Optimal allocation of building blocks between nutrient uptake systems in a microbe

 A bacterial cell must distribute its molecular building blocks among various types of nutrient uptake systems. If the microbe is to maximize its average growth rate, this allocation of building blocks must be adjusted to the environmental availabilities of the various nutrients. The adjustments can be found from growth balancing considerations. We give a full proof of optimality and uniqueness of the optimal allocation regime for a simple model of microbial growth and internal stores kinetics. This proof suggests likely candidates for optimal control regimes in the case of a more realistic model. These candidate regimes differ with respect to the information that the cells control system must have access to. We pay particular attention to one of the three candidates, a feedback regime based on a cellular control system that monitors only internal reserve densities. We show that allocation converges rapidly to balanced growth under this control regime. Received: 20 November 2000 / Revised version: 7 August 2001 / Published online: 21 February 2002     

Sequential rearrangements of ensemble activity of the putamen neurons of monkeys as a correlate to continuous behavior

Simultaneous recording of unit activity of 6-8 putamen neurons in two monkeys (M. nemestrina and M. mulatta) during performance of the task of alternative spatial choice, was carried out. The extent of rearrangements of the activity in the groups of neurons with the transition from every step of the behavioral program to the next one and the degree of difference in mosaics of reactivity, forming at every step with a different variants of performance, were evaluated using discriminative analysis. The rearrangements of the impulse activity were recorded in all steps of the program. The dynamics of rearrangements with the choice of right or left feeder was different, which resulted in appearance of significant differences in mosaics of reactivity at the stage of decision making and receiving reward. The rearrangements preceding the task-oriented movement of one hand were more pronounced in the contralateral hemisphere. The volume of rearrangements may increase with the performance of movement but the differences of mosaics formed during the movement of right and left hand are decreasing. At the stage of reception of the reward, the rearrangements were greater in case the animal chose the certain (left) feeder irrespective of the side of recording the unit activity.     

Dissociative mechanism of thermal denaturation of rabbit skeletal muscle glycogen phosphorylase b

The thermal stability of rabbit skeletal muscle glycogen phosphorylase b was characterized using enzymological inactivation studies, differential scanning calorimetry, and analytical ultracentrifugation. The results suggest that denaturation proceeds by the dissociative mechanism, i.e., it includes the step of reversible dissociation of the active dimer into inactive monomers and the following step of irreversible denaturation of the monomer. It was shown that glucose 1-phosphate (substrate), glucose (competitive inhibitor), AMP (allosteric activator), FMN, and glucose 6-phosphate (allosteric inhibitors) had a protective effect. Calorimetric study demonstrates that the cofactor of glycogen phosphorylase-pyridoxal 5'-phosphate-stabilizes the enzyme molecule. Partial reactivation of glycogen phosphorylase b preheated at 53 degrees C occurs after cooling of the enzyme solution to 30 degrees C. The fact that the rate of reactivation decreases with dilution of the enzyme solution indicates association of inactive monomers into active dimers during renaturation. The allosteric inhibitor FMN enhances the rate of phosphorylase b reactivation.     

The effect of a syringe-exchange program on a decrease in the risk of HIV infection among intravenous narcotic abusers in the city of Rostov-on-Don

The necessity and effectiveness of introducing the program of the exchange of syringes for intravenous drug users as a preventive and antiepidemic measure are discussed. Preventive and antiepidemic measures within the concept of harm reduction are described. The comparative analysis of materials obtained as a result of two sociological questionings, carried out in 1997-1998 among the representatives of the community (random nonrepeating choice) and in the middle of 1999 among the participants of the program revealed that the participants of the program had statistically significant changes in risky behavior patterns during the use of injection drugs.     

The expression of transmission ratio distortion (TRD) and the frequency of carriers of <Emphasis Type="Italic">t</Emphasis> haplotypes in natural populations of house mice <Emphasis Type="Italic">Mus musculus</Emphasis>

The character of TRD (transmission ratio distortion) was analyzed using the database formed on the basis of the results obtained for a collection of mice carrying different t haplotypes during 30 years of experimental observations. Quantitative TRD parameters were determined in male mice with T/t ^w genotypes from natural populations in crosses with females from laboratory collections. The TRD value varied in the range from 0.41 to 0.74. The frequencies of t haplotypes in natural Mus musculus populations from different regions (Moscow, Moscow oblast, Tajikistan, Lithuania, and Mongolia) varied from 12% (Tigrovaya Balka, Tajikistan) to 44% (Ulan-Bator, Mongolia). The factors and mechanisms determining a low frequency of t haplotypes in natural populations are discussed.     

Investigation of mechanism of p38 MAPK activation in renal epithelial cell from distal tubules triggered by cardiotonic steroids

Ouabain and other cardiotonic steroids (CTS) kill renal epithelial cells from distal tubules (C7-MDCK) via interaction with Na,K-ATPase but independently of inhibition of Na,K-ATPase-mediated ion fluxes. Recently, we demonstrated that modest intracellular acidification and inhibition of p38 MAPK suppress death of C7-MDCK cells triggered by ouabain. In the present study we investigate the mechanism of p38 MAPK activation in renal epithelial cell from distal tubules evoked by cardiotonic steroids. Using Na⁺/K⁺ ionophores (monensin, nigericin) and media with different content of monovalent cations, we revealed that p38 MAPK phosphorylation in ouabain-treated renal epithelial cells is not caused by Na,K-ATPase inhibition and inversion of the [Na⁺]_i/[K⁺]_i ratio. We also demonstrated that attenuation of pH from 7.45 to 6.75 did not alter the level of p38 MAPK phosphorylation observed in ouabain-treated cells. Inhibitors of PKA, PKC, and PKG as well as protein phosphatases were unable to abolish p38 MAPK activation triggered by ouabain. Using phosphotyrosine antibodies we did not detect any effect of ouabain on activation of tyrosine kinases. Thus, our results show that activation of p38 MAPK and cytotoxic action of CTS are independent of intracellular Na⁺, K⁺, and H⁺ concentrations. The molecular origin of intermediates of death signaling induced by CTS via conformation changes of Na,K-ATPase with following activation of p38 MAPK should be examined further.