ГЕОДИНАМИЧЕСКАЯ МОДЕЛЬ ВЗАИМОДЕЙСТВИЯ ЗОНЫ СУБДУКЦИИ С КОНТИНЕНТАЛЬНОЙ ЛИТОСФЕРОЙ В ОБЛАСТИ ПЕРЕХОДА ОТ ТИХОГО ОКЕАНА К ВОСТОЧНОЙ АЗИИ

East Asia is the vast region of Asia which is characterized by a complex geological structure and high activity of seismic and tectonic processes. Satellite geodetic data, reflecting the recent crustal movements in the region, demonstrate a considerable variability in magnitude and direction of motions both along the strike of island-arc margins and deep into the continent. To explain the anomalies in the Earth's surface displacement field, the paper proposes a geodynamic model of East Asia which involves the mechanism of interaction between the continental lithosphere of the region and the continent-to-ocean transition area along the Kuril-Kamchatka and Japanese island arcs. The proposed concept includes the model of the upper-mantle convective cell, developing beneath the continental lithosphere, in combination with the keyboard-block model explaining the regularities of seismic cycle in the island-arc margins. It has been shown that the consideration of interaction between the lithosphere and upper mantle in the continent-to-ocean transition area in the framework of the model of non-stationary convective cell allows us to explain the recent crustal movements observed up to a distance of 2000 km and the seismic tomography data without involving additional lithospheric blocks. The model contributes to the development of the physically grounded geodynamic approach to the analysis of recent tectonics and eliminates the inconsistencies between the observed data and classical plate tectonics in East Asia.Регион Восточной Азии характеризуется сложным геологическим строением и высокой сейсмической и тектонической активностью. Данные спутниковой геодезии, отражающие современные движения земной поверхности региона, демонстрируют существенную изменчивость по величине и направлению как вдоль простирания островодужных окраин, так и в глубь континента. В работе для объяснения аномалий поля смещений земной поверхности предлагается геодинамическая модель Восточной Азии, учитывающая механизм взаимодействия континентальной литосферы региона и переходной зоны континент – океан вдоль Курило-Камчатской и Японской островных дуг. Представленная концепция включает в себя модель верхнемантийной конвективной ячейки, развивающейся под континентальной литосферой, в сочетании с клавишно-блоковой моделью, объясняющей закономерности сейсмического цикла в островодужных окраинах. Показано, что учет взаимодействия литосферы и верхней мантии в зоне перехода континент – океан позволяет в рамках модели нестационарной конвективной ячейки объяснить наблюдающиеся на удалении до 2000 км современные движения земной поверхности и данные сейсмической томографии без привлечения дополнительных литосферных блоков. Модель способствует развитию физически обоснованного геодинамического подхода к анализу современной тектоники и позволяет устранить противоречия между наблюдаемыми данными и классической тектоникой плит в регионе Восточной Азии

Hepatitis C Virus Sensitizes Host Cells to TRAIL-Induced Apoptosis by Up-Regulating DR4 and DR5 via a MEK1-Dependent Pathway

BACKGROUND: Hepatitis C virus (HCV) is the leading cause of liver fibrosis, cirrhosis and hepatocellular carcinoma. It is believed that continuous liver cell apoptosis contributes to HCV pathogenesis. Recent studies have shown that HCV infection can sensitize host cells to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis, but the mechanism by which HCV regulates the TRAIL pathway remains unclear. METHODS AND RESULTS: Using a sub-genomic replicon and full length virus, JFH-1, we demonstrate that HCV can sensitize host cells to TRAIL-induced apoptosis by up-regulating two TRAIL receptors, death receptor 4 (DR4) and death receptor 5 (DR5). Furthermore, the HCV replicon enhanced transcription of DR5 via Sp1, and the HCV-mediated up-regulation of DR4 and DR5 required MEK1 activity. HCV infection also stimulated the activity of MEK1, and the inhibition of MEK1 activity or the knockdown of MEK1 increased the replication of HCV. CONCLUSIONS: Our studies demonstrate that HCV replication sensitizes host cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5 via a MEK1 dependent pathway. These findings may help to further understand the pathogenesis of HCV infection and provide a therapeutic target

Plasmacytoid Dendritic Cells Capture and Cross-Present Viral Antigens from Influenza-Virus Exposed Cells

Among the different subsets of dendritic cells (DC), plasmacytoid dendritic cells (PDC) play a unique role in secreting large amounts of type I interferons upon viral stimulation, but their efficiency as antigen-presenting cells has not been completely characterized. We show here, by flow cytometry, with human primary blood PDC and with a PDC cell line, that PDC display poor endocytic capacity for soluble or cellular antigens when compared to monocyte-derived myeloid DC. However, immature PDC efficiently take up cellular material from live influenza-exposed cells, subsequently mature and cross-present viral antigens very efficiently to specific CD8+ T cells. Therefore, during viral infection PDC not only secrete immunomodulatory cytokines, but also recognize infected cells and function as antigen cross-presenting cells to trigger the anti-viral immune response

Protein Phosphatase-1 Activates CDK9 by Dephosphorylating Ser175

The cyclin-dependent kinase CDK9/cyclin T1 induces HIV-1 transcription by phosphorylating the carboxyterminal domain (CTD) of RNA polymerase II (RNAPII). CDK9 activity is regulated by protein phosphatase-1 (PP1) which was previously shown to dephosphorylate CDK9 Thr186. Here, we analyzed the effect of PP1 on RNAPII phosphorylation and CDK9 activity. The selective inhibition of PP1 by okadaic acid and by NIPP1 inhibited phosphorylation of RNAPII CTD in vitro and in vivo. Expression of the central domain of NIPP1 in cultured cells inhibited the enzymatic activity of CDK9 suggesting its activation by PP1. Comparison of dephosphorylation of CDK9 phosphorylated by (32P) in vivo and dephosphorylation of CDK9's Thr186 analyzed by Thr186 phospho-specific antibodies, indicated that a residue other than Thr186 might be dephosphorylated by PP1. Analysis of dephosphorylation of phosphorylated peptides derived from CDK9's T-loop suggested that PP1 dephosphorylates CDK9 Ser175. In cultured cells, CDK9 was found to be phosphorylated on Ser175 as determined by combination of Hunter 2D peptide mapping and LC-MS analysis. CDK9 S175A mutant was active and S175D – inactive, and dephosphorylation of CDK9's Ser175 upregulated HIV-1 transcription in PP1-dependent manner. Collectively, our results point to CDK9 Ser175 as novel PP1-regulatory site which dephosphorylation upregulates CDK9 activity and contribute to the activation of HIV-1 transcription

Plasmacytoid Dendritic Cells Capture and Cross-Present Viral Antigens from Influenza-Virus Exposed Cells

Among the different subsets of dendritic cells (DC), plasmacytoid dendritic cells (PDC) play a unique role in secreting large amounts of type I interferons upon viral stimulation, but their efficiency as antigen-presenting cells has not been completely characterized. We show here, by flow cytometry, with human primary blood PDC and with a PDC cell line, that PDC display poor endocytic capacity for soluble or cellular antigens when compared to monocyte-derived myeloid DC. However, immature PDC efficiently take up cellular material from live influenza-exposed cells, subsequently mature and cross-present viral antigens very efficiently to specific CD8+ T cells. Therefore, during viral infection PDC not only secrete immunomodulatory cytokines, but also recognize infected cells and function as antigen cross-presenting cells to trigger the anti-viral immune response

The effector T cell response to influenza infection

Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs

CLUSTER PROJECT: CONCEPTS, TYPOLOGY AND MODELING APPROACHES

In the article we considered the existing understanding of the relationship between the concepts of cluster policy, cluster program and cluster project, defined special features of cluster projects, and then developed our own definition of cluster project. Basic characteristics of industrial (vertical) and regional (horizontal) clusters were discussed. Then we distinguished three types of cluster projects and their main characteristics in horizontal clusters. The nature and features of competition and cooperation, their main types and forms were overviewed. We made hypotheses about factors that influence competition and cooperation. We described some already existing approaches to competition and cooperation modeling and their possible problems. Specific characteristics of agents in multi-agent system were defined. Conceptual agent-based model of competition and cooperation interactions between the members of the cluster project was proposed