Microcin C: Biosynthesis,Mode of Action,and Potential as a Lead in Antibiotics Development

The natural compound Microcin C (McC) is a Trojan horse inhibitor of aspartyl tRNA synthetases endowed with strong antibacterial properties, in which a heptapeptide moiety is responsible for active transport of the inhibitory metabolite part into the bacterial cell. The intracellularly formed aspartyl AMP analogue carries a chemically more stable phosphoramidate linkage, in comparison to the labile aspartyl-adenylate, and in addition is esterified with a 3-aminopropyl moiety. Therefore, this compound can target aspartyl-tRNA synthetase. The biochemical production and secretion of McC, and the possibilities to develop new classes of antibiotics using the McC Trojan horse concept in combination with sulfamoylated adenosine analogues will be discussed briefly.     

Phylogenetic analyses of primate size evolution: the consequences of sexual selection

We have analysed the relationship between primate mating system, size and size dimorphism by utilizing several phylogenetically based methods. An independent contrast analysis of male and female size (log weight) showed that these are tightly correlated and that size dimorphism is not a simple allometric function of size. We found no relationship between mating system and sexual dimorphism in strepsirhines but a strong relationship in haplorhines. By matched-pairs analysis, where sister groups were matched according to whether the mating system predicted higher or lower intrasexual selection for male size, haplorhine species in more polygynous clades (with a predicted higher sexual selection) were significantly more dimorphic, had larger males, and also, but to a lesser degree, larger females. Both independent contrast and matched-pairs analyses are non-directional and correlational. By using a directional test we investigated how a transition in mating system affects size and dimorphism. Here, each observation is the sum of changes in dimorphism or size in a clade that is defined by a common origin of a mating system. Generally, dimorphism, as well as male and female size, increased after an expected increase in sexual selection, and decreased after an expected decrease in sexual selection. The pattern was, however, not significant for all of the alternative character reconstructions. In clades with an expected increase in sexual selection, male size increased more than female size. This pattern was significant for all character reconstructions. The directional investigation indicates that the magnitude of change in haplorhine dimorphism is larger after an increase in sexual selection than after a decrease, and, for some reconstructions, that the magnitude of size increase is larger than the magnitude of size decrease for both sexes. Possible reasons for these patterns are discussed, as well as their implications as being one possible mechanism behind Cope's rule, i.e. general size increase in many phylogenetic lineages.     

Influence of α-interferon therapy on blood lymphoid cells

Summary The influence of natural -interferon (-IFN) therapy (3×10⁶ units i.m. daily) on blood lymphoid cells was studied in 20 patients with gynecological neoplasias (7 patients with condylomata accuminata and 13 patients with ovarian carcinoma). There was a statistically significant increase in the intracellular levels of 2'–5'oligoadenylate synthese 1 day after the first injection of IFN and with few exceptions this activity remained increased during 3 months of treatment. In most of the patients, the capacity of blood lymphoid cells to produce IgA, IgG, and IgM following stimulation with pokeweed mitogen was decreased 1 day after the first injection of IFN and with few exceptions it remained low during 6 months of IFN therapy. In most patients there was a decrease in the capacity of lymphoid cells to act as stimulator or responder cells in a mixed lymphocyte culture during IFN therapy. The -IFN therapy had no major influence on the response of lymphoid cells to mitogens. We conclude, that neither this nor our previous studies on the influence of IFN therapy on immunological functions have given support to the hypothesis that the antitumor action of IFN is mediated by the immune system.     

Possible mechanism of the allosteric activation of cAMP receptor protein

Secondary structure of cAMP receptor protein of E. coli was predicted and compared to its crystal structure in the complex with cAMP solved by McKay and Steitz. The two conformations coincide in the DNA binding domain but strikingly differ in the other domain which binds cAMP and causes protein dimerization. The comparison indicates that cAMP destabilizes a very long helix instead of which sheets are formed creating a hydrophobic pocket where cAMP binds. Consequently, the helix-sheets isomerization and a resulting change in the relative monomer disposition in the dimer appears to be the origin of cAMP-induced allosteric activation of the protein. Extremely long helices were also predicted in the regions of the regulatory subunit of cAMP-dependent protein kinase from bovine cardiac muscle where cAMP binds. It is thus likely that the proposed mechanism of the effect of cAMP on protein structure has wider implications.     

Urinary excretion of mandelic and phenylglyoxylic acids after human exposure to styrene vapour

The kinetics of the urinary excretion of mandelic and phenylglyoxylic acids were studied in volunteers exposed to the known concentrations of styrene vapour. The level and the time of exposure were suitably changed to simulate situations in the industrial environment. The aim was to find out the reasons for the contradictory reports in the literature and to verify parameters characterizing the course of excretion of both metabolites. It was found that the course of mandelic acid excretion might be influenced by the length of styrene exposure. If exposure was longer than 4 hours the maximum of excretion was at the end of the exposure time; after short-term exposures (4 h or less) it was somewhat delayed. Maximum excretion of phenylglyoxylic acid was delayed both after short-term and 8-hour exposures. Excretion of the metabolites was diphasic (biexponential). The effective half-lives were found to be independent of the level of exposure. The apparent half-lives (determined in the post-exposure time of 0-16 hours) tended to become prolonged at daily repeated exposures. The ratio of mandelic to phenylglyoxylic acid changed considerably with the level of exposure. In biological monitoring it is advisable to determine both metabolites.     

Model-based control of feed rate and illuminance in a photosynthetic fed-batch reactor for H2S removal

Traditional application of computer to fermentation processes has focused on the measurement and control of parameters such as temperature, pH, vessel pressure, sparge rate, dissolved oxygen, substrate concentration, and product concentration. In a fed-batch reactor with the photosynthetic green sulfur bacterium Chlorobium thiosulfatophilum which converts hydrogen sulfide to elementary sulfur or sulfate, separate measurement of cell mass concentration and sulfur particle concentration turbidimetrically was difficult due to their combined contributions to the total turbidity. Instead of on-line measurement of many process variables, a model-based control of feed rate and illuminance was designed. Optimal operation condition relating feed rate vs. light intensity was obtained to suppress the accumulation of sulfate and sulfide, and to save light energy in a 4-1 photosynthetic fed-batch reactor. This relation was correlated with the inreasing cell mass concentration. A model which describes the cell growth by considering the light attenuation effects due to scattering and absorption, and to crowding effect of the cells, was established beforehand with the results from the experiments. Based on these optimal operating conditions and the cell growth model, automatic controls of feed rate and illuminance were carried out alternatively to the traditional application of computer to fermentation with on-line measurement, realtime response and adjustment of process variables.List of Symbols F ml/min Flow rate of gas mixture - hV lux Average illuminance - Q mmol/(l h) Removal rate of hydrogen sulfide - X mg protein/l Cell mass concentration as protein - X ₀ mg protein/l Initial cell mass concentration - X _m mg protein/l Maximum cell mass concentration - _a h^–1 Apparent specific growth rate