E 27 Effect of "Profetal" on differentiation and functional activity of human mononuclear leukocytes [Text] / O. V. Lebedinskaya, N. P. Velizheva, F. V. Donenko, V. A. Chereshnev // Bulletin of experimental biology and medicine. - 2006. - Vol. 141, № 4. - P536-543 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): ALPHA-FETOPROTEIN -- "PROFETAl" -- MONONUCLEAR LEUKOCYTES \\\\expert2\\nbo\\Bulletin of Experimental Biology and Medicine\\2006, v.141, N 4, p. 536.pdf |
H 91 Human immunodeficiency virus infection: From biological observations to mechanistic mathematical modelling / G. Bocharov, V. A. Chereshnev, I. C. Gainova [et al.] // Mathematical modelling of natural phenomena. - 2012. - Vol. 7, № 5. - P78-104. - Bibliogr. : p. 93-104 (275 ref.) Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): HOST-PATHOGEN INTERACTION -- IMMUNE SYSTEM -- HUMAN IMMUNODEFICIENCY Аннотация: HIV infection is multi-faceted and a multi-step process. The virus-induced pathogenic mechanisms are manifold and mediated through a range of positive and negative feedback regulations of immune and physiological processes engaged in virus-host interactions. The fundamental questions towards understanding the pathogenesis of HIV infection are now shifting to 'dynamic' categories: (i) why is the HIV-immune response equilibrium finally disrupted? (ii) can one modify the dynamic equilibrium for host benefit? (iii) can one predict the outcome of a system perturbation via antiviral drugs or drugs modulating the host immune response dynamics? Answering these questions requires a major interdisciplinary effort, and in particular, the development of novel mathematical approaches for a coherent quantitative description and prediction of intra-patient HIV evolution, the immunological responses to HIV infection, and the systems level homeostatic regulation of specific effector and regulatory lymphocyte populations in correlation with disease status. Here we summarized fundamental biological features of HIV infection and current mathematical modelling attempts to understand HIV pathogenesis \\\\expert2\\NBO\\Mathematical Modelling and Natural Phenomena\\2012. V. 7, N 5. P. 78-104.pdf |
E 27 Effect of myelopeptides on reactive oxygen species generation and IL-1beta and TNF-alpha production by peripheral blood cells / // Patologicheskaia fiziologiia i èksperimental'naia terapiia. - 2012. - № 1. - P19-22 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): IL1B PROTEIN -- HUMAN -- IMMUNOLOGICAL ADJUVANT Аннотация: Myelopeptides MP-3, MP-5, and MP-6 were found to suppress zymosan-induced production of reactive oxygen species by leukocytes both under one-way introduction and under pretreatment. All of myelopeptides under examination in case of one-way introduction in cultures with zymosan demonstrated a decrease in zymosan-stimulated (1500 mkg/ml) production of IL-1beta, and activation of spontaneous production of this cytokine by whole blood cells. TNF-alpha production under myelopeptide effect was lowered in cultures with 150 mkg/ml zymosan. Under pretreatment myelopeptides did not render effect on IL-1beta and TNF-alpha production, with the exception of single stimulating effect of MP-5 on IL-1beta level in spontaneous cultures. Using comparative analysis the difference in direction and expressivity of effects of various myelopeptides was not revealed that suggests the existence of common mechanism of action in this group of peptide bioregulators. |
I-57 In vitro cytokine stimulation assay for glycolipid biosurfactant from Rhodococcus ruber: Role of monocyte adhesion / S. V. Gein, M. S. Kuyukina, I. B. Ivshina, V. A. Chereshnev // Cytotechnology. - 2011. - Vol. 63, № 6. - P559-566. - Bibliogr. : p. 565-566 (23 ref.) Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): CYTOKINE-STIMULATING ACTIVITY -- GLYCOLIPID BIOSURFACTANT -- MONOCYTE ADHESION Аннотация: Glycolipid biosurfactant (GLB) from Rhodococcus ruber IEGM 231 was found to stimulate tumor necrosis factor-α (TNF-α), interleukin (IL) -1β and IL-6 production when applied as an ultrasonic emulsion to the adherent human peripheral blood monocyte culture. However, a lack of cytokine-stimulating activity was registered with the GLB applied as a hydrophobic film coating in 24-well culture plates, indicating that it may have been due to its inhibitory effect on monocyte adhesion. The mode of GLB application may therefore play an important role in in vitro assay of immunostimulatory activity of this compound as well as other bacterial glycolipids. Additionally, GLB from R. ruber displayed no cytotoxicity against human lymphocytes and therefore could be proposed as a potential immunomodulating and antitumor ag \\\\expert2\\NBO\\Cytotechnology\\2011. V. 63, N 6. P. 559-566.pdf |
I-56 Impact of bacterial autoregulatory molecules (homoserine lactones and alkylhydroxybenzenes) on the oxidative metabolism of the cell effectors of natural immunity / D. G. Deryabin, T. G. Sviridova, G. I. El'-Registan, V. A. Chereshnev // Microbiology. - 2013. - Vol. 82, № 2. - P133-141 Рубрики: БИОЛОГИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): ALKYLHYDROXYBENZENES -- CHEMOLUMINESCENCE -- HOMOSERINE LACTONES Аннотация: We investigated the impact of bacterial regulators homoserine lactones (HSLs) and alkylhydroxybenzenes (AHBs) (which are present in human fluids at pico- and nanomolar concentrations) on neutrophile oxidative metabolism. The HSL and AHB effects were determined using a test based on induced luminol-dependent chemoluminescence of neutrophiles in human peripheral blood. In this test, neutrophiles were preincubated with chemical analogs of bacterial autoregulators with different lengths of the hydrocarbon radical, such as HSL · HCl, C6- and C12-HSL, and C1-, C6-, and C12-AHB. We revealed that they suppressed the chemoluminescence and, accordingly, the oxidative metabolism of neutrophiles. This effect was more significant with HSLs than with AHBs. Within each of the two groups, the effect increased with an increase in the length of the hydrocarbon chain of the homologues. High concentrations of long-chain autoregulators of both types produce a cytotoxic effect that is associated with apoptosis in the case of C12-HSL and with cell membrane damage in the case of C12-AHB. The effects of low HSL and AHB concentrations involve their protein-modifying properties and result in changes in the activities of neutrophile oxidative enzymes. To a lesser extent, these effects are due to the pro- and antioxidant activities of HSLs and AHBs, respectively. In light of the results obtained, the HSL and AHB effects are to be considered as a novel mechanism of regulating the activities of cell effectors of natural innate immunity. In symbiotic and parasitic systems, the mechanism involves the bimodal pattern of the effects of HSLs and AHBs that vary depending on their structure and concentrations |
T 44 The role of monocytes in the effects of β-endorphin and selective agonists of μ-and δ-opiate receptors on the proliferative activity of peripheral blood lymphocytes / S. V. Gein, T. A. Baeva, O. N. Gein, V. A. Chereshnev // Human Physiology. - 2006. - Vol. 32, № 3. - P346-350 Рубрики: БИОЛОГИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): MONOCYTES -- BETA ENDORPHIN -- BLOOD LYMPHOCYTES Аннотация: The effects of β-endorphin under the conditions of naloxone hydrochloride blockade of opiate receptors, as well as the effects of the selective agonists of μ-and δ-receptors DAGO and DADLE and the effects of melanocyte-potentiating factor (MPF), on the in vitro proliferative response of lymphocytes were studied. The dose-effect dependence indicated stimulating effects of β-endorphin, DAGO, and DADLE on the proliferative response in the presence of phytohemagglutinin (PHA). The tetrapeptide MPF, which is the C-terminal sequence of β-endorphin, had almost no effect on the proliferative activity of lymphocytes. β-Endorphin, naloxone, and the μ-and δ-receptor selective agonists enhanced the proliferative response of lymphocytes in an unfractionated cell culture, whereas β-endorphin, naloxone, and DAGO suppressed the proliferative activity of lymphocytes in the mononuclear fraction purified of monocytes. In both cases, the naloxone blockade of opiate receptors enhanced rather than eliminated the β-endorphin e \\\\expert2\\nbo\\Human Physiology\\2006. V. 32, N 3. P. 346-350.pdf |
C 98 Cytotoxicity of N-dodecanoyl-L-homoserine lactone and 5-N-dodecyl resorcinol to human granulocytes and monocytes: A comparative study [Electronic resource] / T. G. Sviridova, D. G. Deryabin, O. Cyganok, V. A. Chereshnev // Central European Journal of Immunology. - 2013. - Vol. 38, № 3. - P310-316. - Bibliogr. : p. 316 (21 ref.) Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): 5-N-DODECYL RESORCINOL -- CYTOTOXICITY -- APOPTOSIS Аннотация: Small molecules originating from microbes (SMOMs) play a significant role in bacterial-bacterial communication and in interactions between bacteria and their hosts. The aim of this study is a comparative analysis of the cytotoxic activity to human granulocytes and monocytes of two structurally close SMOMs: N-dodecanoyl-L-homoserine lactone (C12-HSL) and 5-N-dodecyl resorcinol (C12-AR). Cell viability was determined by Trypan blue dye exclusion. To distinguish cell death mechanisms, both necrosis and apoptosis tests were carried out. Cells undergoing apoptosis were identified by caspase-3 activity and the level of histone-associated DNA fragments. To evaluate cell lysis, the lactate dehydrogenase release test was used. In addition, the SMOM's action on erythrocyte membrane stability was investigated. The investigated SMOMs in micromolar concentrations showed more dose-dependent cytotoxicity against granulocytes than monocytes, but they used different mechanisms to impinge on the cell death pathway. C12-HSL specifically induced apoptosis similar to the activity previously reported for 3-oxo-N-dodecanoyl-L- homoserine lactone that originated from Pseudomonas aeruginosa. In contrast, C12-AR induced fast cytolytic effects (necrosis) as shown by the release of cytoplasmic lactate dehydrogenase, and presumably were defined by cellular membrane destabilisation. Our data demonstrate that both C 12-HSL and C12-AR can eliminate key defence cells, which would otherwise participate in the destruction of pathogenic bacteria. These results reinforce the SMOMs bifunctionality concept that such bacterial molecules not only regulate bacterial-bacterial interactions but also break immune defences as a new and important mechanism of host evasion \\\\expert2\\nbo\\Central European Journal of Immunology\\2013. Vol.38, №3. С. 310-316.pdf |
S 96 Sviridova, T. G. Homoserine lactones and resorcinolic lipids inhibit In vitro pro-and anti-inflammatory cytokine production / T. G. Sviridova, D. G. Deryabin, V. A. Chereshnev // Research Journal of Immunology. - 2013. - Vol. 6, № 1. - P7-16. - Библиогр.: с. 14-16 (27 ref.) Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): HOMOSERINE LACTONES -- RESORCINOLIC LIPIDS -- IMMUNE SYSTEM Аннотация: Homoserine Lactones (HSLs) and Resorcinolic Lipids (RLs) originating from microbes and plants influence immune system, however, it is currently unclear whether HSLs and RLs are activators or suppressors of the cytokine network, especially in humans. A study has been carried out to investigate the effects of pure, synthetic HSLs and RLs with different chain lengths on pro-and anti-inflammatory cytokines produced by human blood monocyte cultures. Human monocytes (macrophages and lymphocytes) were collected from leukocyte-rich plasma, separated on a double density gradient, pre-treated with HSLs or Rls and then were inducted with standard either lipopolysaccharide or phytohemagglutinin stimulus. Quantitative assays for pro-and anti-inflammatory cytokines in the monocyte culture supernatants were performed using enzyme immunoassay kits for the quantitative determination of IL-1β, IL-2, IL-4, IL-10, TNF-α and IF-γ. We observed differences in cytokine production according to HSL and RL pre-treatment, increasing in the following order: IL-1β→IL-2≈IL-10≈TNF-α→IL-4→IF-γ. HSLs have been shown more pronounced inhibitory effects than Rls and long-chained homologs were more active than short-chained ones. Our study suggests that some small molecules originating from microbes and plants play an important role in cytokine network regulation and the immunomodulatory effect of HSLs and RLs may obstruct host defenses and affect inflammatory processes \\\\expert2\\NBO\\Research Journal of Immunology\\2013. V. 6, N 1. P. 7-16.pdf |
Применение защитных белков теплового шока-70 для борьбы с COVID-19 / В. А. Черешнев, С. Б. Оникиенко, А. В. Земляной, С. В. Абкин // Журнал инфектологии. - 2022. - Т. 14, № 2, Приложение 1 : Материалы VIII Конгресса Евро-Азиатского общества по инфекционным болезням, Санкт-Петербург, 17-19 мая 2022. - С. 134-135 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): COVID 19 -- КОРОНАВИРУС -- ШОК ТЕПЛОВОЙ -- БЕЛКИ ЗАЩИТНЫЕ Аннотация: We investigated the impact of bacterial regulators homoserine lactones (HSLs) and alkylhydroxybenzenes (AHBs) (which are present in human fluids at pico- and nanomolar concentrations) on neutrophile oxidative metabolism. The HSL and AHB effects were determined using a test based on induced luminol-dependent chemoluminescence of neutrophiles in human peripheral blood. In this test, neutrophiles were preincubated with chemical analogs of bacterial autoregulators with different lengths of the hydrocarbon radical, such as HSL · HCl, C6- and C12-HSL, and C1-, C6-, and C12-AHB. We revealed that they suppressed the chemoluminescence and, accordingly, the oxidative metabolism of neutrophiles. This effect was more significant with HSLs than with AHBs. Within each of the two groups, the effect increased with an increase in the length of the hydrocarbon chain of the homologues. High concentrations of long-chain autoregulators of both types produce a cytotoxic effect that is associated with apoptosis in the case of C12-HSL and with cell membrane damage in the case of C12-AHB. The effects of low HSL and AHB concentrations involve their protein-modifying properties and result in changes in the activities of neutrophile oxidative enzymes. To a lesser extent, these effects are due to the pro- and antioxidant activities of HSLs and AHBs, respectively. In light of the results obtained, the HSL and AHB effects are to be considered as a novel mechanism of regulating the activities of cell effectors of natural innate immunity. In symbiotic and parasitic systems, the mechanism involves the bimodal pattern of the effects of HSLs and AHBs that vary depending on their structure and concentrations |
I-70 Investigation of immune system functioning and development of methods for immune correction therapy of workers from defence industry (Leveling of unfavorable effects from ionizing radiation and toxic chemical compounds on a human body) / B. A. Bachmetyev, V. A. Chereshnev, N. N. Kevorkov, S. V. Shirshev // Scientific-technical potential of the Western Urals for conversion of military industrial complex: proceedings. - Perm, 2001. - P168-171 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): IMMUNE SYSTEM \\\\Expert2\\NBO\\Электрон. библиотека (Отеч.периодика)\\Черешнев В. А\\Scientific-technical potential, 2001 P. 168-171.pdf |
M 85 Morova, A. A. Human endoecology and diseases occurrence / A. A. Morova, V. A. Chereshnev // The 1995 International Co-Conferences on Environmental Pollution (ICEP`95) and Neuroimmuno Interactions and Environment (ICONE`95). - Saint Petersburg, 1995. - P153 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): DISEASES OCCURRENCE |
A 53 An extremal shift method for control of HIV infection dynamics / G. Bocharov, A. V. Kim, A. V. Krasovskii [et al.] // Russian Journal of Numerical Analysis and Mathematical Modelling . - 2015. - Vol. 30, № 1. - P11-25 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): HIV INFECTION -- OPTIMAL OPEN-LOOP CONTROL -- EXTREMAL SHIFT METHOD Аннотация: Optimal control problems for mathematical models describing HIV infection dynamics in a human body are considered in the paper. An overview of current approaches to solution of control problems for models of HIV dynamics is presented for techniques related to construction of optimal programme (open loop) or positional (feedback) controls for various criteria of control process quality and is based on the Pontryagin's maximum principle and the Bellman's theory of dynamic programming, respectively. In the framework of the theory of positional differential games of Krasovskii, there are constructive and efficient methods of synthesis of controls for different classes of dynamical systems. In this paper we present a formalization of a control problem for HIV infection considered as a corresponding positional differential game. The control algorithm based on the method of extremal shift is applied to the ODEs model of HIV infection. The numerical implementation of the extremal shift method is developed to construct the control taking the system to a neighbourhood of a given trajectory using the information on the dynamics of the guides or leaders. \\\\expert2\\nbo\\Russian Journal of Numerical Anal. and Math. Modelling\\2015. V.30, N. 1. P. 11-30.pdf |
M 39 Mathematical modelling of the within-host HIV quasispecies dynamics in response to antiviral treatment [Text] / G. A. Bocharov, I. S. Telatnikov, V. A. Chereshnev [et al.] // Russian Journal of Numerical Analysis and Mathematical Modelling. - 2015. - Vol. 30, № 3. - P157-170 : il. - Bibliogr. : p. 169-170 (29 ref.) Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): MATHEMATICAL MODEL -- HUMAN IMMUNODEFICIENCY VIRUS -- GENETIC ALGORITHM -- QUASISPECIES -- VIRUS INFECTION Аннотация: The aim of this work is the construction, calibration, and comparative analysis of mathematical models of the evolution of the human immunodeficiency virus (HIV) in the course of infection when the models are based on deterministic principles of the quasispecies theory (Eigen-Schuster) and on stochastic approaches of genetic algorithms (Holland). The models take into account the replication of viral genomes and selection of descendants according to their fitness, point mutations, multi-infection of target cells and recombination of genomes at the stage of formation of proviral DNA. The processes of diversification of the virus population under the action of the antiviral drug azidothymidine (AZT) that blocks reverse transcription of the virus are simulated. A four-letter alphabet is used in the stochasticmodel for description of nucleotide sequences. The parameters of the model are estimated using original data on the degree of adaptation of the HIV mutants that are partly or completely resistant to this drug. The influence of parameters of infection on the characteristics of viral mutants population diversity is studied \\\\expert2\\nbo\\Russian Journal of Numerical Anal. and Math. Modelling\\2015. V.30, N. 3. P. 157-170.pdf |
C 75 Consequences of the loss of microbial diversity in the human organism / V. A. Chereshnev, A. A. Morova, M. V. Chereshneva, G. V. Ikonnikova // Microbial Diversity: current situation, conservation strategy and ecological aspects «COMID 96»: International Conference: abstracts. - Perm, 1996. - P. 156 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): МИКРОБИОЛОГИЯ МЕДИЦИНСКАЯ -- МИКРОБИОЛОГИЯ МЕДИЦИНСКАЯ (ВЫЖИВАНИЕ БАКТЕРИЙ) |
T67 To preservation of the microbial biodiversity of a human organism / V. A. Chereshnev, A. A. Morova, M. V. Chereshneva, G. V. Ikonnikova // Microbial Diversity: current situation, conservation strategy and ecological aspects «COMID 96»: International Conference: abstracts. - Perm, 1996. - P. 156-157 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): МИКРОБИОЛОГИЯ МЕДИЦИНСКАЯ -- МИКРОБИОЛОГИЯ МЕДИЦИНСКАЯ (ВЫЖИВАНИЕ БАКТЕРИЙ) |
C 51 Chereshnev, V. A. Variable polyrhythmicity of processes in nature and society / V. A. Chereshnev, S. I. Stepanova, A. G. Gamburtsev // Herald of the Russian Academy of Sciences. - 2017. - Vol. 87, № 2. - P172-180. - Bibliogr. : p. 180 (15 ref.) Рубрики: ЕСТЕСТВЕННЫЕ НАУКИ--НАУКА ОБ ОКРУЖАЮЩЕЙ СРЕДЕ--ЭКОЛОГИЯ В ЦЕЛОМ--КОНФЕРЕНЦИИ ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): VARIABLE POLYRHYTHMICITY -- RHYTHMS IN NATURE AND SOCIETY -- TIME-SPECTRAL ANALYSIS Аннотация: The authors discuss possible causes of the variable polyrhythmicity of processes in nature and society, particularly in geophysics. It may be caused by desynchronization or resynchronization of processes that manifest themselves as a result of a shock impact on the geological environment, for example, in the form of an earthquake. Medical parameters are considered for which de- and resynchronization of rhythmic processes in the human organism are known, as well as geophysical processes, including underground noise of tidal origin and the seismicity of the Moon. \\\\expert2\\NBO\\Herald of the Russian Academy of Sciences\\2017. V. 87, N 2. P. 172-180.pdf |
Ч-46 Черешнев, Валерий Александрович. Оценка влияния бюджетных расходов на человеческое развитие регионов России / В. А. Черешнев, А. В. Васильева, А. Н. Тырсин // Экономика и предпринимательство. - 2016. - № 8. - С. 930-937 Рубрики: ЭКОНОМИКА. ЭКОНОМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): ИНДЕКС ЧЕЛОВЕЧЕСКОГО РАЗВИТИЯ -- HUMAN DEVELOPMENT INDEX -- БЮДЖЕТНЫЕ РАСХОДЫ -- BUDGET EXPENSES -- РЕГИОН -- REGION -- РЕГРЕССИОННЫЙ АНАЛИЗ -- REGRESSION ANALYSIS Аннотация: В статье анализируются особенности социально-экономического развития регионов России и отмечается их сильная дифференциация по уровню человеческого развития. Предложен и реализован подход к оценке количественной зависимости значения индекса человеческого развития от удельных (парциальных) бюджетных расходов субъектов РФ на основе корреляционно-регрессионного анализа. Сделан вывод о неэффективном расходовании бюджетных средств с позиции повышения региональных значений индекса человеческого развития. |
N 89 Novelties in the field of autoimmunity – 1st Saint Petersburg congress of autoimmunity, the bridge between east and west / Sh. Dahan, Y. Segal, A. Watad [et al.] // Autoimmunity Reviews. - 2017. - Vol. 16. - P1175-1184 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): AUTOIMMUNITY -- HUMAN PAPILLOMA VIRUS -- ALZHEIMER'S DISEASE -- INTRA VENOUS IMMUNOGLOBULINS -- PARANEOPLASTIC NEUROLOGICAL SYNDROME -- SYSTEMIC LUPUS ERYTHEMATOSUS -- ANTI-PHOSPHOLIPID SYNDROME \\\\Expert2\\NBO\\Autoimmunity Reviews\\2017 V. 16 P. 1175-1184.pdf |
Graph theory for modelling and analysis of the human lymphatic system / R. Savinkov, D. Grebennikov, D. Puchkova [et al.] // Mathematics. - 2020. - Vol. 8. - Ст. 2236. - 18 p. Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Кл.слова (ненормированные): ИММУНОЛОГИЯ -- СИСТЕМА ЛИМФАТИЧЕСКАЯ -- МОДЕЛИРОВАНИЕ МАТЕМАТИЧЕСКОЕ Аннотация: The human lymphatic system (HLS) is a complex network of lymphatic organs linked \\\\Expert2\\NBO\\Электрон. библиотека (Отеч.периодика)\\Черешнев В. А\\Mathematics 2020, 8, 2236.pdf |
Novel disease-associated missense single-nucleotide polymorphisms variants predication by algorithms tools and molecular dynamics simulation of human TCIRG1 gene causing congenital neutropenia and osteopetrosis / K. Shinwari, H. Rehman, H. Liu Guojun [et al.] // Frontiers in Molecular Biosciences. - 2022. - Vol. 9. - Ст. 879875 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ Аннотация: T Cell Immune Regulator 1, ATPase H + Transporting V0 Subunit A3 (TCIRG1 gene provides instructions for making one part, the a3 subunit, of a large protein complex known as a vacuolar H + -ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. Single amino acid changes in highly conserved areas of the TCIRG1 protein have been linked to autosomal recessive osteopetrosis and severe congenital neutropenia. We used multiple computational approaches to classify disease-prone single nucleotide polymorphisms (SNPs) in TCIRG1. We used molecular dynamics analysis to identify the deleterious nsSNPs, build mutant protein structures, and assess the impact of mutation. Our results show that fifteen nsSNPs (rs199902030, rs200149541, rs372499913, rs267605221, rs374941368, rs375717418, rs80008675, rs149792489, rs116675104, rs121908250, rs121908251, rs121908251, rs149792489 and rs116675104) variants are likely to be highly deleterious mutations as by incorporating them into wild protein they destabilize the wild protein structure and function. They are also located in the V-ATPase I domain, which may destabilize the structure and impair TCIRG1 protein activation, as well as reduce its ATPase effectiveness. These mutants have not yet been identified in patients suffering from CN and osteopetrosis while (G405R, R444L, and D517N) reported in our study are already associated with osteopetrosis. Mutation V52L reported in our study was identified in a patient suspected for CN. Finally, these mutants can help to further understand the broad pool of illness susceptibilities associated with TCIRG1 catalytic kinase domain activation and aid in the development of an effective treatment for associated diseases. |