Vol 83, No 7 (2018)

Abstract—Here we present new approaches to better understanding multidrug resistance (MDR) development in cancer cells, such as identification of components of a complex process of MDR evolution. Recent advances in the studies of MDR are discussed: 1) chemotherapy agents might be involved in the selection of cancer stem cells resulting in the elevated drug resistance and enhanced tumorigenicity; 2) cell–cell interactions have a great effect on the MDR emergence and evolution; 3) mechanotransduction is an important signaling mechanism in cell–cell interactions; 4) proteins of the ABC transporter family which are often involved in MDR might be transferred between cells via microvesicles (epigenetic MDR regulation); 5) proteins providing cell-to-cell transfer of functional P-glycoprotein (MDR1 protein) via microvesicles have been investigated; 6) P-glycoprotein may serve to regulate apoptosis, as well as transcription and translation of target genes/proteins. Although proving once again that MDR is a complex multi-faceted process, these data open new approaches to overcoming it.

The only pathway for the synthesis of essential amino acids in vertebrates is reversible transamination of their keto analogs with glutamic acid. At the same time, it is commonly accepted that such essential amino acids as lysine and threonine are not involved in transamination and, therefore, cannot be synthesized from their keto analogs. However, using radio-labeled isotopes, synthesis of threonine was demonstrated in rat liver and in a reaction mixture containing chicken liver threonine dehydrogenase. In the review, we discuss why threonine is an essential amino acid in mammals and birds based on the pathways of threonine biosynthesis in these two classes of vertebrates.

Functional disruption and neuronal loss followed by progressive dysfunction of the nervous system underlies the pathogenesis of numerous disorders defined as “neurodegenerative diseases”. Multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system resulting in serious neurological dysfunctions and disability, is one of the most common neurodegenerative diseases. Recent studies suggest that disturbances in mitochondrial functioning are key factors leading to neurodegeneration. In this review, we consider data on mitochondrial dysfunctions in multiple sclerosis, which were obtained both with patients and with animal models. The contemporary data indicate that the axonal degeneration in multiple sclerosis largely results from the activation of Ca²⁺-dependent proteases and from misbalance of ion homeostasis caused by energy deficiency. The genetic studies analyzing association of mitochondrial DNA polymorphic variants in multiple sclerosis suggest the participation of mitochondrial genome variability in the development of this disease, although questions of the involvement of individual genomic variants are far from being resolved.

Type K82 capsular polysaccharide (CPS) was isolated from Acinetobacter baumannii LUH5534. The structure of a linear tetrasaccharide repeating unit of the CPS was established by sugar analysis along with one- and two-dimensional ¹H and ¹³C NMR spectroscopy. Proteins encoded by the KL82 capsule gene cluster in the genome of LUH5534 were assigned to roles in the synthesis of the K82 CPS. In particular, functions were assigned to two new glycosyltransferases (Gtr152 and Gtr153) and a novel pyruvyltransferase, Ptr5, responsible for the synthesis of D-galactose 4,6-(R)-pyruvic acid acetal.

The capacities of relatively nontoxic lipopolysaccharide (LPS) from Rhodobacter capsulatus PG and highly potent LPS from Salmonella enterica serovar Typhimurium to evoke proinflammatory cytokine production have been compared in vivo. Intravenous administration of S. enterica LPS at a relatively low dose (1 mg/kg body weight) led to upregulation of TNF-α, IL-6, and IFN-γ production by non-sensitized CD-1 mice. LPS from R. capsulatus PG used at a four-times higher dose than that from S. enterica elicited production of almost the same amount of systemic TNF-α; therefore, the doses of 4 mg/kg LPS from R. capsulatus PG and 1 mg/kg LPS from S. enterica were considered to be approximately equipotential doses with respect to the LPS-dependent TNF-α production by CD-1 mice. Rhodobacter capsulatus PG LPS was a weaker inducer of the production of TNF-α, IL-6, and IFN-γ, as compared to the equipotential dose of S. enterica LPS. Administration of R. capsulatus PG LPS before S. enterica LPS decreased production of IFN-γ, but not of TNF-α and IL-6, induced by S. enterica LPS. Rhodobacter capsulatus PG LPS also suppressed IFN-γ production induced by S. enterica LPS when R. capsulatus PG LPS had been injected as little as 10 min after S. enterica LPS, but to a much lesser extent. Rhodobacter capsulatus PG LPS did not affect TNF-α and IL-6 production induced by the equipotential dose of S. enterica LPS. In order to draw conclusion on the endotoxic activity of particular LPSs, species-specific structure or arrangement of the animal or human immune systems should be considered.

This is the first report describing the possibility of using a green fluorescent protein chromophore synthetic analog, P-HOBDI-BF₂, as a fluorescent dye for a linear hydrolysis probe used in qPCR. The study was carried out on a system for detection of the plant pathogenic fungus Fusarium avenaceum using a plasmid containing translation elongation factor 1α fragment as a template. To estimate fluorogenic properties of P-HOBDI-BF₂, 6-FAM-and BDP-FL-labeled probes were used. It was demonstrated that a synthetic dye based on the P-HOBDI-BF₂ chromophore can be used for labeling hydrolysis probes for qPCR, but fluorescence increase levels for P-HOBDI-BF₂-labeled probes were slightly lower than those for 6-FAM-labeled ones. At the same time, the sensitivity of P-HOBDI-BF₂-based assays remained high, and this fact together with acceptable fluorescence levels suggests that this dye can be considered as an efficient alternative for reporters traditionally used for fluorescence detection in the FAM channel.

On p. 725 in section Acknowledgments instead of:

This work was supported by the Russian Science Foundation (project No. 14-50-00126) and the Russian Foundation for Basic Research (project No. 13-04-00447).

Should read:

This work was supported by the Russian Science Foundation (project No. 14-50-00126: structural studies, optical and NMR spectroscopy experiments, interpretation of spectra) and the Russian Foundation for Basic Research (project No. 13-04-00447: obtaining biomass of actinobacteria under study, microbiological control, obtaining cell walls and isolation of glycopolymer preparations and their primary chemical analysis).