Composite structure of vortices in two-component Bose-Einstein condensate

In contrast to one-component Bose-Einstein condensate case, the vortices in two-component condensate can have various complicated structures. The vortices in a space-homogeneous Bose-Einstein condensate have been studied in this paper. It is shown that the vortex structure is described by three dimensionless parameters. This is totally different from the usual one-component condensate case, where an isolated vortex is described by a parameter-less dimensionless equation. The two-component vortex structure strongly depends on the sign of "interaction" constant of the components. A few types of vortices with different qualitative structure are explored. We show that the super-density vortices can exist, when the "interaction" constant is positive. The super-density vortices have the near-axis density greater than the equilibrium density of a homogeneous space Bose-Einstein condensate. We also show that the vortices with opposite direction of the condensate component rotation near the axis and far off the axis can exist.Comment: LaTeX, 13 pages, 4 figures, UJP styl

Hemoglobin is an oxygen-dependent glutathione buffer adapting the intracellular reduced glutathione levels to oxygen availability

Fast changes in environmental oxygen availability translate into shifts in mitochondrial free radical production. An increase in intraerythrocytic reduced glutathione (GSH) during deoxygenation would support the detoxification of exogenous oxidants released into the circulation from hypoxic peripheral tissues. Although reported, the mechanism behind this acute oxygen-dependent regulation of GSH in red blood cells remains unknown. This study explores the role of hemoglobin (Hb) in the oxygen-dependent modulation of GSH levels in red blood cells. We have demonstrated that a decrease in Hb O2 saturation to 50% or less observed in healthy humans while at high altitude, or in red blood cell suspensions results in rising of the intraerythrocytic GSH level that is proportional to the reduction in Hb O2 saturation. This effect was not caused by the stimulation of GSH de novo synthesis or its release during deglutathionylation of Hb's cysteines. Using isothermal titration calorimetry and in silico modeling, we observed the non-covalent binding of four molecules of GSH to oxy-Hb and the release of two of them upon deoxygenation. Localization of the GSH binding sites within the Hb molecule was identified. Oxygen-dependent binding of GSH to oxy-Hb and its release upon deoxygenation occurred reciprocally to the binding and release of 2,3-bisphosphoglycerate. Furthermore, noncovalent binding of GSH to Hb moderately increased Hb oxygen affinity. Taken together, our findings have identified an adaptive mechanism by which red blood cells may provide an advanced antioxidant defense to respond to oxidative challenges immediately upon deoxygenation

Development of Peptide Biopharmaceuticals in Russia

Peptides are low-molecular-weight substances that participate in numerous important physiological functions, such as human growth and development, stress, regulation of the emotional state, sexual behavior, and immune responses. Their mechanisms of action are based on receptor–ligand interactions, which result in highly selective effects. These properties and low toxicity enable them to be considered potent drugs. Peptide preparations became possible at the beginning of the 20th century after a method was developed for selectively synthesizing peptides; however, after synthesis of the first peptide drugs, several issues related to increasing the stability, bioavailability, half-life, and ability to move across cell membranes remain unresolved. Here, we briefly review the history of peptide production and development in the biochemical industry and outline potential areas of peptide biopharmaceutical applications and modern approaches for creating pharmaceuticals based on synthetic peptides and their analogs. We also focus on original peptide drugs and the approaches used for their development by the Russian Federation

Development of Peptide Biopharmaceuticals in Russia

Peptides are low-molecular-weight substances that participate in numerous important physiological functions, such as human growth and development, stress, regulation of the emotional state, sexual behavior, and immune responses. Their mechanisms of action are based on receptor–ligand interactions, which result in highly selective effects. These properties and low toxicity enable them to be considered potent drugs. Peptide preparations became possible at the beginning of the 20th century after a method was developed for selectively synthesizing peptides; however, after synthesis of the first peptide drugs, several issues related to increasing the stability, bioavailability, half-life, and ability to move across cell membranes remain unresolved. Here, we briefly review the history of peptide production and development in the biochemical industry and outline potential areas of peptide biopharmaceutical applications and modern approaches for creating pharmaceuticals based on synthetic peptides and their analogs. We also focus on original peptide drugs and the approaches used for their development by the Russian Federation

Basal Glutathionylation of Na,K-ATPase α-Subunit Depends on Redox Status of Cells during the Enzyme Biosynthesis

Many viruses induce oxidative stress and cause S-glutathionylation of Cys residues of the host and viral proteins. Changes in cell functioning during viral infection may be associated with glutathionylation of a number of key proteins including Na,K-ATPase which creates a gradient of sodium and potassium ions. It was found that Na,K-ATPase α-subunit has a basal glutathionylation which is not abrogated by reducing agent. We have shown that acute hypoxia leads to increase of total glutathionylation level of Na,K-ATPase α-subunit; however, basal glutathionylation of α-subunit increases under prolonged hypoxia only. The role of basal glutathionylation in Na,K-ATPase function remains unclear. Understanding significance of basal glutathionylation is complicated by the fact that there are no X-ray structures of Na,K-ATPase with the identified glutathione molecules. We have analyzed all X-ray structures of the Na,K-ATPase α-subunit from pig kidney and found that there are a number of isolated cavities with unresolved electron density close to the relevant cysteine residues. Analysis of the structures showed that this unresolved density in the structure can be occupied by glutathione associated with cysteine residues. Here, we discuss the role of basal glutathionylation of Na,K-ATPase α-subunit and provide evidence supporting the view that this modification is cotranslational

Depth of the Steroid Core Location Determines the Mode of Na,K-ATPase Inhibition by Cardiotonic Steroids

Cardiotonic steroids (CTSs) are specific inhibitors of Na,K-ATPase (NKA). They induce diverse physiological effects and were investigated as potential drugs in heart diseases, hypertension, neuroinflammation, antiviral and cancer therapy. Here, we compared the inhibition mode and binding of CTSs, such as ouabain, digoxin and marinobufagenin to NKA from pig and rat kidneys, containing CTSs-sensitive (α1S) and -resistant (α1R) α1-subunit, respectively. Marinobufagenin in contrast to ouabain and digoxin interacted with α1S-NKA reversibly, and its binding constant was reduced due to the decrease in the deepening in the CTSs-binding site and a lower number of contacts between the site and the inhibitor. The formation of a hydrogen bond between Arg111 and Asp122 in α1R-NKA induced the reduction in CTSs’ steroid core deepening that led to the reversible inhibition of α1R-NKA by ouabain and digoxin and the absence of marinobufagenin’s effect on α1R-NKA activity. Our results elucidate that the difference in signaling, and cytotoxic effects of CTSs may be due to the distinction in the deepening of CTSs into the binding side that, in turn, is a result of a bent-in inhibitor steroid core (marinobufagenin in α1S-NKA) or the change of the width of CTSs-binding cavity (all CTSs in α1R-NKA)

Hemoglobin is an oxygen-dependent glutathione buffer adapting the intracellular reduced glutathione levels to oxygen availability

Fast changes in environmental oxygen availability translate into shifts in mitochondrial free radical production. An increase in intraerythrocytic reduced glutathione (GSH) during deoxygenation would support the detoxification of exogenous oxidants released into the circulation from hypoxic peripheral tissues. Although reported, the mechanism behind this acute oxygen-dependent regulation of GSH in red blood cells remains unknown.This study explores the role of hemoglobin (Hb) in the oxygen-dependent modulation of GSH levels in red blood cells. We have demonstrated that a decrease in Hb O2 saturation to 50% or less observed in healthy humans while at high altitude, or in red blood cell suspensions results in rising of the intraerythrocytic GSH level that is proportional to the reduction in Hb O2 saturation. This effect was not caused by the stimulation of GSH de novo synthesis or its release during deglutathionylation of Hb's cysteines. Using isothermal titration calorimetry and in silico modeling, we observed the non-covalent binding of four molecules of GSH to oxy-Hb and the release of two of them upon deoxygenation. Localization of the GSH binding sites within the Hb molecule was identified. Oxygen-dependent binding of GSH to oxy-Hb and its release upon deoxygenation occurred reciprocally to the binding and release of 2,3-bisphosphoglycerate. Furthermore, noncovalent binding of GSH to Hb moderately increased Hb oxygen affinity. Taken together, our findings have identified an adaptive mechanism by which red blood cells may provide an advanced antioxidant defense to respond to oxidative challenges immediately upon deoxygenation

Plasma Cytokines Level and Spinal Cord MRI Predict Clinical Outcome in a Rat Glial Scar Cryoinjury Model

Traumatic injury of the spinal cord is still one of the most challenging problems in the neurosurgical practice. Despite a long history of implementation of translational medicine in the field of spinal cord injury (SCI), it remains one of the most frequent causes of human disability and a critical situation for world healthcare systems. Here, we used our rat model of the of unilateral controlled SCI induced by a cryoinjury, which consistently reproduces glial scarring and posttraumatic cyst formation, and specifically evaluated histological, bioimaging and cytokine data. We propose a 10-grade scoring scale, which can objectively estimate the extent of damage of the experimental SCI according to the magnetic resonance imaging (MRI) results. It provides a homogeneous and reliable visual control of the dynamics of the posttraumatic processes, which makes it possible to clearly distinguish the extent of early damage, the formation of glial scars and the development of posttraumatic syringomyelic cysts. The concentration of cytokines and chemokines in the plasma following the experimental SCI increased up to two orders of magnitude in comparison with intact animals, suggesting that a traumatic injury of the spinal cord was accompanied by a remarkable cytokine storm. Our data suggested that the levels of IL-1α, IL-1β, TNFα, GRO/KC, G-CSF, IFNγ and IL-13 may be considered as a reliable prognostic index for SCI. Finally, we demonstrated that MRI together with plasma cytokines level directly correlated and reliably predicted the clinical outcome following SCI. The present study brings novel noninvasive and intravital methods for the evaluation of the therapeutic efficacy of SCI treatment protocols, which may be easily translated into the clinical practice