PLASMA Th1/Th2/Th17 CYTOKINE PROFILE AND CYTOKINE GENE POLYMORPHISMS (IL12B, IL13, IL31, IL33) IN ASTHMATIC CHILDREN: A MAGNETIC MULTIPLEX ASSAY

The study of the bronchial asthma pathogenesis is an urgent problem due to its high prevalence and often developing uncontrolled severe ashma, including in childhood. The first signs of asthma development tend to occur in childhood, which causes deterioration in the patient’s quality of life and early disability. Since BA is a genetically mediated process, the severity of the disease is assumed to depend on the presence of a specific allelic variant in the mediator (e.g. cytokines) genes involved in the BA pathogenesis. The aim of this study was to search for immunogenetic markers of severe asthma in Slavs children living in Krasnoyarsk city. The quantitative indicators of the Th1/Th2/Th17-cytokine profile in children with bronchial asthma (BA) with varying disease severity, depending on the polymorphism of cytokine genes, using the method of multiplex analysis (xMAP), were first determined. Changes in the cytokine background in BA patients fit into the concept that a percentage of neutrophilic endotype, which performs its functions through Th1 and Th17-lymphocytes in severe asthma, increases. In addition, the cytokine profile data depending on concomitant acute respiratory infections were obtained. There was an imbalance when analyzing the cytokine plasma level, with a tendency to maintain the protective functions of the immune system among patients in remission. Distribution of cytokine genes was obtained: allelic variants of IL12B rs321220*G, IL13 rs1800925*C, IL31 rs7977932*C and IL33 rs7044343*T are the most common in the population sampling from Krasnoyarsk. The probability of the genotype association of cytokine genes (IL12B, IL13, IL31, IL33) with the state of the immune system in bronchial asthma with varying disease severity in children was studied: a significant association of the TT genotype IL12B rs3212220 with a low concentration of IL-12B was presented. Our data obtained can be used along with the previously obtained immunogenetic markers of severe and uncontrolled asthma in children for patient-specific prognosis of the disease nature

Delay and distortion of slow light pulses by excitons in ZnO

Light pulses propagating through ZnO undergo distortions caused by both bound and free excitons. Numerous lines of bound excitons dissect the pulse and induce slowing of light around them, to the extend dependent on their nature. Exciton-polariton resonances determine the overall pulse delay and attenuation. The delay time of the higher-energy edge of a strongly curved light stripe approaches 1.6 ns at 3.374 eV with a 0.3 mm propagation length. Modelling the data of cw and time-of-flight spectroscopies has enabled us to determine the excitonic parameters, inherent for bulk ZnO. We reveal the restrictions on these parameters induced by the light attenuation, as well as a discrepancy between the parameters characterizing the surface and internal regions of the crystal.Comment: 4 pages, 4 figure

Explication of the Methodological Difficulties of Modern Axiology

The authors focus on the group of methodological difficulties of axiology, due to its specific multifaceted subject. One of the major difficulties in the study of values is that there is no unity in the understanding of the essence of value in science. Axiological theories that exist within different philosophical and cultural philosophy of teachings represent a diversity of opinions, conclusions, decisions and methodological approaches. There are several different approaches of consideration of the category of "value", covering different spheres of social life in axiology, in values the elements of the sub-categories and subcategories are distinguished. Methodological pluralism in interpretation and typology of values are analyzing. Theoretical foundations of axiology are formed as a response to two major challenges: existential status of values and their relationship to the facts of reality. The response to these challenges in axiology was pluralization of ways of philosophizing, which is expressed in the generation of a variety of axiologically oriented traditions, based on its own research methodology and leading to the existence of a number of methodological inconsistencies. According to the results of the analysis, the authors concluded that the difficulties of methodological nature, reflecting the diversity of its subject matter, are manifested in the increasing expansion of the research field of axiology, in the unresolved range of the fundamental problems in the axiology in the existing diversity of theories, values and definitions of the concept of "value" itself and etc., this methodological situation requires a rethinking of the methodology and axiology. DOI: 10.5901/mjss.2015.v6n3s1p47

Two pathways of proton transfer reaction to (triphos)Cu(η1-BH4) via a dihydrogen bond [triphos = 1,1,1-tris(diphenylphosphinomethyl)ethane]

The interaction of alcohols of variable strength with the copper(i) borohydride complex (triphos)Cu(η1-BH4) results in a great variety of DHB complexes which encompass different mechanisms involving M–H and E–H bond (E = B, O) activation steps

INFLUENCE OF ANTIBODIES AGAINST CTLA-4 AND PD-1 UPON QUANTITIES OF THEIR TARGET RECEPTORS

Inhibitory receptors CTLA-4 and PD-1 (immune checkpoints) play a key role in regulation of immune reactions. They suppress excessive immune response against pathogenic microbes and prevent autoimmune reactions. The immune checkpoints are targets of the modern effective therapy based on human and humanized monoclonal antibodies (ipilimumab and nivolumab, tremelimumab, pembrolizumab, etc). However, despite its high efficiency compared to standard chemotherapy, the therapy based on blocking immune check points is facing several problems, i.e., high therapy cost and severe negative autoimmune-related side effects. Unfortunately, this therapy helps to minority of the patients. Hence, further studies are required to improve its efficiency and safety, as well as to search for selection criteria of the patients who would benefit from the therapy. An appealing approach to reduce negative side effects from immune checkpoint inhibition is application of the blocking antibodies, aiming for ex vivo generation of patients’ activated immune cells for cancer therapy, thus avoiding systemic drug administration. Our aim was to elucidate influence of immune checkpoint blocking antibodies on the expression of CTLA-4 and PD-1 in such an in vitro model. First of all, we have determined quantities of lymphocyte receptors in peripheral blood of healthy volunteers, or cancer patients with disseminated melanoma. Moreover, we defined effect from the addition of antibodies against immune checkpoints on proportions of cells expressing CTLA-4 and PD-1 in the population of phytohemagglutininactivated lymphocytes. Our study demonstrated that, in presence of antibodies to either of the two checkpoints during in vitro cell activation, the blockade of specific target receptor is accompanied by reduced number of cells positive for another checkpoint. Hence, the antibodies directed against PD-1 or CTLA-4 seem to suppress both negative signal cascades at once, if tested under such experimental conditions. Noteworthy, the response to blocking antibodies for different immune checkpoints varied for different donors. Our data may be used for development of effective combinations of lymphocyte activators and immune check-point inhibitors, for in vitro generation of activated lymphocytes applied for adoptive cancer therapy, as well as for prediction of possible responses to antibodies against CTLA-4 or PD-1, aiming to select the best personalized cancer immunotherapy