Possible participation of nonimpulse factors in the increased excitability of partially deafferentated motor neurons

The dynamics of strengthening of monosynaptic segmental response (MSR) in white rats has been studied after bilateral sciatic nerves cuts nearer to the spinal cord (high cut) and farther from it (low cut). 24 hours after the operation the irritation of the posterior root on the side of the high cut stimulates anterior root MSR of authentically larger amplitude than on the side of the low cut and much greater than in intact animals. 48 h, 72 h and 120 h after the operation MSR amplitude on both sides is considerably increased in comparison with the intact animals amplitude but authentically does not differ on the side of the low and high cuts. A connection may be suggested between the excitability increase process of partially deafferented motoneurons with the disturbance of axoplasmatic flow in central sections of the cut afferent fibres.     

Possible chemical mechanisms underlying the antitumor activity of S-deoxyleinamycin

Though less potent than the parent natural product leinamycin, S-deoxyleinamycin displays activity against human cancer cell lines that is comparable to many clinically used agents. The results reported here suggest that the 1,2-dithiolan-3-one heterocycle found in S-deoxyleinamycin reacts with thiols to generate a persulfide intermediate (RSS(-)) that could deliver biologically active polysulfides, hydrogen sulfide, and reactive oxygen species (O2*-, H(2)O(2), and HO*) to the interior of cells.     

The structural organization and neurochemical mechanisms of the participation of the nucleus accumbens in the interaction of the limbic and motor systems and in the regulation of motor behavior]

The review of own and literature data devoted to structural and neurochemical organization of the nucleus accumbens (Acc) as well as spatial organization of their projection fibers in comparison with nucleus caudatus (neostriatum) has been presented. The facts concerned with correlations revealed between both the cell clusters and histochemical compartments as well as the compartmental organization of afferent and efferent striatal connections were analyzed. The presented data propose the existence of sensorimotor and limbic parts of the dorsal and ventral striatum, which are involved in the parallelly functioning systems. The common and different signs of these two systems and its role in the regulation of the movement behaviour has been proposed. A lot of attention also was payed to the Acc and the neostriatum interaction. The many pathways by which Acc can influence neostriatum functions and therefore the motor activity controlled by the neostriatum are discussed. It was shown that the Acc can influence on the striatal synaptic DA release. The sign of this influence depended upon DA/glutamic acid interactions in the Acc. It was stressed that the influence of Acc on striatal DA-ergic system is very likely mediated via kainate/quisqualate (but not NMDA) inputs of the neostriatum. The balance of DA-ergic mechanisms of neostriatum and Acc as important basis of animals adequate behaviour in conditioning situation was proposed. The disbalance of these mechanisms could leads to pathology.     

端粒酶活性调节的分子机制

人端粒酶由RNA亚基、hTERT催化亚基和hTEP1调节蛋白等组成。端粒酶对端粒结构的稳定起着重要的作用,而端粒结构和端粒结合蛋白也影响着端粒酶活性。某些化疗药物通过破坏端粒结构下调端粒酶活性。端粒酶的激活需要hTERT基因的从头转录和各个蛋白亚基正确装配为端粒酶全酶。端粒酶活性调节的分子机制包括：（1）TERT基因的表达和转录是决定端粒酶活性的重要环节,受多种因素调控;（2）蛋白激酶Cα和蛋白激酶B磷酸化端粒酶蛋白而激活端粒酶,蛋白磷酸酯酶2A（PP2A）可逆转这一过程,下调端粒酶活性;（3）多种癌基因和抑癌基因及其编码的蛋白质也直接或间接与端粒蛋白、端粒酶蛋白反应,参与端粒酶活性的调控。     

Possible mechanisms for antioxidant activity of glycyrrhizinic acid

Possible mechanisms of antioxidant activity of glycyrrhizinic acid (GA) were studied. GA did not exhibit antiradical properties in the experiments with stable radical 1,1-diphenyl-2-picrylhydrazyl at the concentration range of 1–100 μM. These data were confirmed by the study of GA effect on luminol chemiluminescence in a cell-free system in the presence of hydrogen peroxide. At the same time, GA decreases (in a dose-dependent manner) the generation of reactive oxygen species by neutrophils activated with both phorbol 12-myristate 13-acetate (PMA) and the chemotactic peptide, N-formyl-Met-Leu-Phe (FMLP). Using dichlorodihydrofluorescein (DCF) fluorescence it has been demonstrated that direct addition of GA to neuron culture did not decrease the level of free radical formation. However, preincubation of cells with GA resulted in the decrease in free radical production rate and increase in reduced intracellular glutathione level.     

Nervous regulation of abomasum motor activity in sheep

Pharmacological studies of abomasum motor activity were carried out in 3 sheep with chronic fistulae in the rumen and the fundus and pyloric part of the abomasum. The contractions of these parts of the stomach were recorded by the balloon method. The obtained results showed that in the abomasum stimulation of alpha-adrenergic receptors raises the degree of motor activity while stimulation of beta-adrenergic receptors inhibits it. It has been shown also that the sympathetic system has a greater influence through the beta-adrenergic receptors on the motor activity of the pyloric part than on that of the fundus of the abomasum. The analysis of the records obtained after bilateral vagotomy demonstrated that the automatism of the pyloric part was greater than that of the fundus of the abomasum.     

Molecular mechanisms of regulation of the macrophage activity

This review systematized modern conceptions of the most frequently occurring types of macrophage activation. Mechanisms of induction and regulation of these three types of activation were discussed. Any macrophage population was shown to easily change its properties depending on its microenvironment and concrete biological situation (functional plasticity of macrophages). Many intermediate functional states of macrophages were described, along with the most pronounced and well-known activation states (classical activation, alternative activation, and type II activation). These intermediate states were characterized by various compositions of their biological properties, including elements of all the three aforementioned types of activation. Macrophage activity was shown to be regulated by a complex network of interrelated cascade mechanisms.     

Possible mechanisms of normal amylase activity in hyperlipemic pancreatitis.

Lipemic serum from three patients with acute pancreatitis and type IV hyperlipemia was fractionated into very-low-density lipoproteins and clear serum. Amylase activity (determined by the Phadebas method) in the component fractions did not exceed that in the original lipemic serum. Addition of these fractions or VLDL and chylomicrons from asymptomatic patients with hyperlipemia to nonlipemic serum from patients with "routine acute pancreatitis" did not inhibit amylase activity or alter the electrophoretic mobility of amylase isoenzymes. Therefore the normal amylase activity often observed in hyperlipemic pancreatitis does not result from an inhibition of amylase activity by serum lipoproteins.     

The participation of CCK-8-ergic mechanisms in the regulation of emotional behavior in rodents

Effects of CCK-8 receptor agonists caerulein and pentagastrin and CCK-8 receptor antagonist proglumide on exploratory and locomotor activity of mice and rats were studied. Systemic administration of caerulein (500 ng/kg 1 mcg/kg) decreased significantly the exploratory activity of mice in elevated plus-maze. This anxiogenic-like action of caerulein was attenuated by acute pretreatment with proglumide (1 and 15 mg/kg) but not with diazepam (up to 0.75 mg/kg). Proglumide slightly increased the exploratory activity of rats in plus-maze; on the other hand, caerulein and pentagastrin potently decreased the measures of exploration in this test. Caerulein (10-100 mcg/kg) and proglumide (1 and 15 mg/kg) inhibited 3H-pentagastrin binding in mice brain in in vivo experiments. The data obtained indicate that CCK-8-ergic mechanisms in brain play an important role in the generation of anxiety states in rodents.     

Possible involvement of calmodulin in the regulation of ATPase activity in guard cells

Calcium ions play an important role in the regulation of stomatal movement and the mechanism underlying this action is yet to be determined. It is suggested that guard cell plasma membrane ATPase is a target for calcium action and that this effect is mediated by calmodulin. In this study, the effects of calcium and two calmodulin antagonists on ATPase activity in a crude homogenate of Commelina communis L. guard cell protoplasts were examined. The homogenate contained Mg²⁺-dependent, K⁺-simulated ATPase activity, which was inhibited by CaCl² while stimulated by the calmodulin antagonists, compound 48/80 and chlorpromazine. The calmodulin antagonists partially reversed the inhibitory effect of calcium ions. The results support the possibility of calmodulin involvement in the regulation of guard cell ATPase activity by calcium ions.     

Synaptic mechanisms of associative memory in the amygdala

Do associative learning and synaptic long-term potentiation (LTP) depend on the same cellular mechanisms? Recent work in the amygdala reveals that LTP and Pavlovian fear conditioning induce similar changes in postsynaptic AMPA-type glutamate receptors and that occluding these changes by viral-mediated overexpression of a dominant-negative GluR1 construct attenuates both LTP and fear memory in rats. Novel forms of presynaptic plasticity in the lateral nucleus may also contribute to fear memory formation, bolstering the connection between synaptic plasticity mechanisms and associative learning and memory.     

Effect of lesions of the medial and lateral portions of the amygdala on motor activity in rats

In four groups of rats: with medial amygdala lesions, AMe, sham operated medial, AMe-C, with lateral amygdala lesions, LA, and sham operated lateral, LA-C,--motor activity was tested in small electro-magnetic cages before and after ablations. The obtained data showed an increase of motor activity only in AMe rats. Possible functional differentiation of modulatory mechanisms of the amygdala is discussed.     

Studies of the molecular mechanisms in the regulation of telomerase activity.

Telomerase, a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes, is repressed in normal human somatic cells but is activated during development and upon neoplasia. Whereas activation is involved in immortalization of neoplastic cells, repression of telomerase permits consecutive shortening of telomeres in a chromosome replication-dependent fashion. This cell cycle-dependent, unidirectional catabolism of telomeres constitutes a mechanism for cells to record the extent of DNA loss and cell division number; when telomeres become critically short, the cells terminate chromosome replication and enter cellular senescence. Although neither the telomere signaling mechanisms nor the mechanisms whereby telomerase is repressed in normal cells and activated in neoplastic cells have been established, inhibition of telomerase has been shown to compromise the growth of cancer cells in culture; conversely, forced expression of the enzyme in senescent human cells extends their life span to one typical of young cells. Thus, to switch telomerase on and off has potentially important implications in anti-aging and anti-cancer therapy. There is abundant evidence that the regulation of telomerase is multifactorial in mammalian cells, involving telomerase gene expression, post-translational protein-protein interactions, and protein phosphorylation. Several proto-oncogenes and tumor suppressor genes have been implicated in the regulation of telomerase activity, both directly and indirectly; these include c-Myc, Bcl-2, p21(WAF1), Rb, p53, PKC, Akt/PKB, and protein phosphatase 2A. These findings are evidence for the complexity of telomerase control mechanisms and constitute a point of departure for piecing together an integrated picture of telomerase structure, function, and regulation in aging and tumor development-Liu, J.-P. Studies of the molecular mechanisms in the regulation of telomerase activity.     

NMR reveals novel mechanisms of protein activity regulation

NMR spectroscopy is one of the most powerful tools for the characterization of biomolecular systems. A unique aspect of NMR is its capacity to provide an integrated insight into both the structure and intrinsic dynamics of biomolecules. In addition, NMR can provide site-resolved information about the conformation entropy of binding, as well as about energetically excited conformational states. Recent advances have enabled the application of NMR for the characterization of supramolecular systems. A summary of mechanisms underpinning protein activity regulation revealed by the application of NMR spectroscopy in a number of biological systems studied in the lab is provided.     

Genetic mechanisms for the regulation of natural killer cell activity

The problems on genetic mechanisms of regulation of natural killer cells, participation of major histocompatibility complex in these processes are considered. The examples of mutations and hereditary diseases accompanied by disfunction of the natural killer activity are presented. It is supposed that genetic predisposition of natural killer activity depression can promote an increase in the risk of malignant and autoimmune diseases.