Biogenic monoamines of the brain and spinal cord pia mater in vertebrates

Fluorimetric studies have been made on the content of adrenalin, noradrenaline, serotonin, dopamine, and tryptamine in the pial matter of the brain and spinal cord of fishes, birds and mammals including man. Using histochemical method with glyoxylic acid, biogenic monoamines were revealed in the adrenergic nerve fibers and monoaminocytes. Their total content in the pial matter of the brain is approximately the same in all vertebrates, being significantly lower in man. Higher concentration of adrenergic axons and lower amount of monoaminocytes in human subjects reveal the key role of the nervous influences in regulation of hemodynamics of the brain.     

Synthesis of purine N9-[2-hydroxy-3-O-(phosphonomethoxy)propyl] derivatives and their side-chain modified analogs as potential antimalarial agents

6-Oxopurine acyclic nucleoside phosphonates (ANPs) have been shown to be potent inhibitors of hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT), a key enzyme of the purine salvage pathway in human malarial parasites. These compounds also exhibit antimalarial activity against parasites grown in culture. Here, a new series of ANPs, hypoxanthine and guanine 9-[2-hydroxy-3-(phosphonomethoxy)propyl] derivatives with different chemical substitutions in the 2'-position of the aliphatic chain were prepared and tested as inhibitors of Plasmodium falciparum (Pf) HGXPRT, Plasmodium vivax (Pv) HGPRT and human HGPRT. The attachment of an hydroxyl group to this position and the movement of the oxygen by one atom distal from N(9) in the purine ring compared with 2-(phosphonoethoxy)ethyl hypoxanthine (PEEHx) and 2-(phosphonoethoxy)ethyl guanine (PEEG) changes the affinity and selectivity for human HGPRT, PfHGXPRT and PvHGPRT. This is attributed to the differences in the three-dimensional structure of these inhibitors which affects their mode of binding. A novel observation is that these molecules are not always strictly competitive with 5-phospho-α-d-ribosyl-1-pyrophosphate. 9-[2-Hydroxy-3-(phosphonomethoxy)propyl]hypoxanthine (iso-HPMP-Hx) is a very weak inhibitor of human HGPRT but remains a good inhibitor of both the parasite enzymes with K(i) values of 2μM and 5μM for PfHGXPRT and PvHGPRT, respectively. The addition of pyrophosphate to the assay decreased the K(i) values for the parasite enzymes by sixfold. This suggests that the covalent attachment of a second group to the ANPs mimicking pyrophosphate and occupying its binding pocket could increase the affinity for these enzymes.     

Conference reports third Bioclimatological Conference in Prague,Czechoslovakia 4–7 October 1961

International Journal of Biometeorology -     

Functional morphology of the rat thyroid during the first months of the pubertal period

Morphofunctional parameters of the rat thyroid gland, at the light optic and electron microscopic levels, during first months of the pubertal period are not stable. Quantitative values of these parameters fluctuate with a period of 32-36 days. Some morphofunctional parameters, such as diameter of the thyrocyte nucleus and content of albumine-binding iodine in blood, depend on the animal's body mass, other parameters do not depend on it.     

Sources of Variability in a Synthetic Gene Oscillator

Synthetic gene oscillators are small, engineered genetic circuits that produce periodic variations in target protein expression. Like other gene circuits, synthetic gene oscillators are noisy and exhibit fluctuations in amplitude and period. Understanding the origins of such variability is key to building predictive models that can guide the rational design of synthetic circuits. Here, we developed a method for determining the impact of different sources of noise in genetic oscillators by measuring the variability in oscillation amplitude and correlations between sister cells. We first used a combination of microfluidic devices and time-lapse fluorescence microscopy to track oscillations in cell lineages across many generations. We found that oscillation amplitude exhibited high cell-to-cell variability, while sister cells remained strongly correlated for many minutes after cell division. To understand how such variability arises, we constructed a computational model that identified the impact of various noise sources across the lineage of an initial cell. When each source of noise was appropriately tuned the model reproduced the experimentally observed amplitude variability and correlations, and accurately predicted outcomes under novel experimental conditions. Our combination of computational modeling and time-lapse data analysis provides a general way to examine the sources of variability in dynamic gene circuits.     

Influence of peroxidation products of liposomal lipids on antibacterial activity of liposomes]

The dynamics of accumulation of lipid peroxidation products (LPPs) in suspensions of phosphatidyl choline-cholesterol liposomes at various acidity levels was studied. It was shown that intensity of the accumulation of LPPs was inversely proportional to the suspension pH. When the liposomes were incubated together with the cells of Pseudomonas aeruginosa, there was a decrease in the level of LPPs in comparison to that in the suspension which did not contain bacterial cells. The accumulation of LPPs in the incubation medium correlated with the bacteria death rate in the suspension. There was a direct relationship of the antibacterial activity of the liposomal suspension on its content of LPPs.     

Finite volume and asymptotic methods for stochastic neuron models with correlated inputs

We consider a pair of stochastic integrate and fire neurons receiving correlated stochastic inputs. The evolution of this system can be described by the corresponding Fokker?CPlanck equation with non-trivial boundary conditions resulting from the refractory period and firing threshold. We propose a finite volume method that is orders of magnitude faster than the Monte Carlo methods traditionally used to model such systems. The resulting numerical approximations are proved to be accurate, nonnegative and integrate to 1. We also approximate the transient evolution of the system using an Ornstein?CUhlenbeck process, and use the result to examine the properties of the joint output of cell pairs. The results suggests that the joint output of a cell pair is most sensitive to changes in input variance, and less sensitive to changes in input mean and correlation.     

Timing and Variability of Galactose Metabolic Gene Activation Depend on the Rate of Environmental Change

Modulation of gene network activity allows cells to respond to changes in environmental conditions. For example, the galactose utilization network in Saccharomyces cerevisiae is activated by the presence of galactose but repressed by glucose. If both sugars are present, the yeast will first metabolize glucose, depleting it from the extracellular environment. Upon depletion of glucose, the genes encoding galactose metabolic proteins will activate. Here, we show that the rate at which glucose levels are depleted determines the timing and variability of galactose gene activation. Paradoxically, we find that Gal1p, an enzyme needed for galactose metabolism, accumulates more quickly if glucose is depleted slowly rather than taken away quickly. Furthermore, the variability of induction times in individual cells depends non-monotonically on the rate of glucose depletion and exhibits a minimum at intermediate depletion rates. Our mathematical modeling suggests that the dynamics of the metabolic transition from glucose to galactose are responsible for the variability in galactose gene activation. These findings demonstrate that environmental dynamics can determine the phenotypic outcome at both the single-cell and population levels.