Phenomenon Of Tolerance Research Articles

Engineering tolerance to CLCuD in transgenic Gossypium hirsutum cv. HS6 expressing Cotton leaf curl Multan virus-C4 intron hairpin

Cotton leaf curl disease (CLCuD), caused by begomoviruses in combination with betasatellite molecule, has adversely affected cotton industry of Indian subcontinent. To devise a CLCuD-control strategy, RNAi-mediated approach was followed in this study. Gossypium hirsutum cv. HS6 plants were transformed with intron-hairpin RNAi (ihpRNAi-C4) construct carrying silencing suppressor C4 gene of Cotton leaf curl Multan virus (CLCuMuV). Efficacy of the construct in imparting CLCuD resistance was evaluated in transgenic (T0, T1) cotton lines. Accumulation of CLCuMuV/betasatellite and attenuation of CLCuD symptoms in the transgenic lines were monitored at different times interval after virus inoculation. Northern hybridization revealed the expression of C4-gene derived siRNA. Expression of the ihpRNAi transcript was recorded higher in transgenic lines expressing siRNA which supposedly targeted the C4 gene. A significant delay in detection of virus as well as betasatellite was observed in the transgenic lines. At 30 days post inoculation (dpi), none of the lines tested positive. At 45 dpi, however, it could be detected in few lines having much lower titre as compared to non-transformed control plants. Notably, till 60 dpi, no significant progression of the virus/betasatellite DNA was observed and the plants did not exhibit any characteristic CLCuD symptoms. A tolerance phenomenon leading to escape of CLCuD symptoms in the transformed cotton was described.

TOLERANCE AS A MANIFESTATION OF INDIFFERENCE

The article is devoted to the theoretical analysis of the understanding of the phenomenon of tolerance in psychology and the determination of the characteristics and probable reasons for the manifestation of such a form as tolerance of indifference, which is currently the most widespread in the world, according to the authors of this article. It is stated that there are a lot of different interpretations of the concept of tolerance in the scientific literature and they continue with an awareness of the complexity, multidimensionality and dynamic nature of this phenomenon, however, instead of identifying what unites them, which is common for the definition of tolerance, scientists are focused on attempts to offer their own, more a good understanding of it, different from the existing ones. And this actually means the absence in science of the exact meaning of this word, as well as an understanding of what exactly, what psychological phenomenon it means. And the attempts of scientists to distinguish this concept from the concept of tolerance in no way facilitate the solution of the situation. It is suggested that tolerance and intolerance should not be opposed in the context of a "positive-negative" attitude, since these concepts are not mutually exclusive, and the manifestation of intolerance under certain circumstances can be a moral phenomenon, in contrast to tolerance. It is noted that the biggest problem and still unresolved issue of the psychology of tolerance is the definition of the boundaries of manifestation of tolerance, tolerant attitude towards another person and his actions. It is concluded that the limit of the manifestation of a tolerant attitude is violation / neglect of other norms of universal human morality; that in the modern world, tolerance is not always actively manifested, more often the tolerance of indifference dominates. And it is precisely this manifestation of tolerance that has a long history (philosophical and religious), which serves as a serious basis for modern manifestations of tolerance as indifference. Tolerance of indifference is a manifestation of a stable, not always conscious, indifferent attitude to various issues of human existence, which excludes both a person's assessment of the current situation and taking responsibility for its development. The tolerance of indifference was inherited by the post-Soviet countries from totalitarianism, but the modern information society, in part, involuntarily cultivates just this kind of tolerance, gradually leveling the axiological significance of a person's moral and existential values.

CD22/Lyn-mediated suppression of trophoblast antigen-specific B cells underlies fetomaternal tolerance

Abstract The placenta releases allogeneic trophoblast antigens into maternal circulation during pregnancy. Maternal antigen presenting cells present these antigens to T cells but fail to induce strong immunogenic responses, even in the presence of danger signals. While this observation illustrates the phenomenon of fetomaternal tolerance, its cellular and molecular basis remains largely unknown. By studying the pathways mediating adaptive immune responses to a surrogate trophoblast antigen in mice, we found that maternal B cells, and not regulatory T cells, directly underlie the impairments in CD4 T cell activation. Trophoblast-antigen specific B cells, rather than dendritic cells, are the main presenters of trophoblast antigen to CD4 T cells. The B cells are themselves profoundly suppressed, thus limiting their ability to activate cognate CD4 T cells. Mechanistically, B cell suppression occurs as the result of CD22/Lyn inhibitory signaling, likely induced by sialic acid residues that coat the trophoblast-derived antigen. These results not only identify maternal B cells as key players in fetomaternal tolerance but also provide a basis for further work on B cell responses during healthy and pathologic pregnancies. More broadly, these results suggest that exploiting antigen-intrinsic properties such as sialylation may provide new therapeutic ways to ignite or inhibit antigen-specific responses outside the context of pregnancy.

An Infection-Tolerant Mammalian Reservoir for Several Zoonotic Agents Broadly Counters the Inflammatory Effects of Endotoxin.

Animals that are competent reservoirs of zoonotic pathogens commonly suffer little morbidity from the infections. To investigate mechanisms of this tolerance of infection, we used single-dose lipopolysaccharide (LPS) as an experimental model of inflammation and compared the responses of two rodents: Peromyscus leucopus, the white-footed deermouse and reservoir for the agents of Lyme disease and other zoonoses, and the house mouse Mus musculus Four hours after injection with LPS or saline, blood, spleen, and liver samples were collected and subjected to transcriptome sequencing (RNA-seq), metabolomics, and specific reverse transcriptase quantitative PCR (RT-qPCR). Differential expression analysis was at the gene, pathway, and network levels. LPS-treated deermice showed signs of sickness similar to those of exposed mice and had similar increases in corticosterone levels and expression of interleukin 6 (IL-6), tumor necrosis factor, IL-1β, and C-reactive protein. By network analysis, the M. musculus response to LPS was characterized as cytokine associated, while the P. leucopus response was dominated by neutrophil activity terms. In addition, dichotomies in the expression levels of arginase 1 and nitric oxide synthase 2 and of IL-10 and IL-12 were consistent with type M1 macrophage responses in mice and type M2 responses in deermice. Analysis of metabolites in plasma and RNA in organs revealed species differences in tryptophan metabolism. Two genes in particular signified the different phenotypes of deermice and mice: the Slpi and Ibsp genes. Key RNA-seq findings for P. leucopus were replicated in older animals, in a systemic bacterial infection, and with cultivated fibroblasts. The findings indicate that P. leucopus possesses several adaptive traits to moderate inflammation in its balancing of infection resistance and tolerance.IMPORTANCE Animals that are natural carriers of pathogens that cause human diseases commonly manifest little or no sickness as a consequence of infection. Examples include the deermouse, Peromyscus leucopus, which is a reservoir for Lyme disease and several other disease agents in North America, and some types of bats, which are carriers of viruses with pathogenicity for humans. Mechanisms of this phenomenon of infection tolerance and entailed trade-off costs are poorly understood. Using a single injection of lipopolysaccharide (LPS) endotoxin as a proxy for infection, we found that deermice differed from the mouse (Mus musculus) in responses to LPS in several diverse pathways, including innate immunity, oxidative stress, and metabolism. Features distinguishing the deermice cumulatively would moderate downstream ill effects of LPS. Insights gained from the P. leucopus model in the laboratory have implications for studying infection tolerance in other important reservoir species, including bats and other types of wildlife.

ESSENTIAL AND SUBSTANTIVE CHARACTERISTICS OF THE CONCEPT OF "TOLERANCE" AS A PROFESSIONAL QUALITY OF A TEACHER OF HIGHER EDUCATIONAL INSTITUTION

The article analyzes the essence of the concept of "tolerance", analyzes tolerance as a professional quality of a teacher of higher education, identifies its structural components. The author is of the opinion that the key constructs of personality tolerance are: tolerance as the opposite of egoism and egocentrism; tolerance as tolerance to others; tolerance as a path to goodness, truth and compassion; tolerance and norm (sense of proportion) as part of traditional culture. Based on the systematization of research on the phenomenon of tolerance in philosophical, psychological and pedagogical aspects, it was found that tolerance is a complex complex phenomenon, which is considered in various aspects and understood as acceptance of another person's personality and personality, ability to understand emotional states, desire for dialogue and cooperation in interaction, rejection of domination and violence.
 The structure of this psychological construct consists of personal, cognitive, emotional and behavioral components. The specifics of personal, cognitive, emotional and behavioral components of tolerance are analyzed.
 The author considers the selected components as normatively necessary for the successful activity of the teacher in the modern conditions of higher education reform. All of them are closely interdependent, each subsequent one is productive only in the presence of the previous one, formed at a sufficient level.
 We see the prospect of further research in the further comprehensive study of ways to prepare future research and teaching staff to cultivate tolerance.

On the question of the correlation of the phenomena of political correctness and tolerance with postliberalism

On the question of the correlation of the phenomena of political correctness and tolerance with postliberalism

Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease.

During its evolution, cancer induces changes in patients’ energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of “resistance” and “tolerance” typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to eliminate the cancer, tolerance mechanisms can utilize the symptoms of cachexia (anemia, anorexia, and fatigue) to counteract unregulated cancer growth. These notions are also sustained by the evidence that cancer cachexia may be reversible if the resistance and tolerance phases are supported by appropriate antineoplastic treatments. Accordingly, there is no doubt that anticachectic therapies have an irreplaceable role in cases of reversible cancer cachexia where, if harmoniously associated with effective antineoplastic therapies, they can contribute to preserve the quality of life and improve prognosis. Such anticachectic treatments should be based on targeting the complex immunological, inflammatory, and metabolic pathways involved in the complex pathogenesis of cachexia. Meanwhile, the role of the anticachectic therapies is very different in the stage of irreversible cachexia when the available antineoplastic treatments are not able to control the disease and the resistance mechanisms fail with the prevalence of the tolerance phenomena. At this stage, they can be useful only to improve the quality of life, allowing the patient and their family to get a better awareness of the final phases of life, thereby opening to the best spiritual remodulation of the final event, death.

Professional pedagogical tolerance in the modern system educational space of the university

The purpose of the study is to analyze pedagogical tolerance as a professional quality of a higher school teacher. Scientific novelty consists in theoretical comprehension of the actual scientific concept and the phenomenon of pedagogical tolerance. It is claimed that the effectiveness of pedagogical activity largely depends on the level of the teacher's communicative and pedagogical tolerance, which is a system of theoretical knowledge about tolerance, practical skills, and personal qualities that ensure readiness for professional activity. Particular attention is paid to the importance of the teacher's tolerance for the education of tolerance among students. As a result, it is proved that the educational process with the use of interactive teaching methods is the main factor in the development of a tolerant culture of personal communication, since they are focused on broader interaction of students not only with the teacher, but also with each other and on the development of students' activity in the learning process. The data obtained can be used to introduce an innovative approach to the organization of the advanced training system at the university, which will allow mastering communicative competencies, the skills of psychological and tolerant pedagogical influence.

On the Relationship Between Uncertainty Tolerance and Hardiness in Adolescents

Objective – identify the relationship between the phenomena of uncertainty tolerance and hardiness in adolescents. Uncertainty tolerance (UT) is understood as a personality trait that manifests itself in an ability to accept uncertainty and act confidently in unstable situations. Adolescence is characterized as a period of instability. It is thus assumed that uncertainty tolerance is a significant parameter in the structure of adolescents’ hardiness. The research was designed to identify the relationship between uncertainty tolerance and hardiness in adolescents using Spearman’s rank correlation coefficient. Survey respondents: 66 schoolchildren in grades 9 and 11 (15–18 years old), of which 34 are boys and 32 are girls. For the research, a set of methods was used. Hardiness Survey (S. Maddi adapted by D. A. Leont’ev); McLane’s Multiple Stimulus Types Ambiguity Tolerance Scale-I ((MSTAT-I) adapted by E. G. Lukovitskaia); Adaptive behavioural strategies Questionnaire (adolescent form: ASP‑1) by N. N. Mel’nikova. The results of the research indicate that the relationship between uncertainty tolerance to and the scales (p ≤ 0.0001) of Risk Acceptance (r = 0.75), Control (r = 0.71), Engagement (r = 0.65), Vitality (r = 0.65) has been determined. Empirical data contribute to the understanding of uncertainty tolerance as a basic personality trait that contributes to the effective organization of life with a limited amount of information about future events. Building hardiness enables adolescents to cope with age-related challenges in a more efficient way

Комунікативна толерантність у публічному управлінні як чинник інтеграції в європейську систему гуманістичних цінностей

The article analyzes the term «communicative tolerance» through the prism of the significance of this phenomenon not only in the individual dimension as an indicator of the external culture of the individual, but also in the social – as an assessment of public managers in terms of citizens. The opinions of scholars on this issue and the positions of international law that interpret communicative tolerance as a humanistic value that characterizes European society and is needed by Ukrainians to integrate into it, which is the goal of modern Ukraine. It is emphasized that the communicative tolerance of a public servant is defined in two dimensions - as a component of his professional competence and as an indicator of citizens' trust in general in public authorities and local self-government. This corresponds to the binary specifics of considering the phenomenon of general tolerance – at the individual and international levels, where the first implies a more humanistic orientation, and the second – the current desire for peaceful development of relations in the world. Dichotomous pairs are defined as conclusions: tolerance as social indifference, uncertainty - tolerance as a sign of worldview activity; tolerance as patience or indulgence – tolerance as an active affirmation of human rights, democracy; tolerance as a tolerance of social injustice, humble acceptance of other people's beliefs - tolerance as the preservation of one's own individuality and recognition of other people's beliefs. In defining the features of a public manager, elements of communicative tolerance are noted: professional (communication with citizens); moral and ethical (evaluated by citizens); actually communicative (creating a trusting atmosphere of communication); administrative (form the assessment of citizens of public service in general and public authorities in particular). Among such features, the leading ones are coordination and constructive ones, which consist in anticipating and leveling potential conflicts that may occur in society and the community.

ПСИХОЛОГІЧНІ ОСОБЛИВОСТІ ПРОЯВУ ГЕНДЕРНОЇ ТОЛЕРАНТНОСТІ В ЮНАЦЬКОМУ ВІЦІ

Статтю присвячено визначенню психологічних особливостей прояву гендерної толерантності та її структурних компонентів в юнацькому віці. Зазначений віковий період знаменується виникненням нової соціальної ситуації розвитку, центром якої є перехід до самостійного життя. Продовжується інтенсивний розвиток самосвідомості, молоді люди самовизначаються в системі моральних цінностей, принципів, норм і правил поведінки, усвідомлюють особисту соціальну відповідальність. Відповідно до такої ситуації розвитку молодого покоління в умовах трансформаційних процесів в економічній, політичній і соціальній сферах, важливим є питання гармонізації міжстатевих стосунків молоді завдяки вихованню толерантного ставлення до представників своєї та протилежної статі. Прояв гендерної толерантності в юнацькому віці сприяє: створенню психологічно комфортних умов для спільної діяльності представників обох статей; досягненню міжособистісного й міжгрупового взаємопорозуміння і поваги в різних сферах життєвої взаємодії; забезпеченню ефективних психолого-педагогічних умов для вироблення у юнаків і юнок необхідних індивідуально-особистісних якостей щодо успішного протистояння стереотипним уявленням і тиску соціуму. Мета статті полягала в дослідженні психологічних особливостей прояву гендерної толерантності та сформованості її компонентів у юнаків та юнок. У процесі емпіричного дослідження була використана: методика «ВІКТІ: види та компоненти толерантності» (авт. Г.Л. Бардієр), кількісний та якісний аналіз отриманих результатів проводився за шкалами «гендерна толерантність», «когнітивний компонент», «афективний компонент», «діяльнісно-стильовий компонент» гендерної толерантності. Констатовано, що майже в половини представників юнацького віку рівень гендерної толерантності знаходиться на середньому (наближеному до низького) рівні; майже третина юнацтва має низький рівень гендерної толерантності; й лише п’ята частина має сформовану гендерну толерантність (високий рівень). При аналізі сформованості складових гендерної толерантності (когнітивної, емоційної, поведінкової) встановлено, що знижені показники більше властиві хлопцям, що виявляється в зниженій рефлексивності, обмеженій емоційній і поведінковій саморегуляції.
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ظاهِرَةُ التَّسامُحِ فی التُّراثِ النَّحْویّ: مَعالِمُها، وَمُسَوِّغاتُها

الملخص تتناول هذه الورقة ظاهرة التسامح النحوي في العربية کما تبدو من خلال الأقوال والتطبيقات المختلفة للنحاة العرب، وهي ظاهرة تشکل جانبا من جوانب الترخص في الدرس النحوي. وتعود أهمية بحث هذه الظاهرة إلى ضرورة جمع تطبيقاتها المختلفة، والحاجة إلى تأطير نظامها کما يظهر في التراث العربي. تشتمل الدراسة على مبحثين تسبقهما مقدمة، وتمهيد، وتتلوهما خاتمة؛ وذلک لتغطية أبعاد هذه الظاهرة من حيث المفهوم، والتطبيقات، والدواعي. تعالج المقدمة التعريف بالموضوع، وأهمية دراسته، وصعوباتها. ثم يقدم التمهيد لمحة موجزة عن تأصيل مصطلحات الظاهرة لغة واصطلاحا، ثم يستعرض بإيجاز نشأتها وتطورها في الدرس النحوي. وبينما يبحث المبحث الأول ملامح الظاهرة المختلفة مقدما أمثلة لکل ملمح منها، يعالج المبحث الثاني الأسباب أو المبررات المختلفة لتطبيقات هذه الظاهرة. ثم تقدم الخاتمة نتائج الدراسة وتوصيات البحث. Abstract This paper deals with the phenomenon of tolerance in Arabic as it appears through the different sayings and pracitces of Arab grammarians. This phenomenon brings together the various reasons or justifications that clarify and explin the informal grammatical expressions the Arab gramarians have used. The importance of examining this phenomenon goes back to the necessity for collecting its different applictions and the need for framing its system in Arabic language as it is shown in the Arabic heritage. The paper includes two chapters, or parts, preceded by an introduction and a preface, and followed by a conclusion in order to cover the dimensions of this phenomenon in terms of the concept and applications, and its Justifications. While he introduction deals with the notion, the importance of studying it, and its difficulties, the preface provides a brief overview of differents terms of the phenomenon and briefly reviews the beginings of the phenomenon and its development in the grammatical study. While Chapter I investigates its different features introducing various examples for each one of them, chapter II investigates the various reasons or justifications for the different applications of this phenomenon. The conclusion provides the results of the study and recommendations of the paper.

Future perspectives from lung cancer pre-clinical models: new treatments are coming?

Lung cancer currently stands out as both the most common and the most lethal type of cancer, the latter feature being partly explained by the fact that the majority of lung cancer patients already display advanced disease at the time of diagnosis. In recent years, the development of specific tyrosine kinase inhibitors (TKI) for the therapeutic benefit of patients harboring certain molecular aberrations and the introduction of prospective molecular profiling in the clinical practice have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, the identification of the best strategies to enhance treatment effectiveness and to avoid the critical phenomenon of drug tolerance and acquired resistance in patients with lung cancer still remains an unmet medical need. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two complementary approaches to define tumor heterogeneity and clonal evolution in a non-invasive manner and to perform functional studies on metastatic cells. Finally, the recent discovery that the tumor microenvironment architecture can be faithfully recapitulated in vitro represents a novel pre-clinical frontier with the potential to optimize more effective immunology-based precision therapies that could rapidly move forward to the clinic.

Allogeneic Embryos Disregulate Leukemia Inhibitory Factor (LIF) and Its Receptor in the Porcine Endometrium During Implantation.

Despite its advantages for pig breeding, embryo transfer (ET) has a major handicap: high embryo mortality during the pre- and implantation period, probably caused by divergent phenomena of tolerance between the immunologically unrelated (i.e., allogeneic) embryos and the recipient sow. Thus, to reach a similar maternal tolerance as in conventional breeding by artificial insemination (AI) would be the key to ET-success. For this reason, we studied the expression of the leukemia inhibitory factor (LIF) cytokine and its receptor in the pig endometrium during the implantation period (days 18 and 24) in sows subjected to ET (AL group) vs. post-cervical-AI controls (Hemi-AL group). Quantification of expression was performed at both mRNA (rt-qPCR) and protein (WB) levels. The expression of endometrial LIF on day 24 was considerably lower in ET than in AI pregnancies. Correlations between endometrial mRNA levels of LIF and LIF-R showed that, contrary to early AI-pregnancies, ET-pregnancies lack an inverse relation between cytokine and receptor levels. In conclusion, ET-pregnancies lack sufficient endometrial levels of LIF to develop adequate immunotolerance mechanisms to prevent the rejection of allogeneic ET-embryos.

Tolerance development in children undergoing repeated exposure to anesthesia drugs for radiation therapy

Background & Objectives: Radiation therapy is one of the modalities used in cancer treatment to destroy rapidly growing tumor mass. The fractionated radiation session targets up to four fields of 90 sec each, over 10-15 min. Young children require deep sedation or general anesthesia to make them immobile, for the safe delivery of radiation fractions. Common drugs used for sedation are propofol, ketamine and midazolam. Repeated exposure to anesthetic drugs over a short period of time may lead to development of tolerance and increased dose requirements.
 We aimed to determine if drug tolerance phenomenon develops in children receiving frequent doses of anesthetic drugs over a short time period. 
 Methodology: This is a retrospective observational study of the pediatric population who underwent frequent radiotherapy sessions with deep sedation from January to May 2019. The data of the first and last day of drugs administered was analyzed to determine if the dose requirement for any of the three drugs increased over time.
 Results: We collected data of twenty-one patients and applied two tailed student’s t-test on the mean dose of drugs on the first day and the last day of the treatment. It remained unchanged with insignificant p value (propofol p = 0.15; midazolam p = 0.5; ketamine p = 0.32). To minimize the drug augmenting each other’s effect, multilinear regression analysis of the drugs over the time period showed that there was neither an increase nor a decrease in the doses used (αi- propofol coefficient 0.019 ± 0.053; βi- midazolam coefficient -0.002 ± 0.007; γi- ketamine coefficient 0.049 ± 0.218)). The overall duration of the recovery time was not different from the first to the last day of radiotherapy.
 Conclusion: Frequent and repeated doses of sedative drugs over a short period of time in children undergoing repeated deep sedation for radiation therapy, do not result in the development of tolerance. 
 Key words: Sedation; Tolerance; Radiotherapy
 Citation: Iqbal A, Saleem H, Durrani RS. Tolerance development in children undergoing repeated exposure to anesthesia drugs for radiation therapy. Anaesth. pain intensive care 2020;24(5):
 Received: 7 July 2020, Reviewed: 26 August 2020, Accepted: 3 September 2020

Mechanisms of Antibiotic Tolerance in Mycobacterium avium Complex: Lessons From Related Mycobacteria.

Mycobacterium avium complex (MAC) species are the most commonly isolated nontuberculous mycobacteria to cause pulmonary infections worldwide. The lengthy and complicated therapy required to cure lung disease due to MAC is at least in part due to the phenomenon of antibiotic tolerance. In this review, we will define antibiotic tolerance and contrast it with persistence and antibiotic resistance. We will discuss physiologically relevant stress conditions that induce altered metabolism and antibiotic tolerance in mycobacteria. Next, we will review general molecular mechanisms underlying bacterial antibiotic tolerance, particularly those described for MAC and related mycobacteria, including Mycobacterium tuberculosis, with a focus on genes containing significant sequence homology in MAC. An improved understanding of antibiotic tolerance mechanisms can lay the foundation for novel approaches to target antibiotic-tolerant mycobacteria, with the goal of shortening the duration of curative treatment and improving survival in patients with MAC.

Nanoparticulate Antibiotic Systems as Antibacterial Agents and Antibiotic Delivery Platforms to Fight Infections

Today’s human society, product of decades of progress in all fields of knowledge, would have been unimaginable without the discovery of antibiotics and more generally of antimicrobials. However, from the beginning, the scientific community was aware that microorganisms through various strategies were able to hinder and render vain antibiotic action. Common examples are the phenomena of persistence, tolerance, and resistance, up to the creation of the feared bacterial biofilms. Antibiotics are a precious but equally labile resource that must be preserved but at the same time reinforced to safeguard their effectiveness. Nanoparticulate systems such as nanobactericides, with their inherent antibacterial activity, and nanocarriers, which operate as drug delivery systems for conventional antibiotics, are innovative therapies made available by nanotechnology. Inorganic nanoparticles are effective both as nanobactericides (AgNPs, ZnONPs, and TiO2NPs) and as nanocarriers (AgNPs, AuNPs, ZnONPs, and TiO2NPs) against sensitive and multi-drug-resistant bacterial strains. Liposomes are among the most studied and flexible antibiotic delivery platforms: conventional liposomes allow passive targeting at the mononuclear phagocytic system (MPS); “stealth” liposomes prevent macrophage uptake so as to eradicate infections in tissues and organs outside MPS; thanks to their positive charge, cationic liposomes interact preferentially with bacterial and biofilm surfaces, acting as innate antibacterials as well as drug delivery systems (DDS); fusogenic liposomes have fluid bilayers that promote fusion with microbial membranes; and finally, ligand-targeted liposomes provide active targeting at infection sites. Dendrimers are among the most recent and attractive nanoparticulate systems, thanks to their multibranched nanoarchitecture, which equipped them with multiple active sites for loading antibiotics and also interacting with bacteria. Finally, nanoantibiotics represent a new hopeful generation of antibiotic candidates capable of increasing or even restoring the clinical efficacy of “old” antibiotics rendered useless by the resistance phenomena.

CONCEPTUAL FRAMEWORK OF THE MODEL OF FORMING INTERETHNIC TOLERANCE IN THE MULTICULTURAL ENVIRONMENT OF THE UNIVERSITY

The aim of this research is to study the state, dynamics and factors affecting the interethnic relations of young people in the field of education. This article discusses the conceptual foundations of the structural and content model of forming interethnic tolerance of young people in a multicultural environment of the university. Particular attention is paid to the study of new educational strategies and approaches that can create the desired socio-cultural and theoretical tolerance of representatives of other cultures, ethnic groups and religions. The research was a mixed method research and it made use of both quantitative and qualitative data. Secondary data for the article was derived from the scientific publications of other researchers and primary data was collected with the help of focus groups and indepth interviews.The 1000 participants of the research were carefully selected to represent nationals of other countries, culture and religion, to reduce the bias that sociological studies exhibit. The hierachy technique was used to analyze qualitative data. The authors present the results and analysis of sociological research for the analysis of interethnic tolerance of young people. It focuses on the psychological and pedagogical content of the phenomenon of interethnic tolerance, that can be taught to students in school. The authors offer evidence-based conclusions and recommendations on the organization of the process of forming interethnic tolerance of young people in a multicultural environment of the university.

Linking Brassinosteroid and ABA Signaling in the Context of Stress Acclimation.

The important regulatory role of brassinosteroids (BRs) in the mechanisms of tolerance to multiple stresses is well known. Growing data indicate that the phenomenon of BR-mediated drought stress tolerance can be explained by the generation of stress memory (the process known as ‘priming’ or ‘acclimation’). In this review, we summarize the data on BR and abscisic acid (ABA) signaling to show the interconnection between the pathways in the stress memory acquisition. Starting from brassinosteroid receptors brassinosteroid insensitive 1 (BRI1) and receptor-like protein kinase BRI1-like 3 (BRL3) and propagating through BR-signaling kinases 1 and 3 (BSK1/3) → BRI1 suppressor 1 (BSU1) ―‖ brassinosteroid insensitive 2 (BIN2) pathway, BR and ABA signaling are linked through BIN2 kinase. Bioinformatics data suggest possible modules by which BRs can affect the memory to drought or cold stresses. These are the BIN2 → SNF1-related protein kinases (SnRK2s) → abscisic acid responsive elements-binding factor 2 (ABF2) module; BRI1-EMS-supressor 1 (BES1) or brassinazole-resistant 1 protein (BZR1)–TOPLESS (TPL)–histone deacetylase 19 (HDA19) repressor complexes, and the BZR1/BES1 → flowering locus C (FLC)/flowering time control protein FCA (FCA) pathway. Acclimation processes can be also regulated by BR signaling associated with stress reactions caused by an accumulation of misfolded proteins in the endoplasmic reticulum.

Increased TLR4 pathway activation and cytokine imbalance led to lipopolysaccharide tolerance in monocytes from preeclamptic women.

Preeclampsia (PE) is a pregnancy syndrome characterized by a systemic inflammatory response, and endogenous activation of monocytes. This study aimed to determine whether the activation of monocytes from preeclamptic women might interfere with the response to lipopolysaccharide (LPS)-in vitro stimulation. Fifty-two preeclamptic women and 32 normotensive (NT) pregnant women were included. Monocytes from peripheral blood were cultured with or without LPS. TLR4 expression was analyzed by flow cytometry, NF-κB activity was determined in nuclear extracts and cytokines production was evaluated by ELISA. Endogenous TLR4 ligands such as Hyaluronan, HMGB1 and Hsp70 were determined in plasma. The endogenous TLR4 expression and activation of NF-κB were statistically higher in monocytes from women with PE compared to NT group. Early-onset PE showed higher TLR4 expression compared to late-onset PE. Plasma levels of Hyaluronan, HMGB1, and Hsp70, as well as endogenous production of inflammatory cytokines, were elevated whilst lower production of IL-10 was observed in the PE group. After culture with LPS, monocytes presented lower NF-κB activation, TNF-α and IL-12 production in PE groups than in the NT group. The study demonstrates endogenous activation of monocytes from preeclamptic women, accompanied by higher expression of TLR4, NF-κB activation and elevated production of pro-inflammatory cytokines. The higher plasma levels of the TLR4 ligands hyaluronan, HMGB1 and hsp70, as well as the high concentration of TNF-α endogenously produced by monocytes, could induce the LPS tolerance phenomenon in these cells. These results suggest that monocytes play an important role in the maternal excessive systemic inflammatory response in PE.