45 research outputs found

    Regulation of Monoamine Oxidase A (MAO-A) Expression, Activity, and Function in IL-13–Stimulated Monocytes and A549 Lung Carcinoma Cells

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    Monoamine oxidase A (MAO-A) is a mitochondrial flavoen-zyme implicated in the pathogenesis of atherosclerosis and inflammation and also in many neurological disorders. MAO-A also has been reported as a potential therapeutic target in prostate cancer. However, the regulatory mechanisms controlling cytokine-induced MAO-A expression in immune or cancer cells remain to be identified. Here, we show that MAO-A expression is co-induced with 15-lipoxygenase (15-LO) in interleukin 13 (IL-13)-activated primary human monocytes and A549 nonsmall cell lung carcinoma cells. We present evidence that MAO-A gene expression and activity are regulated by signal transducer and activator of transcription 1, 3, and 6 (STAT1, STAT3, and STAT6), early growth response 1 (EGR1), and cAMP-responsive element– binding protein (CREB), the same transcription factors that control IL-13– dependent 15-LO expression. We further established that in both primary monocytes and in A549 cells, IL-13–stimulated MAO-A expression, activity, and function are directly governed by 15-LO. In contrast, IL-13– driven expression and activity of MAO-A was 15-LO–independent in U937 promonocytic cells. Furthermore, we demonstrate that the 15-LO– dependent transcriptional regulation of MAO-A in response to IL-13 stimulation in monocytes and in A549 cells is mediated by peroxisome proliferator–activated receptor (PPAR) and that signal transducer and activator of transcription 6 (STAT6) plays a crucial role in facilitating the transcriptional activity of PPAR. We further report that the IL-13–STAT6 – 15-LO–PPAR axis is critical for MAO-A expression, activity, and function, including migration and reactive oxygen species generation. Altogether, these results have major implications for the resolution of inflammation and indicat

    The northeastern Black Sea redox zone: Hydrochemical structure and its temporal variability

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    Detailed studies of the vertical structure of hydrochemical parameters in the northeastern Black Sea near Gelendzhik are presented and discussed. This work is based on a set of systematic observations carried out in this region during R/V Akvanavt and R/V Ashamba cruises from 1997 to 2005 and also on data from previous studies from 1984 to 1997. The Black Sea region near Gelendzhik is far from the influences of the Bosporus input and Danube River inflow. Therefore, the vertical structure in this region is more stable compared to the western Black Sea and reflects integrated, rather than local, changes of the Black Sea. Seasonal variations in the distribution of chemical parameters at the redox interface are connected to seasonal variations in hydrophysical processes and organic matter production. In winter, maxima of organic phosphorus and urea were absent in the vicinity of the onset of hydrogen sulfide. The concentrations of nitrate were lower in winter than in summer. Winter mixing in the anticyclone eddies led to reduced vertical gradients in the redox layer and to the disappearance of an upper phosphate minimum. Study of the interannual dynamics of oxygen concentrations in the Cold Intermediate Layer and anoxic waters boundary in the density field position revealed climatic-scale changes that may be connected with changes in the North Atlantic Oscillation (NAO) index. © 2006 Elsevier Ltd. All rights reserved

    Cognitive simulation as integrated innovative technology in teaching of social and humanitarian disciplines

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    © 2017 Authors. Currently, teachers are searching for innovative educational technologies that enhance the effectiveness of educational activities. The purpose of the paper is the development and approbation of cognitive simulation technology in teaching of social and humanitarian disciplines. Based on the integration of sources of innovation, the authors developed the technology of cognitive simulation aimed at the formation of a structured system of knowledge for social and humanitarian disciplines' subject area. Various forms of cognitive map methods used in the learning process (analysis, synthesis, projection, and simulation) allow developing the analytical and predictive abilities of students, and strengthening their educational motivation. The technology use is proposed for the first time for all socio-humanitarian disciplines in the process of vocational training, which contributes to the formation of inter-subject communications , spatial understanding of events, and transformations of reality. The empirical study carried out by the authors on the implementation of this technology in the educational process (the students of 3 universities, totaling 315 people participated in the study) confirmed the productivity of the technology and the possibility of its adaptation to various disciplines of social and humanitarian sphere

    Оценка адаптивной способности и стабильности сибирского генофонда фасоли овощной

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    Relevance. The evaluation of adaptive ability of varieties is an actual direction in selection. Phenotypic plasticity of legume crops, in particular green bean, in Siberian region has not been studied enough. There is a need to evaluate grade samples for adaptability and stability, as highly and medium adaptive varieties can realize their genetic potential of productivity in extreme continental climate of Western Siberia.Materials and methods. On the basis Department of Selection, Genetics and Forestry, Novosibirsk State Agrarian University (2015-2019), long-term evaluation of grade samples of green bean of different ecological and geographical origin with a bush type of growth was carried out. Of particular interest are signs that have a significant impact on crop productivity. The signs were studied: number of beans on plant, weight of beans from plant, weight of one bean, yield capacity. The objective of the study is to evaluate the adaptive ability and stability of common bean varieties in the conditions of Siberian region.Results. The conditions of Western Siberia are suitable for cultivating vegetable beans on a green spatula and seeds. It has been established that, based on the weight of one bean, the coefficient of variation has a negative value. This indicates a low variability of the trait depending on the natural and climatic conditions, which allows selection of breeding valuable varieties for this parameter. As a result of the study, 6 genotypes of the crop, combining high productivity and environmental resistance, were selected. It was established that varieties Veronika and Darina can be referred to non-plastic samples. Samples could diversify breeding material of the crop and show the value according to specific features in edaphic-climatic conditions of Western Siberia.Актуальность. Оценка адаптивного потенциала сортов является актуальным направлением в селекции. Главным условием для создания высококачественного сорта является сочетание в нем экологической пластичности и продуктивности. При этом большое внимание уделяется параметрам, оказывающим влияние на потенциальную продуктивность сорта. Экологическая пластичность зернобобовых культур, в частности фасоли овощной, недостаточно изучена в условиях Сибирского региона. Возникает необходимость оценки сортообразцов на адаптивность и стабильность, т.к. именно высоко- и среднеадаптивные сорта могут реализовать свой генетический потенциал продуктивности в резко-континентальном климате Западной Сибири.Материалы и методы. На кафедре селекции, генетики и лесоводства ФГБОУ ВО Новосибирский ГАУ проведена многолетняя оценка (2015-2019 года) сортообразцов фасоли овощной разного эколого-географического происхождения с кустовой формой растений. Особый интерес представляют признаки, оказывающие существенное влияние на продуктивность культуры. Изучены признаки: число бобов на растении, масса бобов с растения, масса боба, урожайность. Целью работы является оценка адаптивного потенциала и стабильности сортов фасоли обыкновенной в условиях Сибирского региона.Результаты. Условия Западной Сибири пригодны для возделывания фасоли овощной на зеленую лопатку и семена. Установлено, что по признаку «масса боба» коэффициент регрессии имеет отрицательное значение. Это свидетельствует о низкой вариабельности признака в зависимости от природно-климатических условий, что позволяет вести отбор селекционно-ценных сортов по данному параметру. Выделены 6 генотипов культуры, которые сочетают высокую продуктивность со средовой устойчивостью, благодаря которым можно разнообразить сибирский генофонд фасоли овощной

    Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

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    Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

    Leukocyte Integrin Mac-1 (CD11b/CD18,\u3csub\u3eM2\u3c/sub\u3e, CR3) Acts as a Functional Receptor for Platelet Factor 4

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    Platelet factor 4 (PF4) is one of the most abundant cationic proteins secreted from -granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (M2, CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner. The cell adhesion was partially blocked by anti-Mac-1 mAb and inhibition was enhanced when anti-Mac-1 antibodies were combined with glycosaminoglycans, suggesting that cell-surface proteoglycans act cooperatively with Mac-1. PF4 also induced Mac-1-dependent migration of human neutrophils and murine WT, but not Mac-1-deficient macrophages. Coating of Escherichia coli bacteria or latex beads with PF4 enhanced their phagocytosis by macrophages by 4-fold, and this process was blocked by different Mac-1 antagonists. Furthermore, PF4 potentiated phagocytosis by WT, but not Mac-1-deficient macrophages. As determined by biolayer interferometry, PF4 directly bound the MI-domain, the major ligand-binding region of Mac-1, and this interaction was governed by a Kd of 1.3 0.2 M. Using the PF4-derived peptide library, synthetic peptides duplicating the MI-domain recognition sequences and recombinant mutant PF4 fragments, the binding sites for MI-domain were identified in the PF4 segments Cys12–Ser26 and Ala57–Ser70. These results identify PF4 as a ligand for the integrin Mac-1 and suggest that many immune-modulating effects previously ascribed to PF4 are mediated through its interaction with Mac-1

    Evaluation of the adaptive ability and stability of the Siberian bean vegetable gene pool

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    Relevance. The evaluation of adaptive ability of varieties is an actual direction in selection. Phenotypic plasticity of legume crops, in particular green bean, in Siberian region has not been studied enough. There is a need to evaluate grade samples for adaptability and stability, as highly and medium adaptive varieties can realize their genetic potential of productivity in extreme continental climate of Western Siberia.Materials and methods. On the basis Department of Selection, Genetics and Forestry, Novosibirsk State Agrarian University (2015-2019), long-term evaluation of grade samples of green bean of different ecological and geographical origin with a bush type of growth was carried out. Of particular interest are signs that have a significant impact on crop productivity. The signs were studied: number of beans on plant, weight of beans from plant, weight of one bean, yield capacity. The objective of the study is to evaluate the adaptive ability and stability of common bean varieties in the conditions of Siberian region.Results. The conditions of Western Siberia are suitable for cultivating vegetable beans on a green spatula and seeds. It has been established that, based on the weight of one bean, the coefficient of variation has a negative value. This indicates a low variability of the trait depending on the natural and climatic conditions, which allows selection of breeding valuable varieties for this parameter. As a result of the study, 6 genotypes of the crop, combining high productivity and environmental resistance, were selected. It was established that varieties Veronika and Darina can be referred to non-plastic samples. Samples could diversify breeding material of the crop and show the value according to specific features in edaphic-climatic conditions of Western Siberia

    Studies on histones. 5. The histomes of the crocker sarcoma and spontaneous mammary tumours of mice.

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    © 2017 Authors. Currently, teachers are searching for innovative educational technologies that enhance the effectiveness of educational activities. The purpose of the paper is the development and approbation of cognitive simulation technology in teaching of social and humanitarian disciplines. Based on the integration of sources of innovation, the authors developed the technology of cognitive simulation aimed at the formation of a structured system of knowledge for social and humanitarian disciplines' subject area. Various forms of cognitive map methods used in the learning process (analysis, synthesis, projection, and simulation) allow developing the analytical and predictive abilities of students, and strengthening their educational motivation. The technology use is proposed for the first time for all socio-humanitarian disciplines in the process of vocational training, which contributes to the formation of inter-subject communications , spatial understanding of events, and transformations of reality. The empirical study carried out by the authors on the implementation of this technology in the educational process (the students of 3 universities, totaling 315 people participated in the study) confirmed the productivity of the technology and the possibility of its adaptation to various disciplines of social and humanitarian sphere
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