Changes in the characteristics of human granulo- and monocytopoiesis and the activity of stromal precursor cells in acute hypobaric hypoxia

10 healthy men underwent a 48 hour acute hypobaric hypoxia in the "Taba?" climate chamber imitating conditions of an altitude of 4.00 m. above s.l. The "ascent" and "descent" took 30 minutes each. Blood and bone marrow samples were taken before entering the chamber and immediately after leaving it. A decrease in colony-forming capacity of granulo- and monocyte and fibroblast precursors was shown, along with an increase in functional activity of circulating monocytes and monocyte precursors in bone marrow. A possible role of changes in granulo- and monocytopoiesis and in stromal cells is discussed in relation to the increased morbidity and decreased cicatricial and bone tissue reparation in the mountains.     

Enlarged Similarity of Nucleic Acid Sequences

The concept of nucleic acid sequence base alternations is presented.The number of base alterations for the sequences of differentlength is established. The definition of "enlarged similarity"of nucleic acids sequences on the basis of sequence base alterationsis introduced. Mutual information between sequences is usedas a quantitative measure of enlarged similarity for two comparedsequences. The method of mutual information calculation is developedconsidering the correlation of bases in compared sequences.The definitions of correlated similarity and evolution similaritybetween compared sequences are given. Results of the use ofenlarged similarity approach for DNA sequences analysis arediscussed.     

Pathology of the anterior cingulate cortex in obsessive-compulsive disorder

In this article, the characteristics of the functional activity of the anterior cingulate cortex (ACC), a key element of the neuroanatomical error detection system of the brain in drug-resistant forms of obsessive-compulsive disorder (OCD) are discussed on the basis of both original and published data. Available data indicate the presence of a functional deficit zone in the ACC during PCD. This fact suggests that the functions of the ACC in OCD patients are partially redistributed between other brain areas. Thus, in contrast to the previously accepted ideas, the target of stereotactic surgery for OCD is a pathologically altered brain region. Probably, this explains the fact that the operation does not lead to significant changes in the patient’s psyche. The pathological reorganization of the functional activity of the brain in OCD remains unclear and requires further investigation.     

A comparative study of the effects of Pr<Superscript>3+</Superscript> and La<Superscript>3+</Superscript> ions on calcium dependent processes in frog cardiac muscle and rat heart mitochondria

The inotropic effect of Pr³⁺ and La³⁺ ions on the heart muscle of frog Rana ridibunda, as well as the influence of the ions on respiration, swelling, and the potential (ΔΨ_mito) on the inner membrane of Ca²⁺- loaded rat heart mitochondria, energized by glutamate and malate or succinate in the presence of rotenone were studied. It was found that 2 mM Pr³⁺ in Ringer’s solution reduces the force of spontaneous contractions and those induced by electrical stimulation in the heart; it had a negative chronotropic effect, decreasing the frequency of spontaneous contractions. Pr³⁺ and La³⁺ prevented a decrease in the 2,4-dinitrophenol (DNP)- uncoupled respiration of energized rat heart mitochondria, swelling of these organelles in salt media, and a reduction in ΔΨ_mito on the inner mitochondrial membrane that were induced by Ca²⁺ ions. Retardation by Pr³⁺ and La³⁺ ions of these calcium-induced effects may suggest that in the inner mitochondrial membrane these metals inhibit the opening of the mitochondrial permeability transition pore caused by Ca²⁺ overload of mitochondria. The data we obtained are important for a better understanding of the mechanisms of the damaging action of rare-earth elements on Ca²⁺-dependent processes in the vertebrate myocardium.     

A Database of Potential Reading Frame Shifts in Coding Sequences from Different Eukaryotic Genomes

Biophysics - Abstract—A new data bank containing potential reading frame shifts was developed. A new mathematical method based on the use of the genetic algorithm and dynamic programming was...     

Calcium Is Essential for the Major Pseudopilin in the Type 2 Secretion System

The pseudopilus is a key feature of the type 2 secretion system (T2SS) and is made up of multiple pseudopilins that are similar in fold to the type 4 pilins. However, pilins have disulfide bridges, whereas the major pseudopilins of T2SS do not. A key question is therefore how the pseudopilins, and in particular, the most abundant major pseudopilin, GspG, obtain sufficient stability to perform their function. Crystal structures of Vibrio cholerae, Vibrio vulnificus, and enterohemorrhagic Escherichia coli (EHEC) GspG were elucidated, and all show a calcium ion bound at the same site. Conservation of the calcium ligands fully supports the suggestion that calcium ion binding by the major pseudopilin is essential for the T2SS. Functional studies of GspG with mutated calcium ion-coordinating ligands were performed to investigate this hypothesis and show that in vivo protease secretion by the T2SS is severely impaired. Taking all evidence together, this allows the conclusion that, in complete contrast to the situation in the type 4 pili system homologs, in the T2SS, the major protein component of the central pseudopilus is dependent on calcium ions for activity.In Gram-negative bacteria, the type 2 secretion system (T2SS)² is used for the secretion of several important proteins across the outer membrane (1). The T2SS is also called the terminal branch of the general secretory pathway (Gsp) (2) and, in Vibrio species, the extracellular protein secretion (Eps) apparatus (3). This sophisticated multiprotein machinery spans both the inner and the outer membrane of Gram-negative bacteria and contains 11–15 different proteins. The T2SS consists of three major subassemblies (4–9): (i) the outer membrane complex comprising mainly the crucial multisubunit secretin GspD; (ii) the pseudopilus, which consists of one major and several minor pseudopilins; and (iii) an inner membrane platform, containing the cytoplasmic secretion ATPase GspE and the membrane proteins GspL, GspM, GspC, and GspF.The pseudopilus is a key element of the T2SS that forms a helical fiber spanning the periplasm. The fiber is assembled from multiple subunits of the major pseudopilin GspG (4, 5, 10–14). The pseudopilus is thought to form a plug of the secretin pore in the outer membrane and/or to function as a piston during protein secretion. In recent years, studies of the T2SS pseudopilins led to structure determinations of all individual pseudopilins (13, 15–17). The recent structure of the helical ternary complex of GspK-GspI-GspJ suggested that these three minor pseudopilins form the tip of the pseudopilus (17). A crystal structure of GspG from Klebsiella oxytoca was in a previous study combined with electron microscopy data to arrive at a helical arrangement, with no evidence for special features, such as disulfide bridges, other covalent links, or metal-binding sites, for stabilizing this major pseudopilin or the pseudopilus (13).The pseudopilins of the T2SS share a common fold with the type 4 pilins (15–21). Pilins are proteins incorporated into pili, long appendages on the surface of bacteria forming thin, strong fibers with multiple functions (19, 21). Type 4 pilins and pseudopilins contain a prepilin leader sequence that is cleaved off by a prepilin peptidase, yielding mature protein (10, 11, 22). A distinct feature of the type 4 pilins is the occurrence of a disulfide bridge connecting β4 to a Cys in the so-called “D-region” near the C terminus (21). In a recent study (23) on the thin fibers of Gram-positive bacteria, isopeptide units appeared to be essential for providing these filaments sufficient cohesion and stability. A key question was therefore whether the major pseudopilin GspG also requires a special feature to obtain sufficient stability to perform its function.     

Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria

We studied action of inorganic phosphate (P(i)) on toxic effects of Tl+ in isolated rat liver mitochondria. This is a convenient model to study the toxicity of heavy metals. P(i) markedly retarded contraction of energized mitochondria swollen in the TlNO3 medium and even stronger stimulated swelling and state 4 of succinate-energized mitochondria in the TlNO3 medium. A valinomycin-induced decrease of K+-diffusion potential was also accelerated by Tl+ in the presence of P(i). The mitochondrial permeability transition pore in the medium containing Ca2+, TlNO3, and nitrates of univalent cations was distinctly stimulated by P(i). However, P(i) did not affect both the Tl+-stimulated swelling of nonenergized mitochondria in the TlNO3 medium and swelling of energized mitochondria in the Tl acetate medium. Respiration stimulated by 2,4-dinitrophenol and monoamine oxidase activity of energized mitochondria were not affected by Tl+ regardless of the presence of P(i). We suggested that stimulation by P(i) of toxic action of Tl+ in mitochondria and cells could be due to even greater enhancement of uncoupling of mitochondria as shown by an additional increase of swelling and state 4, and in the greater probability of opening of MPTP in the presence of P(i) and Ca2+.     

Evolutionary Aspects of Cardioprotection

The review addresses the mechanisms of adaptation of the myocardium and cells of the cardiovascular system to hypoxia and ischemia as well as biochemical mechanisms of cardioprotection in animals of different phylogenetic levels. A special focus is placed on general adaptive strategies developed by evolutionarily distant animals in response to hypoxia and ischemia and on preconditioning and myocardial hibernation phenomena.     

The Effects of Thallium on the Spontaneous Contraction of the Heart Muscle and the Energetic Processes in Cardiomyocyte Mitochondria

Biophysics - Abstract—Thallium ions were tested for their effect on the spontaneous contraction of the frog heart muscle and rat heart mitochondria. Tl+ ions reduced all parameters of...