Sorption isotherms of metal ions onto an N-(2-sulfoethyl)chitosan-based material from single- and multi-component solutions

The scope of work is to study the mutual influence of metal ions during their sorption by sulfoethylated chitosan. The sorption isotherms of metal ions from single- and multi-component solutions are obtained. The sorption capacity of the sorbent towards Ag(I) and Cu(II) is revealed to be 1.63 and 1.41 mmol/g in single-, and 1.40 and 0.85 mmol/g in five-component solution. By comparing the affinity parameter and capacity of sulfoethylated chitosan towards ions in single- and multi-component solutions, it is concluded that Ag(I) and Cu(II) ions suppress the sorption of cobalt(II), nickel(II), zinc(II), cadmium(II), magnesium(II), calcium(II), strontium(II), barium(II), manganese(II) and lead(II).     

Small RNA F6 Provides Mycobacterium smegmatis Entry into Dormancy

Regulatory small non-coding RNAs play a significant role in bacterial adaptation to changing environmental conditions. Various stresses such as hypoxia and nutrient starvation cause a reduction in the metabolic activity of Mycobacterium smegmatis, leading to entry into dormancy. We investigated the functional role of F6, a small RNA of M. smegmatis, and constructed an F6 deletion strain of M. smegmatis. Using the RNA-seq approach, we demonstrated that gene expression changes that accompany F6 deletion contributed to bacterial resistance against oxidative stress. We also found that F6 directly interacted with 5′-UTR of MSMEG_4640 mRNA encoding RpfE2, a resuscitation-promoting factor, which led to the downregulation of RpfE2 expression. The F6 deletion strain was characterized by the reduced ability to enter into dormancy (non-culturability) in the potassium deficiency model compared to the wild-type strain, indicating that F6 significantly contributes to bacterial adaptation to non-optimal growth conditions.     

Carbenoxolon Is Capable to Regulate the Mitochondrial Permeability Transition Pore Opening in Chronic Alcohol Intoxication

Background: carbenoxolone, which is a derivative of glyceretic acid, is actively used in pharmacology for the treatment of diseases of various etiologies. In addition, we have shown carbenoxolone as an effective inducer of mitochondrial permeability transition pore in rat brain and liver mitochondria. Methods: in the course of this work, comparative studies were carried out on the effect of carbenoxolone on the parameters of mPTP functioning in mitochondria isolated from the liver of control and alcoholic rats. Results: within the framework of this work, it was found that carbenoxolone significantly increased its effect in the liver mitochondria of rats with chronic intoxication. In particular, this was expressed in a reduction in the lag phase, a decrease in the threshold calcium concentration required to open a pore, an acceleration of high-amplitude cyclosporin-sensitive swelling of mitochondria, as well as an increase in the effect of carbenoxolone on the level of mitochondrial membrane-bound proteins. Thus, as a result of the studies carried out, it was shown that carbenoxolone is involved in the development/modulation of alcohol tolerance and dependence in rats.     

Mitochondria-targeted disruptors and inhibitors of cytochrome c/cardiolipin peroxidase complexes: a new strategy in anti-apoptotic drug discovery

The critical role of mitochondria in programmed cell death leads to the design of mitochondriotropic agents as a strategy in regulating apoptosis. For anticancer therapy, stimulation of proapoptotic mitochondrial events in tumor cells and their suppression in surrounding normal cells represents a promising paradigm for new therapies. Different approaches targeting regulation of components of mitochondrial antioxidant system such as Mn-SOD demonstrated significant antitumor efficiency, particularly in combination therapy. This review is focused on a newly discovered early stage of mitochondria-dependent apoptosis - oxidative lipid signaling involving a mitochondria-specific phospholipid cardiolipin (CL). Cytochrome c (cyt c) acts as a CL-specific peroxidase very early in apoptosis. At this stage, the hostile events are still secluded within the mitochondria and do not reach the cytosolic targets. CL oxidation process is required for the release of pro-apoptotic factors into the cytosol. Manipulation of cyt c interactions with CL, inhibition of peroxidase activity, and prevention of CL peroxidation are prime targets for the discovery of anti-apoptotic drugs acting before the "point-of-no-return" in the fulfillment of the cell death program. Therefore, mitochondria-targeted disruptors and inhibitors of cyt c/CL peroxidase complexes and suppression of CL peroxidation represent new strategies in anti-apoptotic drug discovery.     

Suspended nanoporous membranes as interfaces for neuronal biohybrid systems

A biohybrid system composed of neuronal cells and silicon-supported nanoporous membranes has been designed to facilitate control of the biochemical environment of neuronal networks with cellular resolution. The membranes may exhibit variable pore sizes and interpore distances and are interfaced to a microfluidic device. Different porosity parameters give rise to changes in the transconductance of the nanopores and can therefore be used to control diffusion of molecules through the membranes. It was shown that the porous membranes are biocompatible with primary vertebrate as well as insect neurons. Our results indicate that nanoporous membranes may be used to interface with biological materials in a biohybrid system, for example as an artificial chemical synapse interface.     

Explosive-Emission Plasma Dynamics in Ion Diode in Double-Pulse Mode

The results of an experimental investigation of explosive-emission plasma dynamics in an ion diode with self-magnetic insulation are presented. The investigatio...     

Molecular Mechanisms of Skewed X-Chromosome Inactivation in Female Hemophilia Patients—Lessons from Wide Genome Analyses

Introduction: Hemophilia A (HA) is an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency or dysfunction due to F8 gene mutations. HA carriers are usually asymptomatic because their FVIII levels correspond to approximately half of the concentration found in healthy individuals. However, in rare cases, a carrier may exhibit symptoms of moderate to severe HA primarily due to skewed inactivation of her non-hemophilic X chromosome. Aim: The aim of the study was to investigate X-chromosome inactivation (XCI) patterns in HA carriers, with special emphasis on three karyotypically normal HA carriers presenting with moderate to severe HA phenotype due to skewed XCI, in an attempt to elucidate the molecular mechanism underlying skewed XCI in these symptomatic HA carriers. The study was based on the hypothesis that the presence of a pathogenic mutation on the non-hemophilic X chromosome is the cause of extreme inactivation of that X chromosome. Methods: XCI patterns were studied by PCR analysis of the CAG repeat region in the HUMARA gene. HA carriers that demonstrated skewed XCI were further studied by whole-exome sequencing (WES) followed by X chromosome-targeted bioinformatic analysis. Results: All three HA carriers presenting with the moderate to severe HA phenotype due to skewed XCI were found to carry pathogenic mutations on their non-hemophilic X chromosomes. Patient 1 was diagnosed with a frameshift mutation in the PGK1 gene that was associated with familial XCI skewing in three generations. Patient 2 was diagnosed with a missense mutation in the SYTL4 gene that was associated with familial XCI skewing in two generations. Patient 3 was diagnosed with a nonsense mutation in the NKAP gene that was associated with familial XCI skewing in two generations. Conclusion: Our results indicate that the main reason for skewed XCI in our female HA patients was negative selection against cells with a disadvantage caused by an additional deleterious mutation on the silenced X chromosome, thus complicating the phenotype of a monogenic X-linked disease. Based on our study, we are currently offering the X inactivation test to symptomatic hemophilia carriers and plan to expand this approach to symptomatic carriers of other X-linked diseases, which can be further used in pregnancy planning.     

Observation of shear band formation in nanocrystalline Pd–Au alloy during in situ SEM compression testing

Understanding the deformation behavior of nanocrystalline (nc) materials is important because of their possible application as structural materials. The investigation of macroscopic nc samples during in situ mechanical tests can shed light on operating deformation mechanisms. For example, observations during a compression test in a scanning electron microscope (SEM) or results obtained by more localized methods like transmission electron microscopy can extend our knowledge on this subject. In this study, we present the results of in situ SEM compression tests on nc Pd–10 at.% Au alloy with a mean grain size of 23 nm produced using the combination of inert gas condensation with subsequent high-pressure torsion. We show that plastic flow in this material is very inhomogeneous on both the macro and the mesoscale as it is localized in one area of the compression sample and within shear bands. The formation of shear bands is accompanied by strain softening. We propose that such behavior can be explained by the activation of grain boundary mediated deformation mechanisms instead of dislocation-based plasticity. This conclusion was supported by in situ synchrotron XRD measurements which revealed that no preferential grain orientation is forming during the compression of identically prepared samples of the same material.     

Relationship between dissolved organic and inorganic compounds in tributaries of the Lake Baikal

It was shown that the balance between organic and inorganic compounds is mostly conditioned by watershed size and relief, rather than chemistry. The rise and fall of dissolved organic carbon concentration are irreversely proportional to those of acid neutralizing capacity and follow the changes in water flowpaths. This relationship was used to distinguish between dissolved matter sources, and to characterize quantitatively and qualitatively their contribution to surface water chemistry. The proposed approach has restricted applicability to the watersheds composed of sedimentary materials and to the watersheds with high percentage of wetlands. The applicability of the approach is also limited to a variety of environmental conditions. Big watersheds should be divided into lower order subcatchments to reduce uncertainty in interpretation of results. In small and medium watersheds, the proposed approach can be used for predicting water chemistry under different environmental conditions and for tracing contaminants.