A number of molecules expressed on mammalian cells are involved in the formation of autotolerance. These primarily include CTLA-4/B7 and PD1-PD-L1 signaling pathways. Blockers of these signaling pathways, called checkpoint inhibitors (CPIs) of immunity, are used in the clinic for the treatment of various forms of cancer. Antibodies to CTLA-4 cause systemic toxicity and are approved only for some tumors. Antibodies against PD1 or PD-L1 have been successfully used for the treatment of various forms of cancer and are characterized by low toxicity. However, the response to therapy using CPIs is not always observed. The development of more effective approaches to cancer therapy based on PD1/PD-L1 inhibitors requires additional research. The aim of this work was to express the extracellular part of the murine PD-L1 protein (exPD-L1) and obtain antibodies to PD-L1. The mouse exPD-L1 protein was obtained and characterized in the bacterial expression system. exPD-L1 protein was used to immunize mice in order to produce anti-PD-L1 antibodies. Using hybridomic technology, 5 clones expressing antibodies to exPD-L1 were obtained. Antibodies of the B12 clone were developed in the ascitic fluid of BALB/c mice and purified by affinity chromatography. The ELISA method for purified antibodies showed specific binding to the exPD-L1 protein and the commercial protein of the extracellular part of murine PD-L1. Experiments using flow cytometry and confocal microscopy have shown that the antibodies obtained bind the intracellular form of the PD-L1 protein, unlike commercial antibodies binding the membrane form.

According to WHO, cancer is the cause of ~5 million deaths annually. To date, there is no universal solution to fight cancer despite outstanding achievements of radiotherapy, chemotherapy, and immunotherapy. In this regard, there is a need to develop new approaches to antitumor therapy, in particular based on the search and use of targeted molecules that allow killing tumor cells of various types with high efficiency without significant toxic effects on healthy organs and tissues. This review presents the characteristics of the main proteins of the heat shock proteins (HSP) family, the features of their expression in tumor cells, and the possibility of using monoclonal antibodies against these proteins as a guiding vector for antitumor immunotherapy.

Heat shock proteins of the 70 kDa family (HSP70) are intracellular chaperones necessary for the cell to maintain protein homeostasis. In the cytosol, under normal conditions, these proteins promote the correct folding of proteins, preventing their aggregation, and are involved in protein transport and cell survival. Among the HSP70, there is a pool of stress-inducible proteins Hsp70, which significantly increases in response to a number of stress factors and facilitates cell recovery after stress. Tumor cells, unlike normal, are characterized by the ability to present Hsp70 on the surface of the cell membrane. Membrane-bound Hsp70 can be considered as a danger signal and enhance or inhibit immune responses. A three-dimensional model of cells in the spheroids in varying degrees simulates the structural organization of solid tumors. In cultures of multicellular spheroids (3D), hypoxia and nutrient gradients are formed within the spheroids, which can affect the translocation of Hsp70 to the cell membrane. The purpose of this work was a comparative analysis of Hsp70 expression on tumor cells of various origins when cultivated in a monolayer state (2D) and 3D cultures. Analysis was carried out on breast and pancreatic tumor cell lines, colon and prostate carcinomas, and lymphomas using flow cytometry and confocal microscopy methods. Cultivation in 3D cultures was performed using the antiadhesive PolyHEMA substrate. The results showed that not all carcinomas from our panel express Hsp70 in both 2D and 3D cultures. Some tumor lines have membrane Hsp70 only in 3D cultures. Hsp70 expression was detected on: BT20 breast cancer cells; colon carcinoma SW837; pancreas PANC1; and prostate PC-3. Analysis of Hsp70-positive carcinomas of various localizations in 2D and 3D models may be useful for the application of antibodies against Hsp70 as a vector for the delivery of anticancer drugs.

According to WHO, oncological diseases are the cause of ~5 million people deaths annually. To date, there is no universal solution to fight cancer, despite outstanding achievements in the field of radiotherapy, chemotherapy, and immunotherapy. In this regard, there is a need to develop new approaches to antitumor therapy, in particular based on the search and use of targeted molecules that allow killing tumor cells of various types with high efficiency, without significant toxic effects on healthy organs and tissues. This review presents the characteristics of the main heat shock protein (HSP) families, the features of their expression in tumor cells and the possibility of using monoclonal antibodies to these proteins as a guiding vector for antitumor immunotherapy.

Objective: A number of molecules expressed on mammalian cells are involved in the formation of auto-tolerance. These primarily include CTLA-4/B7 and PD1-PD-L1 signaling pathways. Blockers of these signaling pathways, called checkpoint inhibitors (ICTs) of immunity, are used in the clinic for the treatment of various forms of cancer. Antibodies to CTLA-4 cause systemic toxicity and are approved only for the treatment of melanoma. Antibodies against PD1 or PD-L1 have been successfully used for the treatment of various forms of cancer and are characterized by low toxicity. However, the response to therapy using ICT does not exceed 25–30

For the first time it was shown that the development of resistance to ciprofloxacin in vitro in Acholeplasma laidlawii, a mycoplasma which is widely spread in nature and which is the main contaminant of cell cultures and vaccines, is associated with diverse pathways of virulence evolution: virulome and virulence differ significantly between ciprofloxacin-resistant strains, including those with the same level of antimicrobial resistance.

For the first time it is shown that the development of resistance to melittin in Acholeplasma laidlawii , a mycoplasma that is widely spread in nature and that is the main contaminant of cell cultures and vaccines, is associated with significant changes in the genomic profile, in cellular and vesicular proteomes, as well as in virulence.

A comparative analysis of parental age-associated changes in the reproductive function and embryonic development has been performed for offspring of D. melanogaster imagoes of mutant (w(CS)(1) and w(Or)(1)) and wild-type (Canton-S and Oregon-R) lines. Fruit fly imagoes from three age groups (3-, 10-, and 20-day-old) were used in the experiment. Reciprocal crossings of young (3-day-old) imagoes to individuals from each age group were performed in order to identify the effects of maternal and/or paternal age on reproductive function parameters in the offspring. The effects of maternal and paternal ages on various reproductive function parameters in F-1 offspring were shown to vary between wild-type lines and mutant lines w(CS)(1)and w(Or)(1), which is apparently due to genetic differences between the lines. The white mutation alone or combined with advanced parental age had a negative effect on fertility and viability characteristics in F-1 offspring and caused a predisposition to the development of dominant lethal mutations and death at the pupal stage, such that the emergence of less adapted and viable offspring in the population was prevented.

Drosophila melanogaster serves as an excellent model system to study the control of innate behaviors. Behavior is the ability of animals to change their actions under the influence of internal and external factors, a characteristic feature of the animal type of organization. Sexual behavior of Drosophila is organized as a complex physiological and biochemical trait and consists of certain successive stages, which, as a rule, are repeated several times until mating occurs. These stages include the exchange of visual, sound, and chemosensory signals between the partners. Drosophila white (w) gene, discovered in 1910 by Thomas Hunt Morgan, encodes a subunit of an ATP-binding cassette (ABC) transporter, which loads up pigment granules and deposits the content to pigment cells in the compound eyes. The white gene has housekeeping functions in the central nervous system in addition to its classical role in eye pigmentation. Previously, we have shown the influence of mutant alleles at the white locus on the locomotor activity in Drosophila adults. Therefore, investigating the effect of different white alleles on behavioral traits, including mating behavior, which is also an important component of adaptation, seems to be of interest. The influence of mutant alleles at the white locus on mating behavior characteristics in Drosophila melanogaster imagoes has been studied. Mating activity of males, mating receptivity of females, duration and latency of copulation as traits of mating behavior have been examined. The results of the present study and the analysis of published data have demonstrated that different alleles of white locus, in combination with genetic factors, substantially influence the mating behavior of D. melanogaster. It has been shown that mutant alleles at the white locus play a significant role in controlling the mating behavior of females. Furthermore, it has been found that intensively pigmented individuals are characterized by lower latency of copulation and, as a result, longer mating.

Modern multipurpose Autonomous Underwater Vehicles (AUVs) represent the nextgeneration of robotic systems with new technological tasks faced by researchers. One methodof extending the functionality of the vehicle is installing tunnel thrusters in addition to the sternpropulsion system. Thereby the vehicle becomes able to undertake both survey-style missionsand low speed interactions with the environment. But the efficiency of the tunnel thruster dependsstrongly on the vehicle’s velocity, due to hydrodynamic aspects. The usual solution to this problemuses different control models and thrust allocation methods for these types of mission. A unifiedapproach to thrust allocation is presented in this paper. The approach is based on solving theallocation problem by quadratic programming with variable constraints, depending on the velocityof the AUV and the thrusters’ angle of attack. The well-known implementation of active setmethod was used to model the proposed allocation method.

Influence of age of parents and duration of starvation on egg production and demonstration of embryonic mortality at different stages of egg development has been studied. It is shown that, with increasing age of organisms, the overall egg production reduces and the percentage of embryonic mortality increases at 0–5.5 and 5.5–17 h of development. An increase in the duration of starvation also promotes a reduction in egg production in 3- and 10-day-old adult D. melanogaster compared with short-term starvation. A statistically significant effect of factors, such as the allelic state of the white locus, the genetic background, the age of the parents, and the duration of starvation, on all studied parameters was established.

Male prairie vole preferences for estrous versus diestrous females and associated stimuli were investigated. The role of sexual experience in engendering preferences proved more complex than reported for other species. Naive males did not display preferences. Neither males receiving sexual experience through monogamous cohabitation, nor males housed with two females displayed preferences. Males exposed to both estrous and diestrous females, and males housed with other males and females in a semi-naturalistic setting, displayed preferences. Thus, preferences seem to be "tuned" by experiential manipulations. Cues available for discrimination also influenced the display of preferences, as different results were obtained using apparatus that differed in cue availability. The observed pattern of responsiveness to sex odors may be related to the social organization and mating system of the prairie vole, a mammal that is believed to be monogamous.