment with alkaline phosphatase indicated that it is present in epididymal/vas spermatozoa as a series of five differentially phosphorylated molecules with pI 6.0-7.0. Cyto-immunofluorescence with an affinity-purified antibody to the 15-kDa protein localized that protein to a circumscribed region of the demembraned mouse sperm head mediad from the dorsal margin. By radioimmunoassay, the 15-kDa protein was shown to be sperm-unique and species-specific. The antibody was nonreactive with homogenates of meiotic spermatogenic cells and round spermatids (stages 1-11) but was reactive with a non-phosphorylated 15.5-kDa protein of elongating spermatids (stages 12-16) and testicular spermatozoa. Following alkaline phosphatase treatment, the spermatozoal 15-kDa protein migrated to the position of the spermatidal 15.5-kDa protein on a sodium dodecyl sulfate gel. Thus, we conclude that the 15-kDa protein of mouse spermatozoa is synthesized during the elongation phase of spermiogenesis (stages 12-16) and is phosphorylated in the terminal period of that phase and/or after excursion of spermatozoa from the seminiferous tubules.     

Phosphorylation of ankyrin decreases its affinity for spectrin tetramer

The effects of phosphorylation on the interaction between spectrin and ankyrin were investigated. Spectrin and ankyrin were phosphorylated using purified human erythrocyte membrane and cytosolic (casein kinase A) kinases. These two kinases have similar properties as well as activities toward spectrin and ankyrin. Both kinases catalyzed the incorporation of about 2 mol of phosphate/mol of spectrin and about 7 mol of phosphate/mol of ankyrin. These phosphates were incorporated primarily into seryl and threonyl residues of the proteins. The phosphopeptide maps of ankyrin phosphorylated by the membrane kinase and casein kinase A were identical. Binding studies indicate that ankyrin exhibits different affinities for spectrin dimers (KD = 2.5 +/- 0.9 X 10(-6) M) and tetramers (KD = 2.7 +/- 0.8 X 10(-7) M). These dissociation constants were not appreciably affected by the phosphorylation of spectrin. On the other hand, phosphorylation of ankyrin was found to significantly reduce its affinity for either phosphorylated or unphosphorylated spectrin tetramers (KD = 1.2 +/- 0.1 X 10(-6) M) but not spectrin dimers (KD = 2.5 +/- 0.4 X 10(-6) M). The same results were obtained using either the membrane kinase or casein kinase A as the phosphorylating enzyme. The above observation suggests that ankyrin phosphorylation may provide an important mechanism for the regulation of the erythrocyte membrane cytoskeletal network.     

Entry of methotrexate into Streptococcus pneumoniae: a study on a wild-type strain and a methotrexate resistant mutant

Entry of methotrexate (MTX) into the folate prototrophic bacterium Streptococcus pneumoniae was poorly inhibited by folate or its natural derivative folinic acid, suggesting that if MTX is transported via a folate transporter, the affinity of that transporter for MTX is higher than for folate. In the range of concentrations tested, MTX uptake was non-concentrative and decreased in ATP-depleted bacteria. When the external concentration of MTX was increased from 1 X 10(-7) M to 1 X 10(-6) M, uptake became saturated and was insensitive to ionophores. However when external MTX concentrations were increased to 1 X 10(-5) M, uptake increased linearly, and was inhibited by the ionophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and valinomycin, suggesting that the process was energized by the protonmotive force (delta p) at this concentration. A model for MTX entry in S. pneumoniae is proposed with respect to these results. The high level of resistance to MTX of the nonsense mutant amiA9 cannot be entirely explained by a decrease in MTX uptake.     

Simulation of conformational changes in 2 Zn insulin

Isolated insulin monomers, the dimer and higher aggregates from the 2 Zn crystal structure are subjected to convergent energy minimization in Cartesian co-ordinates using a force-field that includes the position of all hydrogen atoms. The minimizations are found, for the first time, to produce conformational changes of appreciable magnitude, which agree well with observed structural differences between monomers in the 2 Zn crystal and with the mechanism proposed previously for the coupling between deformations in different parts of the molecule. Our results also suggest that insulin would tend to adopt a molecule 1-like conformation in the absence of crystal packing forces, and that dimer formation is not at the origin of the observed asymmetry in the 2 Zn crystal.     

Spin probe clustering in human erythrocyte ghosts

Summary A model has been developed for 5-nitroxide stearate, I(12,3), distribution in human erythrocyte ghosts which accurately predicts ESR spectral alterations observed with increased probe/total lipid (P/L) at 37°C. This spin probe occupies a class of high-affinity, noninteracting sites at low loading. Saturation occurs with increasing probe concentration, and, at higher loading, the probe inserts itself at initially dilute sites to form membranebound clusters of variable size. No low probe remains at high P/L where all I(12,3) clusters in a concentrated phase. This model allows determination of the dilute/clustered probe ratio, and shows that I(12,3) segregates in erythrocytes at what might otherwise be considered low P/L (e.g., 1/359). These findings validate the earlier use of empirical parameters to estimate probe sequestration in biological membranes.     

Influence of the genetic background on cell division and cell lysis: behaviour of different Escherichia coli strains carrying the ts-52 or the ftsA-3 mutation

The analysis of Escherichia coli strains harbouring division mutations, namely the ts-52 or the ftsA-3 division alleles, in different genetic backgrounds showed that treatment with chloramphenicol in cells incubated at the restrictive temperature induced either cell lysis (ts-52 and ftsA-3 in MC-6 genetic background) or cell division (ts-52 in OV-2 genetic background). This chloramphenicol treatment of ftsA-3 filaments (previously designated at divA) does not induce cell division but does induce cell lysis.     

Study on the repair of the radioinduced lesions involved in the formation of chromosomal aberrations in G0 human lymphocytes after exposure to gamma-rays and fast neutrons

Cytosine arabinoside (ara-C), an inhibitor of DNA synthesis and repair, has been used to study the mechanisms of formation of chromosomal aberrations after exposure to low- and high-LET radiation. When G0 human lymphocytes were exposed either to gamma-rays or to d(50 MeV)-Be neutrons and immediately treated with ara-C for increasing periods of time, the frequency of aberrations (dicentrics) increased sharply. For gamma-rays, the enhancement increased with the duration of the treatment up to 5 h, whereas for neutrons, an ara-C treatment lasting for 5 h was no more effective than treatment for 3 h. These results were confirmed by the second experiment in which ara-C was administered for 3 h with an increasing time delay following irradiation. Since no increase in the dicentric frequency was observed when ara-C was administered 5 h after gamma-irradiation, it is suggested that the induced breaks rejoined within that time. For neutrons, the data were conflicting since the repair was completed within 3 h after a dose of 0.5 Gy, and in approximately 5 h after a dose of 2.0 Gy. From both experiments, it appears that gamma-rays and fast neutrons produce similar types of lesions, as ara-C increased the frequencies of aberrations induced by both types of radiation. However, the ara-C treatment resulted in a smaller increase in aberrations following neutron irradiation. According to the enzymatic nature of break formation and the mode of action of ara-C on the polymerase activity, it is suggested that, in addition to double-strand breaks, single-strand breaks could be the lesions involved in the repair processes inhibited by ara-C. Single-strand breaks formed directly or by secondary reactions would, therefore, be one of the major lesions responsible for the aberrations produced by gamma and neutron radiations.     

Genetic variation in a semi-natural Drosophila population after a bottleneck I. Lethals,their allelism and effective population size

A semi-natural Drosophila melanogaster population was twice forced through a genetic bottleneck and allowed to recover naturally. In one case additional variation was introduced to the recovering population. The percentage of lethal chromosomes, the level of allelism between these lethals, and the effective population size calculated from the allelism of these lethals all rose sharply in the few generations following each bottleneck, though this was not the case in the very first generation. Thereafter this rise decelerated rapidly and never returned to pre-bottleneck levels. Additional introduced variation had little effect. The reasons for and implications of this pattern have been considered.