Death receptors: New opportunities in cancer therapy

© 2017 Park-media, Ltd. This article offers a detailed review of the current approaches to anticancer therapy that target the death receptors of malignant cells. Here, we provide a comprehensive overview of the structure and function of death receptors and their ligands, describe the current and latest trends in the development of death receptor agonists, and perform their comparative analysis. In addition, we discuss the DR4 and DR5 agonistic antibodies that are being evaluated at various stages of clinical trials. Finally, we conclude by stating that death receptor agonists may be improved through increasing their stability, solubility, and elimination half-life, as well as by overcoming the resistance of tumor cells. What's more, effective application of these antibodies requires a more detailed study of their use in combination with other anticancer agents

Deimination of the myelin basic protein decelerates its proteasome-mediated metabolism

© 2016, Pleiades Publishing, Ltd.Deimination of myelin basic protein (MBP) by peptidylarginine deiminase (PAD) prevents its binding to the proteasome and decelerates its degradation by the proteasome in mammalian cells. Potential anticancer drug tetrazole analogue of chloramidine 2, at concentrations greater than 1 µM inhibits the enzymatic activity of PAD in vitro. The observed acceleration of proteasome hydrolysis of MBP to antigenic peptides in the presence of PAD inhibitor may increase the efficiency of lesion of the central nervous system by cytotoxic lymphocytes in multiple sclerosis. We therefore suggest that clinical trials and the introduction of PAD inhibitors in clinical practice for the treatment of malignant neoplasms should be performed only after a careful analysis of their potential effect on the induction of autoimmune neurodegeneration processes

Effects of the Blp1 locus, which controls melanin accumulation in the barley ear, on the size and weight of seeds

Background. In cereals, photosynthetically active parts of the ear significantly contribute to seed size and weight at the grain-filling stage. In barley, ear tissues may accumulate melanin pigments synthesized in chloroplast-derived melanoplasts. Effects of such pigments on yield parameters of seeds have not been evaluated to date.Materials and methods. Seed weight and size assessed by image analysis were compared between two near-isogenic barley lines differing in alleles of the Blp1 gene, which determines melanin accumulation in ear tissues. Data on grainrelated parameters were collected during 6 years and include data on seeds grown either in the field or under greenhouse conditions.Results and discussion. A negative effect of the Blp1 locus on the weight of 1000 seeds harvested in the field but not in the greenhouse was revealed. To determine whether this effect is related to grain size, a comparison of two-dimensional linear parameters of seeds between the lines was performed. It was shown that unlike the length and the area of seeds, the width of seeds was also negatively affected by the Blp1 locus. Although the same factors affected the weight of 1000 seeds and the width of seeds, a correlation between them was not found, implying a dependence of seed weight on other factors such as thickness and its related parameter, seed volume.Conclusion. Effects of barely ear pigmentation and of the gene controlling it on yield-related parameters of seeds were studied here for the first time. The observed negative impact of the Blp1 locus on seed weight and size may be mediated by an interfering chloroplast activity and/or accumulation of assimilates via melanogenesis. Additional studies are necessary to test this supposition and to investigate the interaction of melanin synthesis and photosynthetic activity of the tissues accumulating this pigment

Structural and functional divergence of homoeologous genes in allopolyploid plant genomes

Allopolyploid organisms can be formed by hybridization between closely related plant species with similar genomes. It is believed that many plant species have passed through allopolyploidization, which played a significant role in the formation of a huge diversity of plants, as well as their high adaptive capacity. Thanks to the whole genome sequencing of a wide range of angiosperm species and comparative analysis of genome structure, the sequence of events that formed the genomes of modern plant taxa was restored. These studies have shown that many diploid species have passed through more than one cycle of polyploidization-diploidization. The purpose of this review is to summarize the estimates of what proportion of genes is undergoing changes due to allopoly-ploidization and to illustrate the variety of mechanisms underlying the functional divergence of homoeologous copies (orthologous genes in allopolyploid subgenomes). Changes of individual copies can be associated with epigenetic features of the gene organization (the methylation status of the promoter region or the presence of copy-specific small interfering RNA) or can affect structure of the coding or regulatory regions of the gene. Studies on artificial allopolyploid plants showed widespread transcriptional dominance and change of the transcription level as compared with the genes of diploid parental forms. The study of the transcription of certain homoeologous gene copies allowed estimating the extent of the complete suppression of certain homoeologous genes in newly synthesized (0.4–5.0 %) and natural (30 %) allopolyploids. One the whole, full or partial suppression affects up to 49% of the wheat genes

Myelin-Reactive Monoclonal Antibodies from Multiple Sclerosis Patients Cross-React with Nucleoproteins in HEp-2 Lysate

© 2016, Springer Science+Business Media New York.Autoimmune disorders are characterized by appearance of self-reactive species of immune system such as T cells, B cells and antibodies. For the majority of autoimmune pathologies the list of specific autoantigens is known. Myelin basic protein (MBP) is one of the most important autoantigens in multiple sclerosis (MS), which destruction is a hallmark of disease progression. Antibodies toward MBP are found in serum and cerebrospinal fluid of MS patients. Here we investigated whether monoclonal human MBP-specific antibodies selected from MS patients repertoire cross-react with other autoimmune markers. For this purpose we performed Western blot analysis of recombinant anti-MBP antibodies with HEp-2 cell lysate. Our data suggest existence of enhanced level of cross-reactivity of anti-MBP antibodies with ribonucleoprotein A (RNP A), a marker of Sharp’s syndrome and systemic lupus erythematosus, ribosomal P protein (Rib. P-Prot), a marker for systemic lupus erythematosus, and centromere protein A/B (CENP A/B), markers for progressive systemic sclerosis

Studying grain color diversity in the barley collection of VIR

Background. Dark color of barley grain (Hordeum vulgare L.) can be caused by the synthesis and accumulation of two types of polyphenolic pigments – anthocyanins and melanins, which perform important functions in plant life, participating in the regulation of growth and development, and protecting plants from adverse environmental conditions. The aim of this study was to investigate the diversity of barley in the VIR collection in the context of grain color.Materials and methods. To analyze the pigment composition of the grain, 150 barley accessions with colored grains were selected from the VIR collection. Anthocyanins and melanins in grain husk were identified using qualitative reactions.Results and discussion. It was shown that in 60% of the accessions the dark color of their grain was induced by independent accumulation of melanin, while the accessions characterized by accumulation of only anthocyanins, and those with combined accumulation of anthocyanins and melanins, were 14.6% and 14%, respectively. For 11.3% of the accessions the presence of anthocyanins and melanins in grain husk was not found; their pigmentation could presumably be associated with an increased content of other polyphenolic pigments – proanthocyanidins. Accessions with melanin in grain predominated in all identified geographic groups, while other types of pigmentation were most evenly represented in the regions with the widest genetic diversity of barleys – Africa, East Asia, and the Middle East.Conclusion. Dark pigmentation of barley grain was shown to be mainly associated with the accumulation of melanin, and this type of pigmentation prevails in all geographical regions identified. The results obtained made it possible to describe the barley collection more fully and expand the possibilities of its utilization

Features of innovative personnel management of service companies in the period of implementation of organizational changes

© Authors. In the conditions of development and improvement of management systems in organizations of the service sector, the requirements to the quality of labor and the qualification of personnel are increasing, which is an essential condition for achieving competitive advantages. The relevance of the research of the features of innovative personnel management in the service sector is determined by the growing role of this industry in the modern economy. Based on the use of theoretical and empirical methods, conditions and mechanisms for the formation of an innovative system of training/development of personnel at service enterprises were identified. The paper substantiates the priority tasks of personnel management in the context of the basic concepts of organizational change. As a result of the study, a program to improve the skills and trainings for employees of service enterprises, taking into account the characteristics of their work activities, was developed. An author's two-component model for estimating investment in human capital is proposed, which reflects the personal development of employees

Administration of Myelin Basic Protein Peptides Encapsulated in Mannosylated Liposomes Normalizes Level of Serum TNF- α and IL-2 and Chemoattractants CCL2 and CCL4 in Multiple Sclerosis Patients

© 2016 Yakov Lomakin et al.We have previously shown that immunodominant MBP peptides encapsulated in mannosylated liposomes (Xemys) effectively suppressed experimental allergic encephalomyelitis (EAE). Within the frames of the successfully completed phase I clinical trial, we investigated changes in the serum cytokine profile after Xemys administration in MS patients. We observed a statistically significant decrease of MCP-1/CCL2, MIP-1β/CCL4, IL-7, and IL-2 at the time of study completion. In contrast, the serum levels of TNF-α were remarkably elevated. Our data suggest that the administration of Xemys leads to a normalization of cytokine status in MS patients to values commonly reported for healthy subjects. These data are an important contribution for the upcoming Xemys clinical trials

mRNA expression profile of mouse oligodendrocytes in inflammatory conditions

© 2016, Pleiades Publishing, Ltd.In this study, we performed transcriptome profiling of oligodendrocyte culture of mice treated with the remyelinating therapeutic agent benztropine in the presence and absence of interferon gamma (IFNγ). The results of this work are important for understanding the expression profile of oligodendrocytes under conditions of systemic inflammation in the central nervous system in multiple sclerosis as well as the mechanisms of cellular response to benztropine in light of its possible use for the treatment of multiple sclerosis

Specificity of Growth and Synthesis of Secondary Metabolites in Cultures in vitro Digitalis lanata Ehrh.

Abstract: Rhizogenic, callus, and suspension cultures in vitro were obtained for Digitalis lanata and their growth, cytophysiological and biochemical characteristics were investigated. The obtained cultures were characterized by good growth characteristics (growth indexes I in the range of 5–13). Suspension cell culture had a specific growth rate μ within 0.2–0.3 days–1 and it was characterized by a two-phase growth curve (growth retardation during the exponential phase). In the obtained cultures, a study of the qualitative and quantitative composition of secondary metabolites by UPLC-ESI-MS and HPLC-ESI-MS showed the absence of cardiac glycosides. At the same time, phenylethanoids and steroidal glycosides of the furostanol type were found in all studied cultures. The total content of phenylethanoids in callus and suspension cultures was approximately 0.5% of the dry biomass. Based on the results of mass spectrometry, ten phenylethanoid structures, including digiciliside A, digiciliside B, maxoside, purpureaside E, and their methyl derivatives and isomers, and also seven furostanol glycosides with aglycones tigogenin and gitogenin were identified. It has been shown that the composition of secondary metabolites depends on the degree of cell differentiation: furostanol glycosides were prevalent in a rhizogenic culture consisting mainly of differentiated cells, while the diversity of phenylethanoids significantly increases in callus and suspension cell cultures consisting of dedifferentiated cells. The results of the study confirm the hypothesis put forward in our previous works about the specificity of secondary metabolism and its high intensity in plant cell cultures. © 2022, The Author(s).Government Council on Grants, Russian Federation: 075-15-2019-1882The work was carried out on the basis of the “Scientific and Production Biotechnological Complex for the Study, Preservation, and Practical Application of Cultured Cells and Organs of Higher Plants and Microalgae” with the financial support of the Megagrant of the Government of the Russian Federation (Agreement no. 075-15-2019-1882)