Tricyclic Imipramine Modification of the Circadian Rhythms of Hypothalamic Serotonin, its Precursors and Acid Catabolite in Individually Housed Rats

Circadian rhythms of serotonin (5HT), its precursors tryptophan (TP) and 5-hydroxy-tryptophan (5HTP) and its acid catabolite 5-hydroxy-indoleacetic acid (5HIAA), were determined in the hypothalamus of control rats and rats which had been treated continuously with subcutaneous imipramine (10 mg/kg/day) for 2 weeks.

Rats were individually housed and entrained to LD12:12. Controls showed the 5HT and TP peaks in the light and dark periods respectively, as reported in the literature, but no inverted correlation (antiphase) between SHT and 5HIAA rhythms.

Imipramine significantly modified circadian rhythm characteristics: the 5HT acrophase was advanced, that of TP and 5HIAA was delayed. Imipramine also significantly increased hypothalamic SHT and TP concentrations.     

Effect of Zeitgeber Intensity Reduction on a Simulated Dual-Oscillator Human Circadian System: Classical and Dynamic Analysis

The two-oscillator model of human circadian rhythmicity was analyzed when a zeitgeber relative intensity of 1, 0.5, or 0.1 was introduced into the equations. Fourier analysis was compared with dynamic analysis such as attractor reconstruction or Liapunov exponent calculation. After a 50 or 90% reduction in zeitgeber intensity, the dynamics of the system became equivalent and differed significantly from those of a system with maximal zeitgeber intensity. When 10% aleatory noise was added to the data, the analysis was still applicable, and the results obtained were essentially the same as in the absence of noise. Dynamic analysis could thus provide a distinct classification for periodic data, based on the type of analysis.     

A Brassica napus gene family which shows sequence similarity to ascorbate oxidase is expressed in developing pollen. Molecular characterization and analysis of promoter activity in transgenic tobacco plants

The genomic clone named Bp10 contains a member of a small pollen-specific gene family of B. napus. The expression of the Bp10 gene family is maximal in early binucleate microspores and declines considerably in mature trinucleate pollen. Homologues of the Bp10 genes are expressed in the pollen of other plant species. The pollen-specific expression of the gene contained in the genomic clone was confirmed in tobacco plants transformed with a chimeric Bp10 promoter/GUS construct. A promoter fragment of 396 bp is sufficient to direct a strong and correct spatial and temporal expression in transgenic plants. The Bp10 gene family codes for proteins of 62 kDa showing approximately 30% sequence identify to cucumber and pumpkin ascorbate oxidases (AAOs). However, the AAO active centres are not conserved in the Bp10 products, suggesting an evolutionary relationship but a different enzymatic activity for these proteins. Expression of a recombinant Bp10 protein in E. coli inhibits bacterial growth on minimal medium, suggesting the production of an enzymatically active polypeptide in bacteria. No AAO activity could be correlated with the expression of the recombinant protein. Moreover, substances affecting AAO activity do not appear to influence the inhibitory activity of the protein produced in bacteria. However, as indicated by the rescue of bacterial growth in the presence of sodium bicarbonate or gaseous CO2, the Bp10 protein activity could be modulated by CO2 levels.     

Treatment with natural human interferon alpha of a CML-patient with antibodies to recombinant interferon alpha-2b

A patient with Philadelphia-chromosome positive chronic myelogenous leukemia developed interferon antibodies on treatment with recombinant interferon alpha-2b. Clinically this event corresponded with progressive disease. No cross-reactivity of antibodies with human leukocyte interferon was found by Western blot. Treatment was switched to human leukocyte interferon with an obvious clinical effect: WBC was reduced and platelet count stabilized, but the effect was transient and no hematologic remission was achieved. Human leukocyte interferon may be an alternative in CML-patients with neutralizing antibodies to recombinant interferon alpha.     

Design and mathematical description of differential contactors used in extractive fermentations

The performance of differential contactors for use in extractive fermentation is complicated by the effects of product formation in the contactor. When product formation is significant, approximate analytical solutions are presented for the performance of the contactor for two limiting cases: high and low substrate concentrations. When products are formed at a constant rate, there is a minimum raffinate solute concentration that can be obtained, in contrast to the behavior of a column in the absence of product formation. General equations describing the behavior of the system for product formation with backmixing in both phases are presented. The case of a stripping factor not equal to unity is considered.     

The mechanistic nature of the membrane potential dependence of sodium-sugar cotransport in small intestine

Summary Methods are described which demonstrate the use of unidirectional influx of¹⁴C-tetraphenylphosphonium (¹⁴C-TPP⁺) into isolated intestinal epithelial cells as a quantitative sensor of the magnitude of membrane potentials created by experimentally imposed ion gradients. Using this technique the quantitative relationship between membrane potential () and Na⁺-dependent sugar influx was determined for these cells at various Na⁺ and -methylglucoside (-MG) concentrations. The results show a high degree of dependence for the transport Michaelis constant but a maximum velocity for transport which is independent of . No transinhibition by intracellular sugar (40mm) can be detected. Sugar influx in the absence of Na⁺ is insensitive to 1.3mm phlorizin and independent of . The mechanistic implications of these results were evaluated using the quality of fit between calculated and experimentally observed kinetic constants for rate equations derived from several transport models. The analysis shows that for models in which translocation is the potential-dependent step the free carrier cannot be neutral. If it is anionic, the transporter must be functionally asymmetric. A model in which Na⁺ binding is the potential-dependent step (Na⁺ well concept) also provides an appropriate kinetic fit to the experimental data, and must be considered as a possible mechanistic basis for function of the system.     

Feedback inhibition of homoserine dehydrogenase and threonine deaminase in the genusBifidobacterium

Feedback inhibition of crude and purified extracts of homoserine dehydrogenase and threonine deaminase activities in the genusBifidobacterium was studied. Homoserine dehydrogenase was partially or completely inhibited byl-threonine, and a marked inhibitory effect byl-isoleucine on threonine deaminase was observed. In the speciesBifidobacterium cuniculi high levels ofl-valine reversed the inhibitory effect ofl-isoleucine. The -aminobutyric acid-resistant mutant Ru 326/106 of the speciesB. ruminale, overproducer ofl-isoleucine, had a derepressed homoserine dehydrogenase and a lesser feedback inhibition byl-threonine. Homoserine dehydrogenase appeared to be in bifids specifically NAD dependent. The regulatory mechanisms of aspartate family amino acid biosynthesis in bifidobacteria was discussed.     

By-product inhibition effects on ethanolic fermentation by Saccharomyces cerevisiae

Inhibition by secondary fermentation products may limit the ultimate productivity of new glucose to ethanol fermentation processes. New processes are under development whereby ethanol is selectively removed from the fermenting broth to eliminate ethanol inhibition effects. These processes can concentrate minor secondary products to the point where they become toxic to the yeast. Vacuum fermentation selectively concentrates nonvolatile products in the fermentation broth. Membrane fermentation systems may concentrate large molecules which are sterically blocked from membrane transport. Extractive fermentation systems, employing nonpolar solvents, may concentrate small organic acids. By-product production rates and inhibition levels in continuous fermentation with Saccharomyces cerevisiae have been determined for acetaldehyde, glycerol, formic, lactic, and acetic acids, 1-propanol, 2-methyl-1-butanol, and 2,3-butanediol to assess the potential effects of these by-products on new fermentation processes. Mechanisms are proposed for the various inhibition effects observed.