Screening studies of POP levels in bottom sediments from selected lakes in the Paz watercourse

Appendix 5/15 of the publication "State of the environment in the Norwegian, Finnish and Russian border area 2007" (The Finnish Environment 6/2007)

Screening studies of POP levels in fish from selected lakes in the Paz watercourse

Appendix 8/15 of the publication "State of the environment in the Norwegian, Finnish and Russian border area 2007" (The Finnish Environment 6/2007)

Investigation of 5’-norcarbocyclic nucleoside analogues as antiprotozoal and antibacterial agents

Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories from two structurally related scaffolds have shown promising activity against both Mycobacterium tuberculosis and several parasitic strains. As a result, a small structure activity relationship study was designed to further probe their activity and potential. Their synthesis and the results of the subsequent biological activity are reported herein

HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist

Funding Information: https://orcid.org/0000-0002-6160-2203 Bayurova Ekaterina [email protected] 1 2 Jansons Juris [email protected] 3 4 Skrastina Dace [email protected] 3 4 https://orcid.org/0000-0002-4980-9754 Smirnova Olga [email protected] 5 Mezale Dzeina [email protected] 3 Kostyusheva Anastasia [email protected] 6 Kostyushev Dmitry [email protected] 6 Petkov Stefan [email protected] 7 Podschwadt Philip [email protected] 7 https://orcid.org/0000-0003-0365-570X Valuev-Elliston Vladimir [email protected] 5 Sasinovich Sviataslau [email protected] 7 https://orcid.org/0000-0003-2278-4451 Korolev Sergey [email protected] 8 Warholm Per [email protected] 9 https://orcid.org/0000-0002-2260-6551 Latanova Anastasia [email protected] 1 5 https://orcid.org/0000-0003-2183-0858 Starodubova Elizaveta [email protected] 1 5 https://orcid.org/0000-0001-8506-2339 Tukhvatulin Amir [email protected] 1 Latyshev Oleg [email protected] 1 Selimov Renat [email protected] 10 Metalnikov Pavel [email protected] 10 Komarov Alexander [email protected] 10 https://orcid.org/0000-0002-3673-4714 Ivanova Olga [email protected] 5 Gorodnicheva Tatiana [email protected] 11 https://orcid.org/0000-0002-7443-6961 Kochetkov Sergey [email protected] 5 Gottikh Marina [email protected] 8 Strumfa Ilze [email protected] 3 https://orcid.org/0000-0002-5659-9679 Ivanov Alexander [email protected] 5 Gordeychuk Ilya [email protected] 1 2 12 https://orcid.org/0000-0001-9382-2254 Isaguliants Maria [email protected] 1 2 3 7 García-Rivas Gerardo 1 NF Gamaleya Research Center of Epidemiology and Microbiology Moscow Russia 2 Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences Moscow Russia chumakovs.ru 3 Department of Pathology Riga Stradins University Riga Latvia rsu.lv 4 Latvian Biomedical Research and Study Centre Riga Latvia lu.lv 5 Engelhardt Institute of Molecular Biology Russian Academy of Sciences Moscow Russia ras.ru 6 National Medical Research Center for Tuberculosis and Infectious Diseases Moscow Russia 7 Department of Microbiology Tumor and Cell Biology Karolinska Institutet Stockholm Sweden ki.se 8 Chemistry Department and Belozersky Institute of Physico-Chemical Biology Lomonosov Moscow State University Moscow Russia msu.ru 9 Science for Life Laboratory Stockholm University Stockholm Sweden su.se 10 Russian State Center for Quality and Standardization of Veterinary Drugs and Feed (VGNKI) Moscow Russia 11 Evrogen Moscow Russia 12 Sechenov First Moscow State Medical University Moscow Russia mma.ru 2019 2 12 2019 2019 08 05 2019 01 11 2019 05 11 2019 2 12 2019 2019 Copyright © 2019 Ekaterina Bayurova et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. HIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk of “non-AIDS-defining” malignancies not directly linked to immune suppression but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones of murine mammary gland adenocarcinoma 4T1luc2 cells expressing consensus reverse transcriptase of HIV-1 subtype A FSU_A strain (RT_A) with and without primary mutations of drug resistance. In in vitro tests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. Expression of these RT_A variants in 4T1luc2 cells led to increased production of the reactive oxygen species (ROS), lipid peroxidation, enhanced cell motility in the wound healing assay, and upregulation of expression of Vimentin and Twist . These properties, particularly, the expression of Twist , correlated with the levels of expression RT_A and/or the production of ROS. When implanted into syngeneic BALB/C mice, 4T1luc2 cells expressing nonmutated RT_A demonstrated enhanced rate of tumor growth and increased metastatic activity, dependent on the level of expression of RT_A and Twist . No enhancement was observed for the clones expressing mutated RT_A variants. Plausible mechanisms are discussed involving differential interactions of mutated and nonmutated RTs with its cellular partners involved in the regulation of ROS. This study establishes links between the expression of HIV-1 RT, production of ROS, induction of EMT, and enhanced propagation of RT-expressing tumor cells. Such scenario can be proposed as one of the mechanisms of HIV-induced/enhanced carcinogenesis not associated with immune suppression. Ministry of Science and Higher Education of the Russian Federation 075-15-2019-1660 Latvian Science Council LZP-2018/2-0308 EU VACTRAIN Russian Foundation for Basic Research 17-00-00085 17_04_00583 17_54_30002 Publisher Copyright: © 2019 Ekaterina Bayurova et al.HIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk of "non-AIDS-defining" malignancies not directly linked to immune suppression but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones of murine mammary gland adenocarcinoma 4T1luc2 cells expressing consensus reverse transcriptase of HIV-1 subtype A FSU_A strain (RT_A) with and without primary mutations of drug resistance. In in vitro tests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. Expression of these RT_A variants in 4T1luc2 cells led to increased production of the reactive oxygen species (ROS), lipid peroxidation, enhanced cell motility in the wound healing assay, and upregulation of expression of Vimentin and Twist. These properties, particularly, the expression of Twist, correlated with the levels of expression RT_A and/or the production of ROS. When implanted into syngeneic BALB/C mice, 4T1luc2 cells expressing nonmutated RT_A demonstrated enhanced rate of tumor growth and increased metastatic activity, dependent on the level of expression of RT_A and Twist. No enhancement was observed for the clones expressing mutated RT_A variants. Plausible mechanisms are discussed involving differential interactions of mutated and nonmutated RTs with its cellular partners involved in the regulation of ROS. This study establishes links between the expression of HIV-1 RT, production of ROS, induction of EMT, and enhanced propagation of RT-expressing tumor cells. Such scenario can be proposed as one of the mechanisms of HIV-induced/enhanced carcinogenesis not associated with immune suppression.publishersversionPeer reviewe

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity

Unified Hierarchical Model of the Data Exchange

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала.The paper presents an approach to standardized data exchange between heterogeneous resources based on a unified hierarchical model of the data representation. The paper gives a metamodel and description of the structural elements of the unified model. Some conversion algorithms were developed to turn the information storage schemes into the unified hierarchical model in the case of XML-format

Mathematical models of MOS transistors with induced and ion-doped conditions in energy engineering

Mathematical models of integrated circuit (IC) elements are one of the foundations in energy engineering in setting and solving IC design problems. When developing an IC, its elements and the circuit itself are created simultaneously, so the IC developer’s natural desire is to use models of elements relative to structural parameters, which makes it possible to analyze and optimize the characteristics of the IC before producing trial batches. To date, a number of Metal Oxide-Semiconductor (MOS) transistor models have been developed regarding structural parameters, but their use, as a rule, does not provide acceptable analysis accuracy and in some cases leads to unnecessary computer time consumption, which is explained by their complexity. The issue of creating mathematical models of MOS transistors and IL-channels, which have found wide application in the creation of integrated circuits, is especially acute, but simple and, at the same time, sufficiently accurate mathematical models have not been created to date. Therefore, the main goal of this chapter is to conduct a comparative analysis of existing models of MOS transistors with induced and ion-doped channels and develop models that largely eliminate the shortcomings of the existing ones. The issues of determining the electrical parameters of MIS structures are also considered and experimental results of studying the accuracy of the developed models are presented