Ergoreflex: The essence and mechanisms

Physical load increases sympathetic nervous activity, which results in an increased cardiac output, constriction of peripheral vessels, and elevated systemic blood pressure. These changes are outcomes of two mechanisms: the central command from cerebral structures that trigger voluntary movements to activate the vasomotor center and the reflexes initiated by mechanical and metabolic changes in a working muscle. The latter mechanism of the sympathetic system activation is termed ergoreflex. The main effects of ergoreflex on the indices of systemic hemodynamics are the following: activation of mechanosensitive afferents mainly leads to inhibition of the tonic vagal effects on the heart, which explains the rapid increase in heartbeats upon loading; activation of chemosensitive afferents comes with some delay in pace with metabolite accumulation in muscles and leads to an increase in efferent sympathetic activity and a rise in blood pressure. The metabolic reflex effect is particularly high in the case of muscle fatigue. This review deals with the mechanisms underlying the ergoreflex and their adaptation to hypodynamia, physical training, and some pathologies.     

A new approach for study of structural and functional properties of proteins with unknown functions

Selected proteins were produced in Escherichia coli bacterial expression system--three proteins from extremophil bacteria: a putative monooxygenase from Deinococcus radiodurans, a putative nucleotidyltransferase from Thermotoga maritima, a putative oxidoreductase from Exiguobacterium sibiricum; and a shaperon from Homo sapiens DJ-1. The protocol of isolation & purification of recombinant proteins were developed that allowed to obtain expression products with the purity of no less than 96%. Conditions for the crystallization have been selected that allowed a stable growth of crystals. Preliminary x-ray experiments were conducted in order to confirm the quality of produced crystals; the resolution of obtained structural data was from 1.2 to 1.8 angstrom.     

Diagnostic system for studying generation of subterahertz radiation during beam-plasma interaction in the GOL-3 facility

The design principles and construction of the subterahertz radiometric spectral systems developed for the GOL-3 facility are described. The spectral systems are designed according to the quasi-optical scheme and use multilayer filters based on frequency-selective surfaces. The design and manufacturing technology of such elements are discussed. The results of measuring subterahertz radiation of plasma at the frequency close to the double plasma frequency are presented.     

Efficient and specific rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like ubiquitin ligase

To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and LYPx(n)L late assembly (L) domains. In contrast, less-complex retroviruses often use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically active HECT domain and was specific, since other Nedd4 family proteins showed little activity and an unrelated retrovirus was not rescued. The residual C2 domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the association of Nedd4-2s with Gag, as reflected by its incorporation into virus-like particles. Interestingly, the incorporation of Nedd4-2s also depended on its active site, indicating that the ability to form a thioester with ubiquitin was required. These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery.     

VHL inactivation in sporadic clear cell renal carcinoma

Clear cell renal carcinoma (CCRC) accounts for 75% of all renal cancer cases. The majority of CCRCs displays inactivation of the VHL suppressor gene as a result of mutations, allelic deletions, and/or methylation. Data on the effect of VHL inactivation on the prognosis in CCRC are discrepant. Comprehensive molecular genetic analysis of VHL was performed for 64 CCRCs: mutations were identified by single strand conformation polymorphism analysis and subsequent sequencing, a loss of heterozygosity was studied with two STR markers, and methylation was assessed by methylation-sensitive PCR. In total, 17 somatic mutations, including 12 new ones, were found in VHL. Allelic deletions of VHL were detected in 31.6% of cases; methylation was observed in 7.8% of cases. In total, VHL was inactivated in 46.9% of CCRC cases and in 51.7% of patients with CCRC stage I. The frequencies of mutations, loss of heterozygosity, and methylation did not correlate with clinical features of CCRC or pathological characteristics of the tumor. Studies of the molecular genetics alterations of VHL are thought to facilitate the identification of diagnostic and prognostic markers of renal cancer, e.g., the selection of an optimal panel of methylated suppressor genes.     

Separation and characterization of deoxyribonucleases from hepatopancreas of freshwater snail in normality and under in vivo model intoxication

Deoxyribonucleases (DNases) differing in the subcellular localization and specificity towards native and denatured substrates and in products of cleavage of endogenous DNA were isolated for the first time from the hepatopancreas of freshwater snail by differential sedimentation and preparative isoelectrofocusing. It was defined found that treatment with phenol leads to activatesion of the most of the investigated DNases, especially in lysosomes, and induces two new DNases of lysosomal origin. The possible different participation of certain DNases of the snail hepatopancreas in the regulation of DNA degradation under intoxication is discussed.     

Chemical composition of the sponge Chondrosia reniformis from [2pt] the Canary Islands

Lake Zempoala was studied throughout 16 months in 1996–1997. It is a shallow monomictic lake situated at 2800 masl at the Neovolcanic Belt, well within the Mexican tropical zone. Most of the phytoplankton species in this lake may be characterized as temperate, according to their geographical distribution. A break down in phytoplankton biomass was observed before the lake's circulation, and open to question if a clear-water phase could be present in a tropical lake.     

Secreted Bacillus anthracis proteases target the host fibrinolytic system

The fibrinolytic system is often the target for pathogenic bacteria, resulting in increased fibrinolysis, bacterial dissemination, and inflammation. The purpose of this study was to explore whether proteases NprB and InhA secreted by Bacillus anthracis could activate the host's fibrinolytic system. NprB efficiently activated human pro-urokinase plasminogen activator (pro-uPA), a key protein in the fibrinolytic cascade. Conversely, InhA had little effect on pro-uPA. Plasminogen activator inhibitors (PAI)-1, 2 and the uPA receptor were also targets for NprB in vitro. InhA efficiently degraded the thrombin-activatable fibrinolysis inhibitor (TAFI) in vitro. Mice infected with B. anthracis showed a significant decrease in blood TAFI levels. In another mouse experiment, animals infected with isogenic inhA deletion mutants restored TAFI levels, while the levels in the parent strain decreased. We propose that NprB and InhA may contribute to the activation of the fibrinolytic system in anthrax infection.