Federal Medical Biological Agency

Moscow, Russia

Federal Medical Biological Agency

Moscow, Russia
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Pashenkov M.V.,Federal Medical Biological Agency | Balyasova L.S.,Federal Medical Biological Agency | Dagil Y.A.,Federal Medical Biological Agency | Pinegin B.V.,Federal Medical Biological Agency
Journal of Immunology | Year: 2017

Activation of nucleotide-binding oligomerization domain (NOD) 1 and NOD2 by muropeptides triggers a complex transcriptional program in innate immune cells. However, little is known about posttranscriptional regulation of NOD1- and NOD2-dependent responses. When stimulated with a prototypic NOD1 agonist, N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamylmeso- diaminopimelic acid (GM-triDAP), human monocyte-derived macrophages (MDM) produced an order of magnitude more TNF, IL-6, and pro-IL-1β than did monocyte-derived dendritic cells (MDDC), despite similar NOD1 expression, similar cytokine mRNA kinetics, and comparable responses to LPS. TNF production by GM-triDAP-activated MDM was independent of autocrine IL-1. However, GM-triDAP-activated MDM translated TNF mRNA more efficiently than did MDDC. As an underlying mechanism, NOD1 triggering in MDM caused a more potent and long-lasting activation of the signaling axis involving p38 MAPK, MAPK-interacting kinase (MNK), and eukaryotic translation initiation factor 4E, which is a critical regulator of translation. Furthermore, MNK controlled TNF mRNA abundance in MDDC and MDM upon NOD1 triggering. NOD1-dependent responses were more sensitive to MNK inhibition than were TLR4-dependent responses. These results demonstrate the importance of the p38-MNK-eukaryotic translation initiation factor 4E axis in TNF production downstream of NOD1. Copyright © 2017 by The American Association of Immunologists, Inc.


Kostinov M.P.,Moscow State University | Kostinova A.M.,Federal Medical Biological Agency
Pediatriya - Zhurnal im G.N. Speranskogo | Year: 2017

The literature review contains research materials proving the safety and immunogenicity of modern combined vaccines, especially those containing pertussis, and facts that disprove myths about their negative impact on the children development. Presented data can broad the view on the active use of combination vaccines in health care practice. © 2017, Pediatria Ltd. All rights reserved.


Khvostunov I.K.,Medical Radiological Research Center | Sevan'Kaev A.V.,Medical Radiological Research Center | Lloyd D.C.,Public Health England | Nugis V.Y.,Federal Medical Biological Agency | Voisin P.,Institute for Radiological Protection and Nuclear Safety
Radiation Measurements | Year: 2011

This paper considers how well standard calibration curve for translocations constructed for lymphocyte cultures irradiated in vitro with gamma-rays from 60Co compares with the translocations yield in lymphocytes taken from people at a long post-exposure time. Data were used from radiation accident victims overexposed to doses ranging from 0.2 to 8.5 Gy and who were cytogenetically followed-up for various times upto 50 y. Their cultured lymphocytes had been scored both by the conventional dicentric method and by FISH for all translocations involving painted chromosomes (2, 3, 8); (2, 3, 5) or (2, 4, 12). The in vivo dose response relationship was derived by fitting translocation frequencies to the contemporary individual doses obtained independently and confirmed by different biological assays and physical dosimetry. A comparison with the conventional in vitro curve indicates reductions of translocation frequencies with increasing time which would prejudice retrospective dose assessment by FISH. This has led to the possibility to amend the in vitro dose response curve for translocations to make it more suitable for use in retrospective biodosimetry. This approach for retrospective biodosimetry therefore uses a dose response relationship based on truly persisting translocations. © 2011 Elsevier Ltd. All rights reserved.


Bouville A.,U.S. National Cancer Institute | Kryuchkov V.,Federal Medical Biological Agency
Health Physics | Year: 2014

The increased occupational doses resulting from the Chernobyl nuclear reactor accident that occurred in Ukraine in April 1986, the reactor accident of Fukushima that took place in Japan in March 2011, and the early operations of the Mayak Production Association in Russia in the 1940s and 1950s are presented and discussed. For comparison purposes, the occupational doses due to the other two major reactor accidents (Windscale in the United Kingdom in 1957 and Three Mile Island in the United States in 1979) and to the main plutonium-producing facility in the United States (Hanford Works) are also covered but in less detail. Both for the Chernobyl nuclear reactor accident and the routine operations at Mayak, the considerable efforts made to reconstruct individual doses from external irradiation to a large number of workers revealed that the recorded doses had been overestimated by a factor of about two. © 2014 Health Physics Society.


Vorobjeva N.V.,Moscow State University | Pinegin B.V.,Federal Medical Biological Agency
Immunobiology | Year: 2015

Neutrophils can entrap and kill pathogens by releasing of neutrophil extracellular traps (NETs), in addition to their routine functions such as phagocytosis and degranulation. NETs consist of a DNA backbone supplemented by multiple bactericidal proteins from the nucleus, the cytoplasm and the granules. Neutrophils release NETs after their activation by a number of physiological and pharmacological stimuli. In addition to the antimicrobial function, NETs are involved in the pathogenesis of various autoimmune and inflammatory diseases. Since NET formation predominantly depends on the generation of reactive oxygen species (ROS), all substances that are capable of scavenging ROS or inhibiting the enzymes responsible for their synthesis should prevent ROS-associated NET release. The aim of this study was to test substances with an antioxidant activity, such as Trolox, Tiron, and Tempol, for their capacity to inhibit NET formation by primary human neutrophils in vitro. We revealed for the first time an inhibitory effect of Trolox on ROS-dependent NET release. We also established a suppressive effect of Tempol on NET formation that manifested itself in a wide range of concentrations. In this study, no inhibitory influence of Tiron on NET release was revealed. All tested substances exerted a significant dose-dependent antioxidative effect on ROS generation induced by phorbol 12-myristate 13-acetate (PMA). We suggest that the antioxidants Trolox and Tempol should be recommended for treating autoimmune and inflammatory diseases that implicate ROS-dependent NET release. © 2015 Elsevier GmbH.


Krasnov K.A.,Federal Medical Biological Agency | Kartsev V.G.,InterBioScreen Ltd. | Khrustalev V.N.,RAS Nesmeyanov Institute of Organoelement Compounds
Tetrahedron | Year: 2010

Knoevenagel products formed by the condensation of N-monoalkyl barbituric acids with o-tert-amino benzaldehydes undergo tert-amino effect reactions (T-reactions) yielding 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′- (1′,2′,3′,4′-tetrahydroquinoline) derivatives as a mixture of (S*,S*)- and (S*,R*)-diastereomers. Mostly, the major diastereomer has the S*,S*-configuration. According to X-ray diffraction data in the solid form and NOE data in solution, diastereoselectivity of the T-reactions can be associated with the structure of the Knoevenagel products whose conformation is fixed by the strong intramolecular C-H⋯π interaction. © 2010 Elsevier Ltd. All rights reserved.


Safonova T.N.,RAS A.N. Bach Institute of Biochemistry | Mikhailov S.N.,RAS Engelhardt Institute of Molecular Biology | Veiko V.P.,RAS A.N. Bach Institute of Biochemistry | Mordkovich N.N.,RAS A.N. Bach Institute of Biochemistry | And 5 more authors.
Acta Crystallographica Section D: Biological Crystallography | Year: 2014

Uridine phosphorylase (UP; EC 2.4.2.3), a key enzyme in the pyrimidine-salvage pathway, catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate. Expression of UP from Shewanella oneidensis MR-1 (SoUP) was performed in Escherichia coli. The high-resolution X-ray structure of SoUP was solved in the free form and in complex with uridine. A crystal of SoUP in the free form was grown under microgravity and diffracted to ultrahigh resolution. Both forms of SoUP contained sulfate instead of phosphate in the active site owing to the presence of ammonium sulfate in the crystallization solution. The latter can be considered as a good mimic of phosphate. In the complex, uridine adopts a high-syn conformation with a nearly planar ribose ring and is present only in one subunit of the hexamer. A comparison of the structures of SoUP in the free form and in complex with the natural substrate uridine showed that the subunits of the hexamer are not identical, with the active sites having either an open or a closed conformation. In the monomers with the closed conformation, the active sites in which uridine is absent contain a glycerol molecule mimicking the ribose moiety of uridine. © 2014 International Union of Crystallography.


Pinegin B.,Federal Medical Biological Agency | Vorobjeva N.,Moscow State University | Pinegin V.,Moscow State University
Autoimmunity Reviews | Year: 2015

The pathogenesis of many autoimmune diseases is initially based on a redundant or prolonged activation of the innate immune system. It was suggested that an excessive activation of the innate immunity is often the result of a chronic inflammatory process in the organism. This inflammation can be induced by exogenous and endogenous alarm factors, or alarmins. We believe that the recently discovered neutrophil extracellular traps, or NETs, completely meet the criteria of alarmins. This review summarizes current knowledge concerning the general characteristics of NETs, their antimicrobial properties, and their role in the development of chronic inflammatory processes that underlie the pathogenesis of psoriasis and atherosclerosis. Studies on the NETosis can provide the foundation for developing new diagnostic methods and effective treatment of chronic inflammatory and autoimmune diseases. © 2015 Elsevier B.V.


Gustyleva L.K.,Federal Medical Biological Agency | Savel'Eva E.I.,Federal Medical Biological Agency
Russian Journal of General Chemistry | Year: 2014

Method was developed for detection of residual amounts of Russian toxic agent RVX on metallic surface. The method is based on RVX conversion into O-isobutyl ester of methylphosphonic acid fluoride on a filter impregnated with silver fluoride, followed by detection of the formed derivative using a flame photometer. The method sensitivity has been enhanced by application of a large volume injection (0.20 mL). The method allows determination of RVX levels corresponding to the sanitary regulations and is intended for control measures at the toxic agents elimination establishments and for determination of the Danger grade of metallic waste. © Pleiades Publishing, Ltd., 2014. Original Russian Text © L.K. Gustyleva, E.I. Savel'eva, 2014.


Osipov A.N.,RAS Semenov Institute of Chemical Physics | Smetanina N.M.,Federal Medical Biological Agency | Pustovalova M.V.,Federal Medical Biological Agency | Arkhangelskaya E.,RAS Semenov Institute of Chemical Physics | Klokov D.,Chalk River Laboratories
Free Radical Biology and Medicine | Year: 2014

The potency of UVA radiation, representing 90% of solar UV light reaching the earths surface, to induce human skin cancer is the subject of continuing controversy. This study was undertaken to investigate the role of reactive oxygen species in DNA damage produced by the exposure of human cells to UVA radiation. This knowledge is important for better understanding of UV-induced carcinogenesis. We measured DNA single-strand breaks and alkali-labile sites in human lymphocytes exposed ex vivo to various doses of 365-nm UV photons compared to X-rays and hydrogen peroxide using the comet assay. We demonstrated that the UVA-induced DNA damage increased in a linear dose-dependent manner. The rate of DNA single-strand breaks and alkali-labile sites after exposure to 1 J/cm 2 was similar to the rate induced by exposure to 1 Gy of X-rays or 25 μM hydrogen peroxide. The presence of either the hydroxyl radical scavenger dimethyl sulfoxide or the singlet oxygen quencher sodium azide resulted in a significant reduction in the UVA-induced DNA damage, suggesting a role for these reactive oxygen species in mediating UVA-induced DNA single-strand breaks and alkali-labile sites. We also showed that chromatin relaxation due to hypertonic conditions resulted in increased damage in both untreated and UVA-treated cells. The effect was the most significant in the presence of 0.5 M Na+, implying a role for histone H1. Our data suggest that the majority of DNA single-strand breaks and alkali-labile sites after exposure of human lymphocytes to UVA are produced by reactive oxygen species (the hydroxyl radical and singlet oxygen) and that the state of chromatin may substantially contribute to the outcome of such exposures. © 2014 Elsevier Inc. All rights reserved.

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