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.     

Probabilistic and multiple regression modeling of the biologist’s decision processes and its implications for medical diagnosis

Current psychological research into the inference (diagnostic) process is briefly reviewed, using as a vehicle an investigation of the prediction of the probability of success of hypothetical applicants to a graduate program in biology. Brunswik’s lens model and multiple regression analysis are used, as is a Bayesian approach. Four judges’ (biologists’) predictions are analyzed. Some general conclusions about inference, drawn from the current data in psychology, are presented. This investigation was supported by PHS Research Grant No. MH-17487-01 from the National Institute of Mental Health.     

Computerized Entry into Medical Care—Its Impact on Doctor-Patient Relationships

A large proportion of cannery workers see a doctor only as a last resort, in time of crisis. The Cannery Workers Multiphasic Screening Program identified workers in need of physician evaluation, and referred each to a physician of his choice, for examination by appointment, while the worker was not acutely ill. In many instances the screening program generated the first encounters between patient and physician. It conducted a follow-up system for workers unaccustomed to methodical health care. The program financed pretesting education of the persons to be tested, multiphasic testing, physician evaluation of abnormal findings, and the follow-up reminder system.Each physician, in advance of the appointment for evaluation, was sent a computerized report calling attention to findings that exceeded limits considered normal. The report included a form facilitating the physician''s report and billing. In counties having foundations for medical care, the foundations reviewed the form for adequacy of follow-up and appropriateness of charges.The effort to bridge the gap between findings, diagnosis and therapy, for a population group newly introduced to modern medical care delivery, was made possible by the use of the computer as a tool for the attainment of specific, preanalyzed components of the total objective.     

Rat liver alcohol dehydrogenase. Purification and properties

Alcohol dehydrogenase (EC 1.1.1.1) from the rat liver supernatant fraction has been purified 200-fold and partially characterized. The isolation procedure involved ammonium sulphate fractionation, DEAE-Sephadex chromatography and gel filtration. The purified enzyme behaved as a homogeneous preparation as evaluated by cellulose acetate and polyacrylamide-gel disc electrophoresis. Sulphoethyl-Sephadex chromatography and immunoelectrophoresis with rabbit antiserum indicated the presence of a minor component. Rat liver alcohol dehydrogenase appears to contain 4mol of zinc/mol, has an estimated molecular weight of 65000 and consists of two subunits of similar molecular weight. Heavy-metal ions, thiol-blocking reagents, urea at concentrations below 8m, low pH (5.5) and chelating agents deactivate the enzyme but do not dissociate it into subunits. Deactivated enzyme could not be reactivated. The enzyme is strictly specific for NAD(+) and has a broad specificity for alcohols, which are bound at a hydrophobic site. Inhibition occurred with the enzyme equilibrated with Zn(2+) at concentrations above 0.1mm.     

Induced Bivalent Interlocking and the Course of Meiotic Chromosome Synapsis

WHEN chromosomes pair at meiosis the bivalents so formed do not normally interlock. Heat-treatments can, however, induce bivalent interlocking in the locust Locusta migratoria. Only the longest bivalents interlock and usually only two are found per cell; two “rod” bivalents, with single chiasmata, two “ring” bivalents, each with two or three chiasmata, or one “rod” and one “ring” bivalent (Fig. 1a, b and c). The nature of this interlocking and the metaphase orientational and congressional properties of interlocked bivalents are analysed in detail elsewhere¹.     

Histidyl-Transfer Ribonucleic Acid Synthetase in Positive Control of the Histidine Operon in Salmonella typhimurium

Autolysin-like enzymes appear to be responsible for cell separation in Agmenellum quadruplicatum. Mutants that are impaired in cell separation and grow as chains exhibit reduced cell lytic activity. Lysozyme, extracted autolysin, and antibiotics that affect peptidoglycan synthesis phenotypically suppress chain formation. Various aspects of the regulation of the cell separation process were also examined. Studies involving antibiotic inhibitors of macromolecular synthesis and general growth inhibitors provided no evidence for the active regulation of the cell separation process during the latter portion of the division cycle. Evidence was obtained, however, for the partial restriction of peptidogly-can hydrolysis by unknown secondary modifications. The thin electron-dense layer of peptidoglycan along the sides of cells was much more resistant to hydrolysis by egg-white lysozyme than was the septum between daughter cells. The middle portion of the septum was more sensitive than was the layer immediately adjacent to the cytoplasmic membrane. Under conditions that would not osmotically stabilize spheroplasts, lysozyme facilitates rapid cell separation in chain-forming mutants with little leakage of cellular protein or loss of viability.     

Climatic adaptation in recently shorn merino sheep

Heart rates, respiratory rates, body temperatures, ad libitum ‘day’ and ‘night’ food consumption and body weight changes have been examined in 15 mature Merino wethers shorn in moderate environmental conditions. All sheep showed a depression in food consumption for two days after shearing. Sheep that gained weight during the next three weeks then increased their food consumption at night by approximately 30% although the average daily consumption was only increased by 5%. Sheep that lost weight showed a depressed food consumption throughout the three week period after shearing. Marked increases in the temperature difference between ear skin and air as well as thermal tachypnoea during the warmest period of the day were recorded in all sheep 14–16 days after shearing. This indicated that the critical temperature for all sheep had decreased by about 10°C. These signs of acclimatisation appeared at similar times in all sheep, suggesting that increased resistance to body cooling developed at similar rates in weight gain and weight loss sheep and independent of the origin of body heat production. The results of the investigations are discussed in relation to the concept that the initial response to cold stress includes a depression in food intake and that the duration of this depression is a function of the cold stimulus and the strain it induces in the sheep.     

Transport of Biosynthetic Intermediates: Regulation of Homoserine and Threonine Uptake in Escherichia coli

Homoserine is transported by a single system that it shares with alanine, isoleucine, leucine, phenylalanine, threonine, valine and perhaps cysteine, methionine, serine, and tyrosine. We investigated the regulation of this transport system and found that alanine, isoleucine, leucine, methionine, and valine each repress the homoserine-transporting system. From the concentration resulting in 50% repression of this transport system and the maximal amount of repression, we ranked the amino acids according to their effectiveness in repressing homoserine transport (in decreasing order): leucine>methionine>alanine>valine>isoleucine. The exponential rate of decrease in transport capacity after leucine addition equals the exponential growth rate of the culture, and protein synthesis is necessary for the derepression seen when leucine is removed. Threonine, in addition to using the above system, is transported by a second system shared with serine. We present further evidence for this serine-threonine transport system and show that it is not regulated like the homoserine-transporting system.