Inhibition of DNA Synthesis but not of Poly-dAT Synthesis by the Arabinose Analogue of Cytidine <Emphasis Type="Italic">in vitro</Emphasis>

Kimball and Wilson¹ reported that the arabinose analogue of cytidine (ara-C) inhibited DNA polymerase in a crude extract prepared from Ehrlich ascites cells. Furth and Cohen² observed cytosine arabinoside triphosphate (ara-CTP) inhibited DNA polymerase in extracts from either calf thymus or bovine lymphosarcoma tissue, although these investigators³ had already found no effect of ara-CTP on DNA polymerase from Escherichia coli. The inhibition in both of these cases could be substantially reversed by dCTP; but incorporation of the arabinose nucleotide (ara-CMP) into DNA could not be unequivocally demonstrated. Graham and Whitmore⁴ reported the incorporation of ara-C into DNA in vivo and the inhibition of a DNA polymerase from L cells by ara-CTP. They found that ara-CMP was initially incorporated into small DNA strands but subsequently appeared in long strands. Momparler⁵ has presented evidence that, in vitro, ara-C incorporation was limited to the 3′-hydroxyl end of DNA chains. Such incorporation might be expected to block further chain elongation but this expectation was not supported by the evidence presented by Graham and Whitmore.     

Endopeptidase Activity of Phage λ-Endolysin

JACOB and Fuerst^1,2 demonstrated the presence of a bacteriolytic enzyme (λ-endolysin) in the induced cultures of lysogenic Escherichia coli K12 (λ). The enzyme was later identified as the product of gene R; of phage λ³ which is involved in bacterial lysis at the end of a latent period. The enzyme is apt to form spheroplast-like structures in E. coli² and one would therefore expect its substrate to be murein.     

Detection and Identification of Translocations by Increased Specific Nondisjunction in ASPERGILLUS NIDULANS

A meiotic technique for visual detection of translocations has been applied to ten mitotically identified interchanges, and three new translocations were discovered using this method. Testcrosses between "standard" strains and potential translocation strains-e.g. strains with newly induced mutants or descendants from translocation crosses-are inspected for the frequency of abnormal-looking colonies. In all heterozygous translocation crosses "abnormals" are increased at least tenfold compared to the average control level of 0.15%. Most of these are disomics, and can be recognized by their characteristic phenotypes. Each translocation produces a few specific types, since nondisjunction is increased mainly in the linkage groups involved in the translocation (50-100-fold over control values). Therefore, translocations were not only detected but often tentatively assigned to linkage groups from the analysis of the disomic progeny in crosses. In addition, this technique allows reciprocal and nonreciprocal translocations to be distinguished, since only the latter produce one-third phenotypically abnormal duplication progeny. While results are clearcut in most cases, occasionally problems are encountered, e.g. when morphological mutants segregate in crosses, or when other genetic factors which increase or reduce the frequency of nondisjunction are present in certain strains.     

Analysis of selection in populations observed over a sequence of consecutive generations

Summary A statistical model is presented for dealing with genotypic frequency data obtained from a single population observed over a run of consecutive generations. This model takes into account possible correlations that exist between generations by conditioning the marginal probability distribution of any one generation on the previously observed generation. Maximum likelihood estimates of the fitness parameters are derived and a hypothesis testing framework developed. The model is very general, and in this paper is applied to random-mating, selfing, parthenogenetic and mixed random-mating and selfing populations with respect to a single locus, g-allele model with constant genotypic fitness differences with all selection occurring either before or after sampling. The assumptions behind this model are contrasted with those of alternative techniques such as minimum chi-square or unconditional maximum likelihood estimation when the marginal likelihoods for any one generation are conditioned only on the initial conditions and not the previous generation. The conditional model is most appropriate when the sample size per generation is large either in an absolute sense or in relation to the total population size. Minimum chi-square and the unconditional likelihood are most appropriate when the population size is effectively infinite and the samples are small. Both models are appropriate when the samples are large and the population size is effectively infinite. Under these last conditions, the conditional model may be preferred because it has greater robustness with respect to small deviations from the underlying assumptions and has a greater simplicity of form. Furthermore, if any genetic drift occurs in the experiment, the minimum chi-square and unconditional likelihood approaches can create spurious evidence for selection while the conditional approach will not. Worked examples are presented.This study was supported in part by the U. S. Atomic Energy Commission, Contract AT (11-1) -1552 to the Department of Human Genetics (CFS), University of Michigan, and by National Science Foundation Grant BMS 74-17453 awarded to the author.     

Isolation of salt-soluble elastin from ligamentum nuchae of copper-deficient calf

This paper describes the isolation and amino acid analysis of un-cross-linked elastin obtained by neutral salt extraction from the ligamentum nuchae of a calf fed from birth to 9 months on a diet low in copper.     

The homogenous γG-immunoglobulin produced by mouse plasmacytoma 5563 and its subsequent heterogeneity in serum

The mouse plasma cell tumour 5563 has been shown to synthesize and secrete a single molecular species of gammaG-immunoglobulin, which was identified by labelling with (14)C-labelled amino acids. The heterogeneity of G-myeloma globulin as it is found in serum of tumour-bearing mice is due to subsequent changes in the charge properties of the newly secreted molecules. These changes have been reproduced in vitro. On incubation with sterile serum, the newly formed radioactive myeloma protein changed its chromatographic and electrophoretic properties to coincide with those of myeloma protein isolated from serum. Incubation of purified myeloma protein band a, under a variety of conditions, led to the characteristic pattern of serum myeloma protein showing multiple electrophoretic bands. The chemical nature of the molecular changes is not yet known. It is suggested that seruminduced changes could contribute to the electrophoretic heterogeneity of specific antibodies within the gammaG-class of immunoglobulins. This demonstration of the production of a single molecular species of immunoglobulin by a plasma cell tumour provides support for the concept of ;one-cell-one antibody'.