Chemokines--a new family of cytokines regulating leukocyte migration

A new group of cytokins, having the properties of chemoattractants and named "chemokins", has been characterized. These structurally related low-molecular proteins (8-10 kD) with 20-90% homology in amino acids contain 4 conservative disulfide-linked cysteins whose location determines which of the groups (CXC, CC, C) they belong to. Chemokins regulate the migratory activity of all types of leukocytic cells. Target cells are affected by chemokins through specific receptors (at least 9 types) of the rhodopsin family, including 7 transmembrane domains. Chemokins play an important role in the pathogenesis of many diseases, especially those of inflammatory nature. Some chemokins (RANTES, MIP-1) and their receptors are linked with the development of HIV infection. Chemokins serve as the basis of medicinal preparations, blocking or enhancing the migratory activity of leukocytes. Our newly developed preparation, based on a complex of natural cytokins, induces, when used locally, the influx of neutrophils and macrophages to the zone of tissue destruction, acting as chemokins.     

Up-regulation of myocardial connexin-43 in spontaneously hypertensive rats fed red palm oil is most likely implicated in its anti-arrhythmic effects

The purpose of this study was to test our hypothesis that red palm oil (RPO) intake may affect abnormalities of myocardial connexin-43 (Cx43) and protein kinase Cε (PKCε) signaling, and consequently the propensity of the spontaneously hypertensive rat heart (SHR) heart to arrhythmias. SHR and Wistar-Kyoto (WKY) rats fed a standard rat chow plus red palm oil (200?μL/day) for 5?weeks were compared with untreated rats. Cytosolic but not particulate PKCε expression as well as Cx43-mRNA, total Cx43 proteins, and its phoshorylated forms were increased, and disordered localization of Cx43 was attenuated in the left ventricle of RPO-fed SHR compared with untreated rats. These alterations were associated with suppression of early post-ischemic-reperfusion-related ventricular tachycardia and electrically inducible ventricular fibrillation. However, the treatment dose of RPO caused down-regulation of myocardial Cx43, but did not alter its cell membrane distribution or overall PKCε expression in WKY rats. It was, however, associated with poor arrhythmia protection, suggesting overdosing. Results indicate that SHR benefit from RPO intake, particularly because of its apparent anti-arrhythmic effects. This protection can be, in part, attributed to the preservation of cell-to-cell communication via up-regulation of myocardial Cx43, but not with PKCε activation.     

A special case of learning disruption as a model of a disintegration phenomenon

Combination of two factors in rats such as the isolation (during 2-4 months, beginning from the 21st day of age) and procedure of space cyclic learning results in a rare kind of behavioral strategy (in 30% animals), when the cyclic behavior is realized without food reinforcement. Such a dissociation between the vital motivation and searching behavior may be considered as an analogue of the disintegration phenomenon in neuropsychotic patients. The deep depression of learning owing to lowering of search represents the dominant type of behavioral disorders in isolants. The cyclic habit training, including a 2-months pause between two sessions, significantly increases behavioral search activity. The behaviors are accompanied by morphological shifts in the sensomotor cortex: significant decrease of the fifth layer (giant pyramids) thickness, selective lowering in the satellite glia density and elimination of normal behavior-glia correlations.     

Mutants of Burkholderia cenocepacia with a change in synthesis of N-acyl-homoserine lactones--signal molecules of Quorum Sensing regulation

By means of plasposon mutagenesis, mutants of Burkholderia cenocepacia 370 with the change in production of N-acyl-homoserine lactones (AHL), signal molecules of the Quorum Sensing system of regulation, were obtained. To localize plasposon insertions in mutant strains, fragments of chromosomal DNA containing plasposons were cloned, adjacent DNA regions sequenced, and a search for homologous nucleotide sequences in the GeneBank was initiated. It has been shown that the insertion of plasposon into gene lon encoding lon proteinase drastically decreases AHL synthesis. Upon insertion of plasposon into gene pps encoding phosphoenolpyruvate-synthase, enhancement of AHL production is observed. In mutant carrying inactivated gene lon, a strong decline of extracellular protease activity, hemolytic, and chitinolytic activities was observed in comparison with the original strain; lipase activity was not changed in this mutant. Mutation in gene pps did not affect these properties of B. cenocepacia 370. Mutations in genes lon and pps reduced the virulence of bacteria upon infection of mice.     

Relation between the structural, metabolic and "adhesive" properties of nuclear and cytoplasmic non-ribosomal RNA

Nuclear RNAs release from nucleoproteins of isolated nuclei absorbed on a celite column in a wide range of dissociating conditions (from 1 M LiCl--2 M urea at 2 degrees C to 4 M LiCl--8 M urea at 70-80 degrees C) was demonstrated. Such a high "adhesive" heterogeneity of nuclear RNAs (i.e., variations in the tightness of RNA-protein bonds) appears to be due to the association of nuclear matrix proteins. A direct correlation was found to exist between the metabolic turnover of RNA and the tightness of its association with the nuclear matrix. Actually, the pulse label which rapidly incorporates into the RNAt greater than 50 degrees, the RNA fraction being most tenaciously bound to the matrix, could be chased later into RNAs weakly bound to it. As the RNA-matrix binding weakens, the metabolic and structural properties of a given RNA change, e.g., sedimentation coefficients decrease, while the poly(A)+-RNA content and stability increase. The "adhesive" heterogeneity was found to be inherent in not only nuclear RNAs but also in cytoplasmic non-ribosomal RNAs, showing the same correlation, i.e., the tighter the RNA--protein complex, the higher the rate of RNA turnover. Cytoplasmic RNAs which differ in their adhesiveness may fulfil various intracellular functions, since polyribosomal mRNPs and informosomal mRNPs appear to be enriched in tightly and weakly bound RNA fractions, respectively. The interrelationships between nuclear and cytoplasmic RNAs are discussed.