Evidence for two distinct c-src loci on human chromosomes 1 and 20

A number of proto-oncogenes have recently been localized to the chromosomal segments that are the breakpoints in the specific rearrangements noted in human malignant diseases. Moreover, rearranged forms of several proto-oncogenes have been identified in malignant cells; in several instances, the proto-oncogene has undergone an alteration as a result of a nonrandom chromosomal rearrangement. One proto-oncogene that has yet to be associated with human neoplastic disease is c-src, the cellular homologue of the transforming sequence of Rous sarcoma virus (RSV). By somatic cell hybridization, c-src has been mapped to chromosome 20, but its precise location was not determined. We have now mapped this gene by using in situ hybridization of the cloned human c-src probe to human mitotic chromosomes. We report here that the human genome contains two loci with strong homology to the coding regions of this oncogene, at 1p34-p36 and 20q12-q13. It is noteworthy that these chromosomal regions are frequently involved in the structural rearrangements observed in haematological malignant diseases.     

New bone induction by demineralized bone matrix in immunosuppressed rats.

Subcutaneous implantation of demineralized bone matrix (DBM) initiates a sequence of developmental events which culminate in endochondral bone formation. To test the effects of T-cell deficiency on new bone formation, the morphology of DBM-induced bone was examined in rats thymectomized at three weeks of age and in thymectomized or nonthymectomized rats lethally irradiated and reconstituted with syngeneic bone marrow. At 24 days after implantation, bone induction in control rats was appropriate for their age, while thymectomized-irradiated-reconstituted rats and thymectomized rats had significantly more new bone and larger bone marrow space than the controls. In non-thymectomized, irradiated and reconstituted rats, bone induction occurred in only 25% of the animals, compared to 95% in other groups.     

Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A.

We have investigated the peripheral myelin protein gene, PMP-22, in a family with Charcot-Marie-Tooth disease type 1A (CMT1A). The DNA duplication commonly found in CMT1A was absent in this family, but strong linkage existed between the disease and the CMT1A marker VAW409R3 on chromosome 17p11.2. We found a point mutation in PMP-22 which was completely linked with the disease. The mutation, a proline for leucine substitution in the first putative transmembrane domain, is identical to that recently found in the Trembler-J mouse. The presence of this PMP-22 defect in this CMT1A family and the location of PMP-22 within the DNA duplication associated with CMT1A suggest that both structural alteration and overexpression of PMP-22 may lead to the disease.     

NMR study of parallel-stranded tetraplex formation by the hexadeoxynucleotide d(TG4T).

Multistranded DNA structures based upon guanine association have been proposed to be important in the structure of chromosome telomeres and in immunoglobulin class switching. Nucleic acids containing runs of guanine bases form a number of structures in vitro, including fold-back structures (Fig. 1a) and parallel-stranded quadruplex structures in DNA and RNA. The features of fold-back structures have now been determined at high-resolution. The different structures are probably based on a tetrad of hydrogen-bonded guanine bases (Fig. 1b), with buffer conditions and sequence effects mediating isomerization between the different forms. Here we use NMR spectroscopy to investigate the solution structure of the complex formed by the hexadeoxynucleotide d(TG4T) in the presence of sodium ions. We have observed the formation of a parallel-stranded quadruplex containing hydrogen-bonded tetrads of guanine. The parallel-stranded form differs significantly from the fold-back form, with individual nucleotide conformations being closer to those of B-form DNA.     

Quantification of the disorder in network-modified silicate glasses.

Local order in silicate glasses has been observed by many experimental techniques to be similar to that in crystalline materials. Details of the intermediate-range order are more elusive, but essential for understanding the lack of long-range symmetry in glasses and the effect of composition on glass structure. Two-dimensional 17O dynamic-angle-spinning nuclear magnetic resonance experiments reveal intermediate-range order in the distribution of inter-tetrahedral (Si-O-Si) bond angles and a high degree of order in the disposition of oxygen atoms around the network-modifying cations.     

Capillary electrophoresis: the promise and the practice.

The field of capillary electrophoresis has undergone rapid development over the past 10 years. Many advances have been made, but there are still some problems that must be addressed before the technique can reach its full potential.