Applying bioinformatics for antibody epitope prediction using affinity-selected mimotopes – relevance for vaccine design

To properly characterize protective polyclonal antibody responses, it is necessary to examine epitope specificity. Most antibody epitopes are conformational in nature and, thus, cannot be identified using synthetic linear peptides. Cyclic peptides can function as mimetics of conformational epitopes (termed mimotopes), thereby providing targets, which can be selected by immunoaffinity purification. However, the management of large collections of random cyclic peptides is cumbersome. Filamentous bacteriophage provides a useful scaffold for the expression of random peptides (termed phage display) facilitating both the production and manipulation of complex peptide libraries. Immunoaffinity selection of phage displaying random cyclic peptides is an effective strategy for isolating mimotopes with specificity for a given antiserum. Further epitope prediction based on mimotope sequence is not trivial since mimotopes generally display only small homologies with the target protein. Large numbers of unique mimotopes are required to provide sufficient sequence coverage to elucidate the target epitope. We have developed a method based on pattern recognition theory to deal with the complexity of large collections of conformational mimotopes. The analysis consists of two phases: 1) The learning phase where a large collection of epitope-specific mimotopes is analyzed to identify epitope specific “signs” and 2) The identification phase where immunoaffinity-selected mimotopes are interrogated for the presence of the epitope specific “signs” and assigned to specific epitopes. We are currently using computational methods to define epitope “signs” without the need for prior knowledge of specific mimotopes. This technology provides an important tool for characterizing the breadth of antibody specificities within polyclonal antisera

Cognitive Coherence as the Element of Functional Valence in COVID-19 Terminological System

Background. The relevance of the study is predetermined by the uniqueness of the communicative and discursive field formed during COVID-19 pandemic. The manifestation of COVID-19-related nominative categories occurs spontaneously and depends on pragmatic motives of social interaction at the global international level. The atypicality of COVID-19 terminological system development sets up the research course directed at both the process of diffuse terminological conglomerate formation and its conceptualization based on the mechanisms of cognitive activity implementation viewed through the cultural specificity revealed at the level of terminological functioning and terminological systemic unity. Objective. This article presents the results of a corpus-based research of cognitive and discursive features of COVID-19 terminological system development. Methods. The research material is a sample of Russian and English media texts selected via automatized algorithms of data parsing. Media discourse reflects short-term socially significant fluctuations in global information agenda directly related to semantic shifts in COVID-19 representation that are revealed through the variety of linguistic and extralinguistic discursive means and compared within the linguo-cultural communities under study. Results. As a result of content analysis and subsequent component analysis the peculiarities of COVID-19 terminological system development appear to be predetermined by the parallel structuring and transformation of COVID-19 semantic representation formed in the temporal perspective of pandemic waves on the basis of fundamental mechanisms of cognitive activity. The functional valence of COVID-19 terminological system is explicated through the convergence of cognitive components that result in terminological coherence and gradual formation of the denotative component of meaning through cognitive compilation of occasional semic characteristics. Conclusion. Cognitive coherence as the element of COVID-19 terminological system functional valence contributes to its gradual structuring and determines the features of semantic arrangement of COVID-19 conceptual field

Variability of pathogenicity factors representative of the human microbiome under the influence of γ-Fe2O3 nanoparticles

Biomedical applications of nanoparticles require deep understanding of their interaction with normal human microflora. Previously, the toxic and mutagenic properties of iron oxide nanoparticles as well as their effect on the growth and morphology of the microflora were extensively investigated. However, the studies related to the variability of microbial pathogenicity factors induced by iron oxide nanoparticles are very limited. Meanwhile, this characteristic of microbes is genetically determined and is important for their survival and distribution in the human body. Therefore, pathogenicity factors are significant indicators of the experimental studies. In this work, the effect of the presence of Fe2O3 nanoparticles obtained by laser target evaporation (LTE) on selected enzymes that demonstrate invasion and aggression factors was evaluated for three reference strains of Candida albicans, Staphylococcus aureus, and Escherichia coli. It was found that the presence of LTE Fe2O3 nanoparticles supplied in the form of water-based suspensions does not induce changes of the above-mentioned parameters

Characterizing Complex Polysera Produced by Antigen-Specific Immunization through the Use of Affinity-Selected Mimotopes

BACKGROUND: Antigen-based (as opposed to whole organism) vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity. METHODOLOGY/PRINCIPAL FINDINGS: Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes) can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets. CONCLUSIONS/SIGNIFICANCE: By combining our novel strategy with existing methods of epitope prediction based on physical properties of an individual protein, we believe that this method offers a robust method for characterizing the breadth of epitope-specificity within a specific polyserum. This strategy is useful as a tool for monitoring immunity following vaccination and can also be used to define relevant epitopes for the creation of novel vaccines

Клиническое обоснование применения стволовых клеток в лечении рецессии десны

The aim of the study is to improve the results of complex treatment of patients with gingival recession on the basis of validation of new, highly effective methods using autologous mesenchymal stem cells. A complex treatment was conducted in 93 patients with an anatomical recession of the gum in combination with dentoalveolar anomalies at the age of 20 to 29 years. Patients were divided into 3 groups depending on the treatment used. All patients underwent periodontological treatment. In the 2nd group, patients underwent periodontological treatment including orthodontic equipment, in the 3rd group, they underwent orthodontic treatment, and a cell transplant based on a mixture of autologous mesenchymal stem cells and sterile bioplastic collagen material “Collost” was used. A comprehensive assessment of the periodontal tissue of the three groups showed that among the patients who received the standard treatment complex, a good condition of the periodontal tissues in 1 to 2 years after treatment was noted only in 16.7 % of the patients of the 1st group. Inclusion of orthodontic treatment made it possible to obtain good results in 25 % of patients in the 2nd group, which is 8 % more than in the 1st group. At the same time, good treatment results were revealed in 94 % of the 3rd group patients, who underwent periodontological and orthodontic treatment using autologous mesenchymal stem cells, which confirms the need for measures aimed to normalize the position of teeth, dentition and bite with the use of small orthodontic long-acting forces, to improve the microcirculation of periodontal tissues, and to restore the contour of marginal dreams. Inclusion of autologous mesenchymal stem cells in the complex treatment of patients with gingival recession is accompanied by a 1.6-fold decrease in the prevalence and gum recession (1.15 mm), and a 2.6-fold increase in the tissue volume, by the stimulation of periodontal microcirculation processes (the capillary periodontal pressure is increased by a factor of 1.1 time and the intensity of periodontic microcirculation is increased by a factor of 3.1 times), as well as by the normalization of the position of teeth, dentition and occlusion, which allowed one to obtain good long-term results in 94 % of patients.Цель исследования – улучшить результаты лечения пациентов с рецессией десны на основе научного обоснования применения нового высокоэффективного метода с использованием аутологичных мезенхимальных стволовых клеток. Проведено комплексное лечение у 93 пациентов с анатомической рецессией десны в сочетании с зубочелюстными аномалиями в возрасте 20–29 лет. Пациентов распределили на 3 группы в зависимости от примененного лечения. Всем пациентам проводили периодонтологическое лечение. Во 2-й группе пациентам наряду с периодонтологическим лечением включили ортодонтическую аппаратуру, в 3-й группе использовали ортодонтическое лечение и применение клеточного трансплантата на основе смеси аутологичных мезенхимальных стволовых клеток и стерильного биопластического коллагенового материала «Коллост». Комплексная оценка состояния тканей периодонта трех групп показала, что среди получивших стандартный лечебный комплекс хорошее состояние тканей периодонта через 1–2 года после лечения отмечалось лишь у 16,7 % пациентов 1-й группы. Включение ортодонтического лечения позволило получить хорошие результаты у 25 % пациентов 2-й группы, что на 8 % больше, чем в 1-й группе. В то же время хорошие результаты лечения выявлены у 94 % пациентов 3-й группы, которым в комплекс лечебно-профилактических мероприятий включали периодонтологическое и ортодонтическое лечение с использованием аутологичных мезенхимальных стволовых клеток, что подтверждает необходимость применения мероприятий, направленных на нормализацию положения зубов, зубных рядов и прикуса с использованием малых ортодонтических сил длительного воздействия, улучшение микроциркуляции тканей периодонта и восстановление контура маргинальной десны. Включение в комплексное лечение пациентов с рецессией десны аутологичных мезенхимальных стволовых клеток сопровождается уменьшением распространенности (1,6 раза) и интенсивности рецессии десны (1,15 мм), увеличением объема тканей в 2,6 раза, стимуляцией процессов микроциркуляции периодонта (по показателям капиллярного давления периодонта в 1,1 раза и интенсивности микроциркуляции периодонта в 3,1 раза), а также нормализацией положения зубов, зубных рядов и прикуса, что позволило получить хорошие отдаленные результаты у 94 % пациентов

ПРИМЕНЕНИЕ КЛЕТОЧНЫХ ТЕХНОЛОГИЙ ДЛЯ РЕГЕНЕРАЦИИ ТКАНЕЙ ПЕРИОДОНТА В ЭКСПЕРИМЕНТЕ

A promising scope of modern scientific research is the use of autologous and allogeneic mesenchymal stem cells for regeneration of periodontal tissues. The aim of the study was to evaluate the nature of morphological changes in the pathologically altered periodontal tissues after injection of a biotransplant containing mesenchymal stem cells of the adipose tissue immobilized on a collagen carrier in an animal experiment. In the experiment, 60 randobbred females of white rats were used as a model, whose adipose tissue was taken to obtain allogenic mesenchymal stem cells. All animals were divided into 5 groups, depending on the planned method of treatment – 10 rats each. The control group consisted of 10 laboratory animals with healthy gingiva. The experimental gingival recession model was created by the V-shaped excision of periodontal tissues. The bioplastic collagen material “Collost” gel 7 % in isolated form determines the fibrosis intensification and serves as a “matrix” for the formation of a fibrous tissue, ensures the adhesion of stem cells and their transformation into pro- and fibroblasts. Injection of a cell transplant suspension into physiological saline activates the processes of cell proliferation and transformation of fibroblast differentiating cells. Suspension of the cell transplant on a sterile bioplastic collagen material “Collost” gel 7 % enhances the effects of gel and stem cells, promotes the leveling of atrophic and dystrophic changes in the gum, strengthening a mechanical component, reducing the recession of the gum and the depth of the gingival pocket.Перспективным направлением современных научных исследований является применение аутологичных и аллогенных мезенхимальных стволовых клеток для регенерации тканей периодонта. Целью исследования являлось изучение характера морфологических изменений в тканях патологически измененного периодонта при использовании биотрансплантата на основе мезенхимальных стволовых клеток жировой ткани, иммобилизированных на коллагеновом носителе в эксперименте на животных. Для эксперимента в качестве модели использовали рандомбредных самок белых крыс в количестве 60 особей, у которых производили забор жировой ткани для получения аллогенных мезенхимальных стволовых клеток. Все животные были разделены на 5 групп в зависимости от планируемого метода лечения – по 10 крыс в каждой. Контрольную группу составили 10 лабораторных животных со здоровой десной. Создание модели экспериментальной рецессии десны осуществляли путем механического иссечения тканей периодонта V-образной формы. Биопластический коллагеновый материал «Коллост» гель 7 % в изолированном виде обусловливает интенсификацию фиброза и служит «матриксом» для формирования фиброзной ткани, обеспечивает адгезию стволовых клеток и их трансформацию в про- и фибробласты. Инъекция суспензии клеточного трансплантата в физиологическом растворе активирует процессы клеточной пролиферации и трансформации клеток фибробластного дифферона. Суспензия клеточного трансплантата на стерильном биопластическом коллагеновом материале «Коллост» гель 7 % усиливает эффекты геля и стволовых клеток, способствует нивелированию атрофических и дистрофических изменений десны, усилению механической компоненты, уменьшению рецессии десны и глубины десневого кармана

A Comparative Cyberconflict Analysis of Digital Activism Across Post-Soviet Countries

This article analyses digital activism comparatively in relation to three Post-Soviet regions: Russian/anti-Russian in Crimea and online political deliberation in Belarus, in juxtaposition to Estonia’s digital governance approach. The authors show that in civil societies in Russia, Ukraine and Belarus, cultural forms of digital activism, such as internet memes, thrive and produce and reproduce effective forms of political deliberation. In contrast to Estonia, in authoritarian regimes actual massive mobilization and protest is forbidden, or is severely punished with activists imprisoned, persecuted or murdered by the state. This is consistent with use of cultural forms of digital activism in countries where protest is illegal and political deliberation is restricted in government-controlled or oligarchic media. Humorous political commentary might be tolerated online to avoid mobilization and decompress dissent and resistance, yet remaining strictly within censorship and surveillance apparatuses. The authors’ research affirms the potential of internet memes in addressing apolitical crowds, infiltrating casual conversations and providing symbolic manifestation to resistant debates. Yet, the virtuality of the protest undermines its consistency and impact on offline political deliberation. Without knowing each other beyond social media, the participants are unlikely to form robust organisational structures and mobilise for activism offline

Origin and Post-Glacial Dispersal of Mitochondrial DNA Haplogroups C and D in Northern Asia

More than a half of the northern Asian pool of human mitochondrial DNA (mtDNA) is fragmented into a number of subclades of haplogroups C and D, two of the most frequent haplogroups throughout northern, eastern, central Asia and America. While there has been considerable recent progress in studying mitochondrial variation in eastern Asia and America at the complete genome resolution, little comparable data is available for regions such as southern Siberia – the area where most of northern Asian haplogroups, including C and D, likely diversified. This gap in our knowledge causes a serious barrier for progress in understanding the demographic pre-history of northern Eurasia in general. Here we describe the phylogeography of haplogroups C and D in the populations of northern and eastern Asia. We have analyzed 770 samples from haplogroups C and D (174 and 596, respectively) at high resolution, including 182 novel complete mtDNA sequences representing haplogroups C and D (83 and 99, respectively). The present-day variation of haplogroups C and D suggests that these mtDNA clades expanded before the Last Glacial Maximum (LGM), with their oldest lineages being present in the eastern Asia. Unlike in eastern Asia, most of the northern Asian variants of haplogroups C and D began the expansion after the LGM, thus pointing to post-glacial re-colonization of northern Asia. Our results show that both haplogroups were involved in migrations, from eastern Asia and southern Siberia to eastern and northeastern Europe, likely during the middle Holocene

Text categories of messages in the form of a political cartoon

The article deals with the political cartoon as a creolized text consisting of two parts (verbal and visual) and identifies the potential of verbal and visual means to express text categories in messages under study. The author comes to a conclusion that political cartoons are characterized with the same text categories as a homogeneous verbal text. The text categories of a political cartoon are expressed with verbal and visual means organized in personal, local, temporal and modal structures of the message. Analysis of Walter Hanel's cartoons proves the following: (1) the cartoonist expresses his own opinion using constituents of the personal structure; (2) narration perspective of the message causes its emotional tinge and subjective evaluation (the artist uses verbal means, which have certain connotations or develop ones in connection with the picture, and advantages of visual means, constituents of the modal structure); (3) constituents of the local structure function as direct and indirect local references, indicate place of action and create space of a cartoon; (4) using advantages of both codes and appealing to addressee's background knowledge, the cartoonist can specify time actual for the message, introduce traces of the past into the present and look into the future. The author of the article inclines to the opinion that verbal and visual means are equal in their contribution to the message in the form of a political cartoo

Sociological Evaluation of the Influence of International Migration on the Socio-Economic Development of the Rostov Region

Introduction. In Russia, migration is currently considered to be an important resource for replenishing the population, although the population growth resulting from migration is quite slow. Russia’s Concept of the State Migration Policy until 2025 has been revised in order to improve the situation and ensure the inflow of foreign labor migrants. The goal of this article, based on the results of the conducted study, is to reveal the attitude of the population of the host community (Rostov Region) towards an increase in the flow of foreign labor migrants in the current socio-economic circumstances, as well as the expert evaluation of the effectiveness of handling the migration situation at the regional level. Materials and Methods. The object of study conducted was the migration situation in the Rostov Region, which is one of the leaders in the socio-economic development of the macroregion and the border area of ​​the South of Russia. A survey was conducted among the general public (n = 300) using the method of standardized interviews, among university students (n = 200), using the method of questionnaire, and among experts (n = 30) using the method of semi-structured interviews. The constructivist approach was adopted as the conceptual foundation of the analysis performed. This enabled the author to use various methods of surveying the population, including university students and the expert community. Results. The performed analysis of the collected empirical material has revealed that most people in the region use the results of migrant labour in various sectors of the economy without treating migrants as competitors in the regional labor market and do not feel any noticeable influence of migrants on their lives. Experts are more critical of the prospects of integrating migrants, perceiving the growth of their number as a threat to the cultural identity of the host community. Discussion and Conclusion. Dynamic development of a region requires proactive migration policies, largely based on the loyalty of the population, including young people, to foreign migrants and their positive attitude towards integration. The analysis of the collected material has been targeted at the regional authorities implementing migration policies. The research results may prove useful to civil society institutions promoting interaction between migrants and the host community