Vol 6, No 1 (2014)

The composition of the intestinal microbiota is regulated by the immune system. This paper discusses the role of cytokines and innate immunity lymphoid cells in the intestinal immune regulation by means of IgA.

Genomic diseases or syndromes with multiple manifestations arise spontaneously and unpredictably as a result of contiguous deletions and duplications generated by unequal recombination in chromosomal regions with a specific architecture. The Williams syndrome is believed to be one of the most attractive models for linking genes, the brain, behavior and cognitive functions. It is a neurogenetic disorder resulting from a 1.5 Mb deletion at 7q11.23 which covers more than 20 genes; the hemizigosity of these genes leads to multiple manifestations, with the behavioral ones comprising three distinct domains: 1) visuo-spatial orientation; 2) verbal and linguistic defect; and 3) hypersocialisation. The shortest observed deletion leads to hemizigosity in only two genes: eln and limk1. Therefore, the first gene is supposed to be responsible for cardiovascular pathology; and the second one, for cognitive pathology. Since cognitive pathology diminishes with a patient’s age, the original idea of the crucial role of genes straightforwardly determining the brain’s morphology and behavior was substituted by ideas of the brain’s plasticity and the necessity of finding epigenetic factors that affect brain development and the functions manifested as behavioral changes. Recently, non-coding microRNAs (miRs) began to be considered as the main players in these epigenetic events. This review tackles the following problems: is it possible to develop relatively simple model systems to analyze the contribution of both a single gene and the consequences of its epigenetic regulation in the formation of the Williams syndrome’s cognitive phenotype? Is it possible to use Drosophila as a simple model system?

While metal nanoparticles are being increasingly used in many sectors of the economy, there is growing interest in the biological and environmental safety of their production. The main methods for nanoparticle production are chemical and physical approaches that are often costly and potentially harmful to the environment. The present review is devoted to the possibility of metal nanoparticle synthesis using plant extracts. This approach has been actively pursued in recent years as an alternative, efficient, inexpensive, and environmentally safe method for producing nanoparticles with specified properties. This review provides a detailed analysis of the various factors affecting the morphology, size, and yield of metal nanoparticles. The main focus is on the role of the natural plant biomolecules involved in the bioreduction of metal salts during the nanoparticle synthesis. Examples of effective use of exogenous biomatrices (peptides, proteins, and viral particles) to obtain nanoparticles in plant extracts are discussed.

Dermal papilla (DP) cells are unique regional stem cells of the skin that induce formation of a hair follicle and its regeneration cycle. DP are multipotent stem cells; therefore we supposed that the efficiency of DPC reprogramming could exceed that of dermal fibroblasts reprogramming. We generated induced pluripotent stem cells from human DP cells using lentiviral transfection with Oct4, Sox2, Klf4, and c-Myc, and cultivation of cells both in a medium supplemented with valproic acid and at a physiological level of oxygen (5%). The efficiency of DP cells reprogramming was ~0.03%, while the efficiency of dermal fibroblast reprogramming under the same conditions was ~0.01%. Therefore, we demonstrated the suitability of DP cells as an alternative source of iPS cells.

Intracellular processing of the antigen encoded by a DNA vaccine is one of the key steps in generating an immune response. Immunization with DNA constructs targeted to the endosomal-lysosomal compartments and to the MHC class II pathway can elicit a strong immune response. Herein, the weakly immunogenic reverse transcriptase of HIV-1 was fused to the minimal lysosomal targeting motif of the human MHC class II invariant chain. The motif fused to the N-terminus shifted the enzyme intracellular localization and accelerated its degradation. Degradation of the chimeric protein occurred predominantly in the lysosomal compartment. BALB/c mice immunized with the plasmid encoding the chimeric protein demonstrated an enhanced immune response, in the form of an increased antigen-specific production of Th1 cytokines, INF-γ and IL-2, by mouse splenocytes. Moreover, the majority of the splenocytes secreted both cytokines; i.e., were polyfunctional. These findings suggest that retargeting of the antigen to the lysosomes enhances the immune response to DNA vaccine candidates with low intrinsic immunogenicity.

Anthrax is a particularly dangerous infectious disease that affects humans and livestock. It is characterized by intoxication, serosanguineous skin lesions, development of lymph nodes and internal organs, and may manifest itsself in either a cutaneous or septic form. The pathogenic agent is Bacillus anthracis, a grampositive, endospore-forming, rod-shaped aerobic bacterium. Efficacious vaccines that can rapidly induce a long-term immune response are required to prevent anthrax infection in humans. In this study, we designed three recombinant human adenovirus serotype-5-based vectors containing various modifications of the fourth domain of the B. anthracis protective antigen (PA). Three PA modifications were constructed: a secretable form (Ad-sPA), a non-secretable form (Ad-cPA), and a form with the protective antigen fused to the Fc fragment of immunoglobulin G2a (Ad-PA-Fc). All these forms exhibited protective properties against Bacillus anthracis. The highest level of protection was induced by the Ad-PA-Fc recombinant adenovirus. Our findings indicate that the introduction of the Fc antibody fragment into the protective antigen significantly improves the protective properties of the Ad-PA-Fc adenovirus against B. anthracis.

Three-dimensional (3D) silk fibroin scaffolds were modified with one of the major bone tissue derivatives (nano-hydroxyapatite) and/or a collagen derivative (gelatin). Adhesion and proliferation of mouse embryonic fibroblasts (MEF) within the scaffold were increased after modification with either nano-hydroxyapatite or gelatin. However, a significant increase in MEF adhesion and proliferation was observed when both additives were introduced into the scaffold. Such modified composite scaffolds provide a new and better platform to study wound healing, bone and other tissue regeneration, as well as artificial organ bioengineering. This system can further be applied to establish experimental models to study cell-substrate interactions, cell migration and other complex processes, which may be difficult to address using the conventional two-dimensional culture systems.

We unveil experimental evidence that put into question the widely held notion concerning the impact of nanoparticles on the bioelectrocatalytic parameters of enzymatic electrodes. Comparative studies of the bioelectrocatalytic properties of fungal bilirubin oxidase from Myrothecium verrucaria adsorbed on gold electrodes, modified with gold nanoparticles of different diameters, clearly indicate that neither the direct electron transfer rate (standard heterogeneous electron transfer rate constants were calculated to be 31±9 s -1) nor the biocatalytic activity of the adsorbed enzyme (bioelectrocatalytic constants were calculated to be 34±11 s -1) depends on the size of the nanoparticles, which had diameters close to or larger than those of the enzyme molecules.